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Sciatic nerve symptomatology may arise from both intra- and extra-neural pathology, at any point along descent from the sacral plexus to its bifurcation. The potential aetiology is broad, ranging from degenerative spinal disease to muscle, bony and vascular pathology. We present an extremely unusual case of position and exercise-induced nerve compression secondary to arteriovenous malformation and review the potential extraspinal causes, many of which may be ameliorated by surgical excision or decompression. We further discuss the usefulness of diagnostic imaging, specific clinical tests and histopathological tools that may aid in management.

Cardiac arrhythmia has been defined as one of the abnormal heart rhythm symptoms, which is a common problem dealt with by cardiologists. Zebrafish were established as a powerful animal model with a transparent body that enables optical observation to analyze cardiac morphology and cardiac rhythm regularity. Currently, research has observed heart-related parameters in zebrafish, which used different approaches, such as starting from the use of fluorescent transgenic zebrafish, different software, and different observation methods. In this study, we developed an innovative approach by using the OpenCV library to measure zebrafish larvae heart rate and rhythm. The program is designed in Python, with the feature of multiprocessing for simultaneous region-of-interest (ROI) detection, covering both the atrium and ventricle regions in the video, and was designed to be simple and user-friendly, having utility even for users who are unfamiliar with Python. Results were validated with our previously published method using ImageJ, which observes pixel changes. In summary, the results showed good consistency in heart rate-related parameters. In addition, the established method in this study also can be widely applied to other invertebrates (like Daphnia) for cardiac rhythm measurement.

The burden of type 2 diabetes and related complications has steadily increased over the last few decades and is one of the foremost global public health threats in the 21st century. Diabetes is one of the leading causes of chronic kidney disease and kidney failure and is an important contributor to the cardiovascular morbidity and mortality in this population. In addition, up to one in three patients who have received kidney transplants develop post-transplant diabetes, but the management of this common complication continues to pose a significant challenge for clinicians. In this review, we will describe the global prevalence and temporal trend of kidney failure attributed to diabetes mellitus in both developing and developed countries. We will examine the survival differences between treated kidney failure patients with and without type 2 diabetes, focusing on the survival differences in those on maintenance dialysis or have received kidney transplants. With the increased availability of novel hypoglycemic agents, we will address the potential impacts of these novel agents in patients with diabetes and kidney failure and in those who have developed post-transplant diabetes.

The revolution in the digital economy is forcing the manufacturing industry to develop new business models to achieve operational excellence. Vendor Management Inventory (VMI) is a key measure, aim...

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including causing abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that chronic waterborne exposure to DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases of reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that the chronic waterborne exposure of DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.

The heart is the most important muscular organ of the cardiovascular system, which pumps blood and circulates, supplying oxygen and nutrients to peripheral tissues. Zebrafish have been widely explored in cardiotoxicity research. For example, the zebrafish embryo has been used as a human heart model due to its body transparency, surviving several days without circulation, and facilitating mutant identification to recapitulate human diseases. On the other hand, adult zebrafish can exhibit the amazing regenerative heart muscle capacity, while adult mammalian hearts lack this potential. This review paper offers a brief description of the major methodologies used to detect zebrafish cardiac rhythm at both embryonic and adult stages. The dynamic pixel change method was mostly performed for the embryonic stage. Other techniques, such as kymography, laser confocal microscopy, artificial intelligence, and electrocardiography (ECG) have also been applied to study heartbeat in zebrafish embryos. Nevertheless, ECG is widely used for heartbeat detection in adult zebrafish since ECG waveforms’ similarity between zebrafish and humans is prominent. High-frequency ultrasound imaging (echocardiography) and modern electronic sensor tag also have been proposed. Despite the fact that each method has its benefits and limitations, it is proved that zebrafish have become a promising animal model for human cardiovascular disease, drug pharmaceutical, and toxicological research. Using those tools, we conclude that zebrafish behaviors as an excellent small animal model to perform real-time monitoring for the developmental heart process with transparent body appearance, to conduct the in vivo cardiovascular performance and gene function assays, as well as to perform high-throughput/high content drug screening.

Background ANCA-associated vasculitis (AAV) is more prevalent in rural Australia compared to metropolitan areas suggesting a role of environment in disease pathogenesis. However, the prevalence of environmental risk factors in Australian AAV patients has not been described. Aims To compare the incidence of AAV between two health districts (Illawarra Shoalhaven local health district (ISLHD), a mixed rural/metropolitan region, and South Eastern Sydney local health district (SESLHD), a metropolitan region) in Australia and its relationship to environmental exposures. Methods Cases of AAV from 2002 to 2017 were retrospectively identified from ISLHD and SESLHD using electronic medical records. Eligible participants were invited to complete a standardised questionnaire examining their exposure to silica, solvents, metal, dust, farming, gardening, and sunlight. Results 156 cases of AAV were identified from 2002 to 2017. A higher cumulative incidence of AAV was observed in the ISLHD (184.2 [95% confidence interval (CI) 143.6-232.7] per million) compared to SESLHD (102.6 [95% CI 82.1-126.8] per million). Over 50% of the cohort had high levels of silica and solvents exposure, based on self-reported questionnaires. There was no significant relationship between region and exposure to silica (p=0.96), solvents (p=0.44), metal (p=0.33), dust (p=0.25), farming (p=0.90), gardening (p=0.93), or sunlight (p=0.55). Conclusions We found a higher incidence of AAV in ISLHD compared to SESLHD with high levels of exposure to silica and solvents in both regions based on self-reported questionnaires. Prospective systematic collection of data, such as a registry of AAV, is warranted to further explore the relationship between environmental exposures and AAV. This article is protected by copyright. All rights reserved.

