Tracking with a mixed continuous-discrete Conditional Random Field

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Immunotherapy for Malignant Gliomas: A Roadmap for the Future

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Neuroinflammation in Alzheimer's disease wanes with age

<p>Abstract</p> <p>Background</p> <p>Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated.</p> <p>Methods</p> <p>In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years). The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1), HLA class II (CR3/43) and glial fibrillary acidic protein (GFAP).</p> <p>Results</p> <p>By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD.</p> <p>Conclusion</p> <p>Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.</p

Natural Illumination from Multiple Materials Using Deep Learning

Recovering natural illumination from a single Low-Dynamic Range (LDR) image is a challenging task. To remedy this situation we exploit two properties often found in everyday images. First, images rarely show a single material, but rather multiple ones that all reflect the same illumination. However, the appearance of each material is observed only for some surface orientations, not all. Second, parts of the illumination are often directly observed in the background, without being affected by reflection. Typically, this directly observed part of the illumination is even smaller. We propose a deep Convolutional Neural Network (CNN) that combines prior knowledge about the statistics of illumination and reflectance with an input that makes explicit use of these two observations. Our approach maps multiple partial LDR material observations represented as reflectance maps and a background image to a spherical High-Dynamic Range (HDR) illumination map. For training and testing we propose a new data set comprising of synthetic and real images with multiple materials observed under the same illumination. Qualitative and quantitative evidence shows how both multi-material and using a background are essential to improve illumination estimations

Biochemical and biological characterization of wild-type and ATPase-deficient Cockayne syndrome B repair protein

Cockayne syndrome (CS) is a nucleotide excision repair disorder characterized by sun (UV) sensitivity and severe developmental problems. Two genes have been shown to be involved: CSA and CSB. Both proteins play an essential role in preferential repair of transcription-blocking lesions from active genes. In this study we report the purification and characterization of baculovirus-produced HA-His6-tagged CSB protein (dtCSB), using a highly efficient three-step purification protocol. Microinjection of dtCSB protein in CS-B fibroblasts shows that it is biologically functional in vivo. dtCSB exhibits DNA-dependent ATPase activity, stimulated by naked as well as nucleosomal DNA. Using structurally defined DNA oligonucleotides, we show that double-stranded DNA and double-stranded DNA with partial single-stranded character but not true single-stranded DNA act as efficient cofactors for CSB ATPase activity. Using a variety of substrates, no overt DNA unwinding by dtCSB could be detected, as found with other SNF2/SWI2 family proteins. By site-directed mutagenesis the invariant lysine residue in the NTP-binding motif of CSB was substituted with a physicochemically related arginine. As expected, this mutation abolished ATPase activity. Surprisingly, the mutant protein was nevertheless able to partially rescue the defect in recovery of RNA synthesis after UV upon microinjection in CS-B fibroblasts. These results indicate that integrity of the conserved nucleotide-binding domain is important for the in vivo function of CSB but that also other properties independent from ATP hydrolysis may contribute to CSB biological functions

Rates of Low-Value Service in Australian Public Hospitals and the Association With Patient Insurance Status.

Importance: Low-value services have limited or no benefit to patients. Rates of low-value service in public hospitals may vary by patient insurance status, given that there may be different financial incentives for treatment of privately insured patients. Objective: To assess the variation in rates of 5 low-value services performed in Australian public hospitals according to patient funding status (ie, private or public). Design, Setting, and Participants: This retrospective cross-sectional study analyzed New South Wales public hospital data from January 2013 to June 2018. Patients included in the sample were over age 18 years and eligible to receive low-value services based on diagnoses and concomitant procedures. Data analysis was conducted from June to December 2020. Main Outcomes and Measures: Hospital-specific rates of low-value knee arthroscopic debridement, vertebroplasty for osteoporotic spinal fractures, hyperbaric oxygen therapy, oophorectomy with hysterectomy, and laparoscopic uterine nerve ablation for chronic pelvic pain were measured. For each measure, rates within each public hospital were compared by patient funding status descriptively and using multilevel models. Results: A total of 219 862 inpatients were included in analysis from 58 public hospitals across the 5 measures. A total of 38 365 (22 904 [59.7%] women; 12 448 [32.4%] aged 71-80 years) were eligible for knee arthroscopic debridement for osteoarthritis; 2520 (1924 [76.3%] women; 662 [26.3%] aged 71-80 years), vertebroplasty for osteoporotic spinal fractures; 162 285 (82 046 [50.6%] women; 28 255 [17.4%] aged 61-70 years), hyperbaric oxygen therapy; 15 916 (7126 [44.8%] aged 41-50 years), oophorectomy with hysterectomy; and 776 (327 [42.1%] aged 18-30 years), uterine nerve ablation for chronic pelvic pain. Overall rates of low-value services varied considerably between measures, with the lowest rate for hyperbaric oxygen therapy (0.3 procedures per 1000 inpatients [47 of 158 220 eligible inpatients]) and the highest for vertebroplasty (30.8 procedures per 1000 eligible patients [77 of 2501 eligible inpatients]). There was significant variation in rates between hospitals, with a few outlying hospitals (ie, <10), particularly for knee arthroscopy (range from 1.8 to 21.0 per 1000 eligible patients) and vertebroplasty (range from 13.1 to 70.4 per 1000 eligible patients), with higher numerical rates of low-value services among patients with private insurance than for those without. However, there was no association overall between patient insurance status and low-value services. Overall differences in rates among those with and without private insurance by individual procedure type were not statistically significant. Conclusions and Relevance: There was significant variation in rates of low-value services in public hospitals. While there was no overall association between private insurance and rate of low-value services, private insurance may be associated with low-value service rates in some hospitals. Further exploration of factors specific to local hospitals and practices are needed to reduce this unnecessary care