Background Renal replacement therapy (RRT) places a burden on patients, and geographical relocation for easier access to healthcare facilities is a necessity for some. Incidence and factors associated with relocation has not been comprehensively examined at a national level. We aimed to determine proportion, incidence, characteristics of RRT patients who relocate and relocation rate by remoteness of residence and dialysis modality. Methods Retrospective cohort analysis using Australian and New Zealand Dialysis and Transplant Registry to examine RRT patients in Australia from January 2005 to December 2015. Relocation incidence was calculated for remoteness of residence and RRT modality as rate per 100 patient years. Factors associated with relocation were examined using competing risk regression models with death as a competing event. Results Of 24,676 incident patients on RRT, 5888 (23.9%) relocated with a median time of 1.6 years [IQR 0.7–3.4] years. Relocation incidence was 7.9 per 100 patient years and increased from major cities to very remote regions (7.2 to 48.8 per 100 patient years respectively, p p = 0.034) and very remote regions (SHR 3.51 95% 3.05, 4.04 p p = 0.002) while transplant patients were less likely to relocate compared to haemodialysis patients (HR 0.37, 95%CI 0.34, 0.39, p Conclusions Relocation in patients receiving RRT is associated with remoteness of residence, RRT modality and ethnicity. Reasons for relocation and its impact on patient wellbeing and outcome should be further explored.

This paper presents the design of a collimator lens for use with the Lightbrick that uses total internal reflection as well as convex and concave surfaces. The Lightbrick is a light collector for the Natural Light Illumination System. The collimator lens is constructed using freeform surfaces which can be calculated through geometric-optics. Verified by optical simulation, using the collimator lens can achieve 90.3% luminous flux within ±2°, and optical efficiency improves by 48% in the collimator lens output. The collimator lens converges the light distribution of the Lightbrick and enhances the transmission efficiency of the Natural Light Illumination System.

Aim After extended left colectomy, traditional colorectal anastomosis is often not feasible because of insufficient length of the remaining colon to perform a tension-free anastomosis. Total colectomy with ileorectal anastomosis could be an alternative but this can lead to unsatisfactory quality of life. Trans-mesenteric colorectal anastomosis or inverted right colonic transposition (the so-called Deloyers procedure) are two possible solutions for creating a tension-free colorectal anastomosis after extended left colectomy. Few studies have reported their results of these two techniques and mostly via laparotomy. The aim of this study was to describe the trans-mesenteric colorectal anastomosis and the inverted right colonic transposition procedure via a laparoscopic approach and report the outcome in a series of 13 consecutive patients. Method This was retrospective chart review of laparoscopic colorectal surgery with trans-mesenteric colorectal anastomosis or the inverted right colonic transposition procedure from January 2015 up to 2019. An accompanying video demonstrates these two techniques. Results Thirteen consecutive patients underwent either a laparoscopic trans-mesenteric colorectal anastomosis (n = 9) or an inverted right colonic transposition procedure (n = 4). One patient had intra-operative presacral bleeding that was stopped successfully without conversion. Two patients had a postoperative intra-abdominal abscess, but no anastomotic complications were recorded. The median number of bowel movements per day after 6 months was 2 (range 2-5). Conclusions Trans-mesenteric colorectal anastomosis or the inverted right colonic transposition procedure is feasible laparoscopically. The now well-established classical advantages of the laparoscopic approach are associated with good functional outcome after these procedures.

Antidepressants are well-known drugs to treat depression and major depressive disorder for humans. However, the misuse and abuse of antidepressants keep increasing with several side effects reported. The aim of this study was to assess the potential adverse effects of 18 antidepressants by monitoring zebrafish larval locomotor activity performance based on the total distance traveled, burst movement count, and total rotation count at four dark-light intercalated phases. In general, zebrafish larvae displayed sedative effects after antidepressant exposure by showing a significant reduction in all of the locomotor activity-related endpoints. However, three antidepressants i.e., amitriptyline, amoxapine, and sertraline were able to trigger a significantly high locomotor activity in zebrafish larvae during the light cycle. These differences might be due to the pharmacologic differences among the antidepressants. In addition, since each antidepressant possesses a different dosage range from the other, overdoses of these antidepressants might also be the causes of these differences. Furthermore, based on these results, a further study was conducted to observe the effect of these three antidepressants in lower concentrations. From the results, biphasic effects in terms of zebrafish larval locomotor activity were demonstrated by these drugs. Even though further studies are still required to validate the mechanism, these findings indicate that these antidepressants might share a common mechanism responsible for their effects on zebrafish larval locomotor activity although there were some differences in potency of these effects.

Background:Interstitial lung diseases (ILD) could originate from idiopathic cause or secondary to connective tissue diseases (CTD). The most common causes of CTD associated ILD (CTD-ILD) include mixed connective tissue disease, systemic sclerosis (SSc), inflammatory myositis such as polymyositis (PM) and dermatomyositis (DM). Our preliminary data had demonstrated that ILD is not uncommon in patients with rheumatoid arthritis (RA) and Sjogren’s syndrome (SS) in Asia. Myositis-specific autoantibodies (MSAs) and myositis associate autoantibodies (MAAs) have been used for the early diagnosis of PM/DM and could be noticed in patients with idiopathic ILD. Our previous data also had identified that MSA/MAA were detected quite often in patients with CTD-ILD in addition to inflammatory myositis. Nonetheless, a specific group of ILD patients like interstitial pneumonia with autoimmune features (IPAF) are still challenging for pomologists, rheumatologist and radiologists, either in accurate diagnosis or treatment.Objectives:We aimed to identify the prevalence of serum MSA/MAAs and clinical diagnosis on imaging in patients with IPAF and CTD-ILD and define the correlation between MSA/MAA and clinical imaging features.Methods:Patients who had been suspected with autoimmune rheumatic diseases in the presence of interstitial lung diseases were included in this prospective study at a single medical center in Taiwan between February 2018 and November 2019. All enrolled patients had experienced clinical symptoms of ILD and been identified abnormalities on the chest plain films. All patients were inspected by both pulmonologists and rheumatologist. Computed tomography scans of chest had been reviewed by at least two pulmonary radiologists. Serological immunotherapy strips were performed to detect MSA/MAAs. Correlation analysis was performed among the different collected variables.Results:870 patients were reviewed by both pulmonologists and rheumatologists and received blood sampling including autoantibody profiling and MSA/MAA tests. The clinical diagnosis of CTD-ILD or IPAF were confirmed in 603 patients, who received 1078 chest CT scan due to clinically suspected CTD-ILD or IPAF. 33 patients received lung biopsies since other CTD-ILD or IPAF patients hesitate to receive invasive procedures. 78 patients had been admitted to intensive care units and received mechanical ventilation and were not suitable for lung biopsies. 22 of 33 patients received more than twice lung biopsies due to challenging diagnosis. 6 patients with CTD-ILD or IPAF had received extracorporeal membrane oxygenation (ECMO) due to ILD with secondary pulmonary infection and acute respiratory distress syndrome. The most commom detected MSA/MAA were anti-Ro-52 (27%), followed by anti-Ku (3.9%), and anti-Mi-2 (3.6%).SS is the most common rheumatic disease in patients with CTD-ILD. MSA/MAAs were identified in patients with IPAF (36.4 %) in the absence of specific rheumatic diseases. Anti-nuclear antibody (27.4%), rheumatoid factor immunoglobulin M (21.6%) and anti-Ro (13.7%) were the most common autoantibodies identified in patients with IPAF. Anti-Ro-52 was positively corelated with nonspecific interstitial pneumonia in patients with CTD-ILD or IPAF, Phi= 0.371 and 0.326, both p < 0.001, respectively.Conclusion:Early diagnosis of CTD-ILD and IPAF is still challenging for both pulmonologists, rheumatologists and radiologists. Identifying how serum MSA/MAAs contribute clinical manifestations on chest CT imaging is warranted and help clinical physicians and patients recognize the necessity of lung biopsy to reduce comorbidity.References:[1]Jee AS, et al. J Clin Med 2017[2]Wilfong EM, et al. Arthritis Rheumatol 2018[3]Sambataro G, et al. Eur Respir Rev 2018Disclosure of Interests:None declared

Electromigration and resistivity of Cu, Co and Ru on-chip interconnections have been investigated. Non-linered Co and Ru interconnects can have better interconnect resistance than Cu, if the Cu liner cannot be scaled down below 2 nm in future interconnect technologies. A similar resistivity size effect increase was observed in Cu, Co, and Ru. Multi-level Cu, Co or Ru back-end-of-line interconnects were fabricated using 7 and 10 nm node technology wafer processing steps. EM in 18 nm to 88 nm wide Co lines, 18–24 nm wide Cu with a thin Co cap and 18 to 24 nm wide Ru lines were tested. The electromigration activation energies for Cu with Co cap, Co and Ru were found to be 1.5–1.7 eV, 2.4–3.1 eV and 1.9 eV, respectively. These data showed that Cu with Co cap, Co and Ru interconnects all had highly reliable electromigration.

TP53 is one of the most commonly mutated genes in human cancer. Mutation or loss of TP53 can occur during the early stages of oncogenesis or as a later event as tumors progress to more aggressive forms. We used a patient-derived xenograft (PDX) model of triple negative breast cancer (TNBC) to investigate how p53 deficiency contributes to metastasis. The PDX line was generated by engrafting the primary breast tumor of a patient with TP53 wild-type metastatic TNBC into the humanized mammary fat pad of NOD/SCID mice. Isogenic lines differing only in TP53 status were generated from this model by silencing p53. Here we demonstrate that the p53-proficient and -deficient tumors metastasized from the mouse mammary gland and colonized the lung, liver, bone, brain, and lymph nodes with similar frequency. p53-deficient tumors grew faster in both the primary and metastatic sites as a result of increased mitosis and decreased apoptosis. Circulating tumor cells (CTCs) are currently being evaluated in p53-proficient and –deficient PDX models. Gene expression profiling identified candidate genes with potential clinical relevance that may be responsible for increased tumor growth upon p53 loss in late stage tumors. This model is also being used to identify genes that promote breast cancer metastasis. To enrich for metastasis, metastatic subpopulations of tumor cells were isolated from lungs and serially passaged in vivo. This serial passaging enriched for metastasis to multiple secondary sites. A transcriptional signature of putative metastasis genes was generated and is being functionalized with high throughput screening in vivo. Citation Format: Powell E, Shao J, Mistry N, Yuan Y, Tieu T, Decker K, Chen H-C, Cai S, Do K-A, Heffernan TP, Edwards J, Piwnica-Worms D, Piwnica-Worms H. p53 deficiency enhances metastatic potential of triple negative breast cancer by promoting growth in primary and metastatic sites. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-08.

Aims.Suicidal behaviour is prevalent among adolescents and is a significant predictor of future suicide attempts (SAs) and suicide death. Data on the prevalence and epidemiological characteristics of suicidal behaviour in Chinese adolescents are limited. This study was aimed to examine the prevalence, characteristics and risk factors of suicidal behaviour, including suicidal thought (ST), suicide plan (SP) and SA, in a large sample of Chinese adolescents.Method.This report represents the first wave data of an ongoing longitudinal study, Shandong Adolescent Behavior and Health Cohort. Participants included 11 831 adolescent students from three counties of Shandong, China. The mean age of participants was 15.0 (s.d. = 1.5) and 51% were boys. In November–December 2015, participants completed a structured adolescent health questionnaire, including ST, SP and SA, characteristics of most recent SA, demographics, substance use, hopelessness, impulsivity and internalising and externalising behavioural problems.Results.The lifetime and last-year prevalence rates were 17.6 and 10.7% for ST in males, 23.5 and 14.7% for ST in females, 8.9 and 2.9% for SP in males, 10.7 and 3.8% for SP in females, 3.4 and 1.3% for SA in males, and 4.6 and 1.8% for SA in females, respectively. The mean age of first SA was 12–13 years. Stabbing/cutting was the most common method to attempt suicide. Approximately 24% of male attempters and 16% of female attempters were medically treated. More than 70% of attempters had no preparatory action. Female gender, smoking, drinking, internalising and externalising problems, hopelessness, suicidal history of friends and acquaintances, poor family economic status and poor parental relationship were all significantly associated with increased risk of suicidal behaviour.Conclusions.Suicidal behaviour in Chinese adolescents is prevalent but less than that previously reported in Western peers. While females are more likely to attempt suicide, males are more likely to use lethal methods. Multiple child and family factors are associated with suicidal behaviour. These findings highlight the importance of early screening and intervention of suicidal behaviour in Chinese adolescents.

Fan-out processes are widely used in advanced packaging technologies to accommodate broader size variations and functional combinations of dies deployed on reconstituted wafers. However, such a process generates numerous mechanical loadings during the molding and curing phases. Without careful planning, failures such as “die shift” and “fly die” are frequently reported, which cause serious problems for subsequent processing. Among these issues, shear stress generation during molding, which is dominated by the resulted pressure distribution and increase in the viscosity of molding compound due to curing, has been recognized as a major controlling factor for defects of die shift and fly die. Prompted by the need to predict defects beforehand, this work presents an accurate 3D model for mold flow analysis by accounting for the curing kinetics. In conjunction with finite element structural analysis, the die shift induced by mold flow is estimated, and the results compare favorably with fabrication plant observations.

Background Based on ASAS axial spondyloarthritis (SpA) criteria, the presence of structural changes of sacroiliac (SI) joints such as sclerosis, bone erosion, joint space widening or ankyloses dose not meet the definition of active sacroiliitis on magnetic resonance imaging (MRI), if there is no bone marrow edema (BME). However only less than half Asian patients with SpA were characterized by BME. Neither serum inflammatory markers such as c reactive protein (CRP) nor erythrocyte sedimentation rate (ESR) is able to be useful as diagnostic markers in the early phase of SpA. HLA-B27 is associated with early diagnosis of SpA and axial inflammation of SI joints on MRI. Nonetheless, HLA-B27 is not associated with structural lesions of SI joints. All factors contribute to difficult defining early Asian SpA patients in the absence of serum HLA-B27 and active imaging inflammation. Objectives The aim of this study is to evaluate the prevalence of structure changes of SI joints on MRI in Taiwanese SpA patients in the absence of serum HLA-B27. Methods Thirty-three patients with inflammatory back pain and morning stiffness (disease duration more than 3 months) and high disease activity (BASDAI≥4) who had to be either serum HLA-B27 positive (10 patients) with ≥1 SpA-feature or HLA-B27 negative with ≥2 SpA-features (22 patients) were included in this prospective study. All patients did not meet the definition for a positive radiograph according to the modified New York criteria. MRI was performed with multiple sequence (Coronal and axial T1-weighted spin echo, coronal and axial short-tau inversion recovery). SI joints were evaluated for the prevalence of subchondral BME and structure changes (sclerosis, bone erosion, joint space widening and ankylosis). All patients were tested for X-rays of the pelvis and serum levels of ESR and CRP. Correlation analysis was performed among the different collected variables. Results Subchondral BME was only present in 8 of 23 patients with SpA in the absence of serum HLA-B27 (34.8%), while 7 of 10 (70%) HLA-B27 serum positive SpA patients had active BME on MRI. Structural changes of SI joints, including sclerosis, bone erosion and joint space widening were identified in 8 (80%), 10 (100%) and 5 (50%) SpA patients with positive serum HLA-B27, respectively. Nevertheless, these structural changes of SI joints on MRI were more common in HLA-B27 serum negative patients, as 15 (65.2%), 20 (87.0%) and 7 (30.4%) of 23 serum negative patients, respectively. Conclusions MRI contributes to detect structural changes of SI joints for patients with nonradiographic axial SpA in the absence of serum HLA-B27. References Rudwaleit, M. & Sieper, J. Nat. Rev. Rheumatol. 2012;8, 262–268. van Tubergen, A. & Weber, U. Nat. Rev. Rheumatol. 2012;8, 253–261. van der Heijde D, et al. Ann Rheum Dis 2017;0:1–14. Turina MC, et al. RMD Open 2017;2:e000319. Baraliakos, X. & Braun, J. Nat. Rev. Rheumatol. 2013;9, 498–502. Navallas M, et al. Radiographics. 2013;33:933–56. Lambert RGW, et al. Ann Rheum Dis 2016;75:1958–1963. Chung HY, et al. Ann Rheum Dis. 2011;70:1930–6. Disclosure of Interest None declared

BACKGROUND AND PURPOSE: CSF hypovolemia is a core feature of spontaneous intracranial hypotension. Spontaneous intracranial hypotension is characterized by orthostatic headache and radiologic manifestations, including CSF along the neural sleeves, diffuse pachymeningeal enhancement, and/or venous engorgement. However, these characteristics are only qualitative. Quantifying intraspinal CSF volumes could improve spontaneous intracranial hypotension diagnosis and evaluation of hypovolemic statuses in patients with spontaneous intracranial hypotension. The purpose of this study was to compare intraspinal CSF volumes across spontaneous intracranial hypotension stages and to test the clinical applicability of these measures. MATERIALS AND METHODS: A cohort of 23 patients with spontaneous intracranial hypotension and 32 healthy controls was subjected to brain MR imaging and MR myelography with 1.5T imaging. An automatic threshold-based segmentation method was used to calculate intraspinal CSF volumes at initial hospitalization (spontaneous intracranial hypotension-initial), partial improvement (spontaneous intracranial hypotension-intermediate), and complete recovery (spontaneous intracranial hypotension-recovery) stages. RESULTS: The mean intraspinal CSF volumes observed were the following: 95.31 mL for healthy controls, 72.31 mL for spontaneous intracranial hypotension-initial, 81.15 mL for spontaneous intracranial hypotension-intermediate, and 93.74 mL for spontaneous intracranial hypotension-recovery. Increased intraspinal CSF volumes were related to disease recovery (P < .001). The intraspinal CSF volumes of patients before complete recovery were significantly lower than those of healthy controls. With the estimated intradural CSF volumes as a reference, the intraspinal CSF volume percentage was lower in patients with spontaneous intracranial hypotension with venous engorgement than in those without it (P = .058). CONCLUSIONS: With a threshold-based segmentation method, we found that spinal CSF hypovolemia is fundamentally related to spontaneous intracranial hypotension. Intraspinal CSF volumes could be a sensitive parameter for the evaluation of treatment response and follow-up monitoring in patients with spontaneous intracranial hypotension.

Usher syndrome type III (USH3) characterized by progressive loss of vision and hearing is caused by mutations in the clarin-1 gene (CLRN1). Clrn1 knockout (KO) mice develop hair cell defects by postnatal day 2 (P2) and are deaf by P21-P25. Early onset profound hearing loss in KO mice and lack of information about the cochlear cell type that requires Clrn1 expression pose challenges to therapeutic investigation. We generated KO mice harboring a transgene, TgAC1, consisting of Clrn1-UTR (Clrn1 cDNA including its 5′ and 3′ UTR) under the control of regulatory elements (Atoh1 3′ enhancer/β-globin basal promoter) to direct expression of Clrn1 in hair cells during development and down regulate it postnatally. The KO-TgAC1 mice displayed delayed onset progressive hearing loss associated with deterioration of the hair bundle structure, leading to the hypothesis that hair cell expression of Clrn1 is essential for postnatal preservation of hair cell structure and hearing. Consistent with that hypothesis, perinatal transfection of hair cells in KO-TgAC1 mice with a single injection of AAV-Clrn1-UTR vector showed correlative preservation of the hair bundle structure and hearing through adult life. Further, the efficacy of AAV-Clrn1 vector was significantly attenuated, revealing the potential importance of UTR in gene therapy.

Background Previous studies have demonstrated that biological aging has a negative influence on the therapeutic effects of mesenchymal stem cells (MSCs)-based therapy. Using a rat myocardial infarction (MI) model, we tested the hypothesis that silent mating type information regulation 2 homolog 1 (SIRT1) may ameliorate the phenotype and improve the function of aged MSCs and thus enhance the efficacy of aged MSCs-based therapy. Methods Sixty female rats underwent left anterior descending coronary artery ligation and were randomly assigned to receiving: intramyocardial injection of cell culture medium (DMEM group); SIRT1 overexpression vector-treated aged MSCs (SIRT1-aged MSCs group) obtained from aged male SD rats or empty vector-treated aged MSCs (vector-aged MSCs group). Another 20 sham-operated rats that underwent open-chest surgery without coronary ligation or any other intervention served as controls. Results SIRT1-aged MSC group exhibited enhanced blood vessel density in the border zone of MI hearts, which was associated with reduced cardiac remodeling, leading to improved cardiac performance. Consistent with the in vivo data, our in vitro experiments also demonstrated that SIRT1 overexpression ameliorated aged MSCs senescent phenotype and recapitulated the pro-angiogenesis property of MSCs and conferred the anti-stress response capabilities, as indicated by increases in pro-angiogenic factors, angiopoietin 1 (Ang1) and basic fibroblast growth factor (bFGF), expressions and a decrease in anti-angiogenic factor thrombospondin-1 (TBS1) at mRNA levels, and increases in Bcl-2/Bax ratio at protein level. Conclusions Up-regulating SIRT1 expression could enhance the efficacy of aged MSCs-based therapy for MI as it relates to the amelioration of senescent phenotype and hence improved biological function of aged MSCs.

Experimental, controlled, animal study. To assess the effects of vitamins C and E (VCE) treatment on oxidative stress and programmed cell deaths after rat spinal cord injury (SCI), as well as functional recovery. Taiwan. Fifty-four Sprague–Dawley rats were used for the experimental procedure. In the sham group, laminectomy at T10 was performed, followed by impactor contusion of the spinal cord. In the control group, only a laminectomy was performed without contusion. Oxidative stress status was assessed by measuring the spinal cord tissue content of superoxide dismutase (SOD) and gluthatione peroxidase (GSH-Px) activities. We also evaluated the effects of combined VCE treatment using western blot to analyze expression of cleaved caspase-3 and microtubule-associated protein light chain 3 (LC3), and the Basso, Beattie and Bresnahan (BBB) scale to evaluate functional outcomes. Combined treatment of VCE significantly counteracted the effects of spinal cord contusion on oxidative stress represented by activities of SOD and GSH-Px (P

BackgroundHistorically, long-term survival rates in locally advanced non-small-cell lung cancer (NSCLC) have been disappointingly low, and treatment toxicities have been significant.AimsTo assess survival outcomes, treatment toxicities, patterns of disease recurrence and prognostic variables for patients with locally advanced NSCLC treated with concurrent chemoradiation.MethodsPatients who completed treatment with chemotherapy and simultaneous chest irradiation for locally advanced NSCLC at the Royal Prince Alfred Hospital (Sydney, Australia) in the period January 1994 to July 2009 were identified. We retrospectively reviewed the patients' medical records to obtain patient demographic data, clinical data, information on tumour characteristics and treatment administered, and outcome data such as survival, treatment toxicities and tumour recurrence patterns.ResultsOur patient cohort consisted largely of urban-dwelling male smokers with good baseline performance status. As of December 2012, 93/105 patients had died. Median overall and progression-free survival was 20 months and 11 months respectively. The 5-year survival rate was 17%. Eight patients had survived longer than 8 years, and 13 patients enjoyed progression-free survival longer than 3 years. Locoregional tumour recurrence occurred most frequently, followed by brain and bone metastases. Adverse effects from chemoradiation included varying degrees of gastrointestinal, pulmonary and haematological toxicity. Three deaths occurred from radiation-induced pneumonitis. Weight loss at presentation was statistically significantly associated with worse overall survival in univariate analyses (P = 0.01).ConclusionsOur survival results are consistent with the recent international literature and indicate that a proportion of patients with locally advanced NSCLC can enjoy prolonged survival following treatment with concurrent chemoradiation.

Summary Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR-16, miR-221 and let-7i were over-expressed in AS T cells and the expression of miR-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR-16, miR-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti-CD3+anti-CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti-CD3+anti-CD28+ lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti-CD3+anti-CD28+ LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-γ) immune response in T cells.

Background Medication non-adherence is common among renal dialysis patients. High degrees of non-adherence in randomized controlled trials (RCTs) can lead to failure to detect a true treatment effect. Cardio-protective pharmacological interventions have shown no consistent benefit in RCTs involving dialysis patients. Whether non-adherence contributes to this lack of efficacy is unknown. We aimed to investigate how medication adherence and drug discontinuation were assessed, reported and addressed in RCTs, evaluating cardiovascular or mortality outcomes in dialysis patients. Methods Electronic database searches were performed in MEDLINE, EMBASE & Cochrane CENTRAL for RCTs published between 2005–2015, evaluating self-administered medications, in adult dialysis patients, which reported clinical cardiovascular or mortality endpoints, as primary or secondary outcomes. Study characteristics, outcomes, methods of measuring and reporting adherence, and data on study drug discontinuation were analyzed. Results Of the 642 RCTs in dialysis patients, 22 trials (12 placebo controlled), which included 19,322 patients, were eligible. The trialed pharmacological interventions included anti-hypertensives, phosphate binders, lipid-lowering therapy, cardio-vascular medications, homocysteine lowering therapy, fish oil and calcimimetics. Medication adherence was reported in five trials with a mean of 81% (range: 65–92%) in the intervention arm and 84.5% (range: 82–87%) in the control arm. All the trials that reported adherence yielded negative study outcomes for the intervention. Study-drug discontinuation was reported in 21 trials (mean 33.2%; 95% CI, 22.0 to 44.5, in intervention and 28.8%; 95% CI, 16.8 to 40.8, in control). Trials with more than 20% study drug discontinuation, more often yielded negative study outcomes (p = 0.018). Non-adherence was included as a contributor to drug discontinuation in some studies, but the causes of discontinuation were not reported consistently between studies, and non-adherence was listed under different categories, thereby potentiating the misclassification of adherence. Conclusions Reporting of medication adherence and study-drug discontinuation in RCTs investigating cardiovascular or mortality endpoints in dialysis patients are inconsistent, making it difficult to compare studies and evaluate their impact on outcomes. Recommendations for consistent reporting of non-adherence and causes of drug discontinuation in RCTs will therefore help to assess their impact on clinical outcomes. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0449-1) contains supplementary material, which is available to authorized users.

Partial discharge (PD) may cause insulation deteriorations in power facilities and may demonstrate impact on the reliability. Therefore PD detection with pattern recognition is seen as an effective approach in the high-voltage (HV) insulation diagnostics of power systems. Based on an extension method, a PD recognition system for HV power cables is proposed in this study. A PD detector is used to measure raw three-dimension PD patterns of cross-linked polyethylene (XLPE) power cables using an L sensor, according to which two fractal features (the fractal dimension and the lacunarity) and the mean discharge are extracted as critical PD features that form the cluster domains of defect types. The matter-element models of the PD defect types are then built according to the PD features derived from practical experimental results. The PD defect type can be directly identified by the correlation degrees between a tested pattern and the matter-element models. The recognition ability is investigated on 160 sets of PD patterns of XLPE power cables and compared with a multilayer neural network and K-means method. The results show that a high accuracy together with a high tolerance in the presence of noise interference is reached by use of the extension method.

This research takes the resistance formula of spherical cavity expansion theory as its foundation. It establishes a predictive model of the residual velocity, ballistic limit velocity, and penetration depth of ogival nose projectiles striking metal target plates at high speed. They are aimed at 6061-T651 aluminum plates of different thicknesses using the iterative algorithm of the numerical method, thereby investigating the theoretical calculation of the residual velocity, penetration depth, ballistic limit velocity, and changes in resistance of ogival nose projectiles when making a normal impact target. In addition to analyzing the resistance undergone by the projectile nose section, this predictive model also considers the effects of friction resistance of the projectile shank section. In this research, we also used the finite element software LS-DYNA to perform a simulated analysis on the penetration depth of the aluminum plate after normal perforation by ogival nose projectiles. Ballistic test experiments were then performed using 0.30” AP (armor piercing) bullets. Finally, a comparative analysis was performed based on the theoretical model, experiments, and numerical simulation results.

In this paper, white light-emitting diodes (LEDs) with air-gap embedded package were proposed and fabricated by a simple method including pulsed spray coating. The lumen efficiency of air-gap embedded LED was enhanced by 8.8% at driving current of 350 mA, compared to conventional remote phosphor white LED. This improvement was due to the enhanced utilization of blue and yellow rays, which were confirmed by pulse current-dependent correlated color temperature (CCT). The utilization efficiency of blue rays was enhanced by 12.4% due to the embedded air-gap layer. The simulation results performed by Monte-Carlo ray tracing method agreed with our experiments, which showed enhancement in lumen efficiency and similar CCT. Finally, the electric field intensity versus different thickness for air-gap and no air-gap embedded white LED was calculated to check the incident blue rays trapped in phosphor layer.

SHIEH S.-H., CHEN H.-C., TSAI W.-C., KUO S.-Y., TSAI Y.-F. & LU C.-H. (2012) Impact of breast cancer patients' awareness on attendance at screening. International Nursing Review59, 353–361 Aim: The purpose of this study is to investigate the impact of breast cancer awareness on the attendance for screening among women with breast cancer prior to diagnoses of breast cancer. Background: Breast cancer is the most commonly diagnosed cancer for women in Taiwan and its incidence rate continues to increase. However, screening for breast cancer is still not common even if the incidence rate has topped the list from 2003 to 2010. Methods: A cross-sectional study was conducted among women diagnosed with breast cancer. Subjects (535 women) were recruited from two medical centres in central Taiwan. Information on attendance for breast cancer screening was collected by self-report. Chi-square test and logistic regression were utilized to analyse the relationships between awareness of breast cancer and attendance at screening. Findings: The results indicated that pre-diagnostic awareness of ‘the concept of early treatment relating to higher cure rate’[odds ratio (OR): 4.09; 95% confidence interval (CI): 1.12–14.9], ‘various breast cancer screening methods’ (OR:3.00; 95% CI: 1.23–7.30), ‘the coverage of breast cancer screening programme in the National Health Insurance’ (OR:1.76; 95% CI: 1.03–3.02) and ‘breast self-examination after each menstrual cycle’ (OR:3.42; 95% CI: 1.99–5.87) were all significantly associated with the screening procedures performed. Conclusions: Findings of this study indicated that particular attention should be paid towards enhancement of women's knowledge for prevention and early detection of breast cancer through educational efforts by nurse professionals, medical institutions and/or civil organizations.

Electron microscopy investigation has been carried for an n- ZnO /p- GaN:Mg heterojunction ultraviolet (UV) light-emitting diode device, where the n- ZnO layer was grown by atomic layer deposition on the p-type GaN:Mg /undoped GaN structure prepared on c- Al 2 O 3 substrate. Threading dislocations, formed at the interface of the GaN/Al2O3 , disappeared at the interface of n- ZnO /p- GaN during post-deposited rapid thermal annealing and accordingly the n- ZnO layer became an almost perfect single crystal including only a few surviving dislocations. An interfacial layer was found along the (0001) interface between the n- ZnO and p- GaN:Mg layers. Scanning transmission microscopy analysis revealed that the interfacial layer was composed of ZnO crystal, which connected coherently with the neighboring n- ZnO and p- GaN:Mg . This interfacial layer contained a few atomic percents of Mg , the atoms of which had been diffused from the p- GaN:Mg . The high quality crystalline n- ZnO and the interfacial layer forming a ZnO/GaN interface states are responsible for the UV electroluminescence from the ZnO .

High-quality epitaxial AlN films were deposited on sapphire substrates at low growth temperature using a helicon sputtering system. SAW filters fabricated on the AlN films exhibited excellent characteristics, with center frequency of 354.2 MHz, which corresponds to a phase velocity of 5667 m/s. An oscillator fabricated using AlN-based SAW devices is presented and applied to deep-UV light detection. A frequency downshift of about 43 KHz was observed when the surface of SAW device was illuminated by a UV source with dominant wavelength of around 200 nm. The results indicate the feasibility of developing remote sensors for deep-UV measurement using AlN-based SAW oscillators.

Commercial fashion designers are usually focused on developing designs using color, fabric and style lines, whereas artistic fashion designers whose primary goal is innovation are keen on developing designs by means of a peculiar manner of presentation or a new conception of fabric. The aims of this research are to analyze the potential for developing novel methods of generating material and create new fabrics that are useful for both fashion and decorative art, as well as explore the potential uses with the newly generated fabrics. Acknowledging that fabric is a crucial element for fashion, this researcher set about investigating the potential use of sewing thread for creating fabric. This study documents a personal experimentation with a new dimension whereby fabric can be generated from overstitched threads using a variety of techniques; non-woven, patterned non-woven, interweaving, knitting, and embroidering. This study demonstrates not only the possibility of approaching artistic fashion by manipulating overstitching, but also the feasibility of conducting a fashion design process in which product aesthetics is generated from yarn texture, fabric structure, and garment construction. Thus, this study contributes to developing an approach in which overstitching and fashion are merged to integrate a new dimension of creation.

Gender-specific determinants of blood pressure (BP) values and control have not been the focus of clinical hypertension research. The purpose of this analysis was to identify gender-specific and multi-level (physician and patient) determinants of BP values and predictors of uncontrolled BP. We completed a subgroup analysis comparing men and women who participated in the Belgian PREVIEW study of second-line treatment effectiveness of valsartan, applying two-level hierarchical modelling of 90-day BP values and guideline-defined BP control. In total, 1665 women and 1525 men were treated by 504 general practitioners. Fewer women than men reached systolic BP (SBP) (P=0.015) and combined BP targets at 90 days (P=0.007). More than 26% of the variance in 90-day SBP (intra-class correlation coefficient (ICC)=0.270) and diastolic BP (DBP) (ICC=0.262) was attributable to physician-level factors for men; the physician-level ICCs for SBP and DBP were 0.259 and 0.268, respectively, for women. Determinants of 90-day BP values and predictors of uncontrolled BP varied considerably by gender. Many of the multi-level determinants of BP by gender are amenable to intervention, and the remainder can serve as warning signs to clinicians that patients may remain vulnerable to poor outcomes associated with sub-optimal BP control.

Through the laser-ablation and aerosol-jet printing techniques, a novel photoluminescent quantum-dots device with microscale patterns has been demonstrated as a white-light emitting source with stable emission at different driving currents and larger color productivity domain.

Colloidal quantum dots which can emit red, green, and blue colors are incorporated with a micro-LED array to demonstrate a feasible choice for future display technology. The pitch of the micro-LED array is 40 μm, which is sufficient for high-resolution screen applications. The method that was used to spray the quantum dots in such tight space is called Aerosol Jet technology which uses atomizer and gas flow control to obtain uniform and controlled narrow spots. The ultra-violet LEDs are used in the array to excite the red, green and blue quantum dots on the top surface. To increase the utilization of the UV photons, a layer of distributed Bragg reflector was laid down on the device to reflect most of the leaked UV photons back to the quantum dot layers. With this mechanism, the enhanced luminous flux is 194% (blue), 173% (green) and 183% (red) more than that of the samples without the reflector. The luminous efficacy of radiation (LER) was measured under various currents and a value of 165 lm/Watt was recorded.

In this study, a novel photoluminescent quantum dots device with laser-processed microscale patterns has been demonstrated to be used as a white light emitting source. The pulsed laser ablation technique was employed to directly fabricate microscale square holes with nano-ripple structures onto the sapphire substrate of a flip-chip blue light-emitting diode, confining sprayed quantum dots into well-defined areas and eliminating the coffee ring effect. The electroluminescence characterizations showed that the white light emission from the developed photoluminescent quantum-dot light-emitting diode exhibits stable emission at different driving currents. With a flexibility of controlling the quantum dots proportions in the patterned square holes, our developed white-light emitting source not only can be employed in the display applications with color triangle enlarged by 47% compared with the NTSC standard, but also provide the great potential in future lighting industry with the correlated color temperature continuously changed in a wide range.

A self-healing mmWave SoC integrating an 8052 microcontroller with 12kB of memory, an ADC, a temperature sensor, and a 3-stage cascode 60GHz LNA, implemented in a 32nm SOI CMOS technology exhibits a peak gain of 21dB, an average 3.3dB NF from 53 to 62GHz and 18mW power consumption. An indirect NF sensing algorithm was implemented on the integrated uC, which enables an adaptive biasing algorithm to reduce the 60GHz NF sigma and LNA power consumption by 37 and 40%, respectively, across P,V,T.

High stresses generated from chip-package interactions (CPI), especially when large die is flip mounted on organic substrate using Pb-free C4 bumps, can easily cause low-k delamination. A novel scheme by applying an elastic material can effectively reduce the transmitted stresses and, thus, resolve the interfacial delamination issue. Along with an optimized chip-package integration solution, a reliable interconnect structure with good electrical performance, has been successfully demonstrated.