Computational imaging enables retrieval of the spatial information of an object with the use of single-pixel detectors. By projecting a series of known random patterns and measuring the backscattered ...intensity, it is possible to reconstruct a two-dimensional (2D) image. We used several single-pixel detectors in different locations to capture the 3D form of an object. From each detector we derived a 2D image that appeared to be illuminated from a different direction, even though only a single digital projector was used for illumination. From the shading of the images, the surface gradients could be derived and the 3D object reconstructed. We compare our result to that obtained from a stereophotogrammetric system using multiple cameras. Our simplified approach to 3D imaging can readily be extended to nonvisible wavebands.
A power transformer will yield a frequency response which is unique to its mechanical geometry and electrical properties. Changes in the frequency response of a transformer can be potential ...indicators of winding deformation as well as other structural and electrical problems. A diagnostic tool which leverages this knowledge in order to detect such changes is frequency-response analysis (FRA). To date, FRA has been used to identify changes in a transformer's frequency response but with limited insight into the underlying cause of the change. However, there is now a growing research interest in specifically identifying the structural change in a transformer directly from its FRA signature. The aim of this paper is to support FRA interpretation through the development of wideband three-phase transformer models which are based on three types of FRA tests. The resulting models can be used as a flexible test bed for parameter sensitivity analysis, leading to greater insight into the effects that geometric change can have on transformer FRA. This paper will demonstrate the applicability of this modeling approach by simultaneously fitting each model to the corresponding FRA data sets without a priori knowledge of the transformer's internal dimensions, and then quantitatively assessing the accuracy of key model parameters.
A debate exists within the medical community on whether the linear no-threshold model of ionizing radiation exposure accurately predicts the subsequent incidence of radiogenic cancer. In this ...article, we evaluate evidence refuting the linear no-threshold model and corollary efforts to reduce radiation exposure from CT and nuclear medicine imaging in accord with the as-low-as-reasonably-achievable principle, particularly for children. Further, we review studies demonstrating that children are not, in fact, more radiosensitive than adults in the radiologic imaging dose range, rendering dose reduction for children unjustifiable and counterproductive. Efforts to minimize nonexistent risks are futile and a major source of persistent radiophobia. Radiophobia is detrimental to patients and parents, induces stress, and leads to suboptimal image quality and avoidance of imaging, thus increasing misdiagnoses and consequent harm while offering no compensating benefits.
Immune-related adverse events (irAEs) typically occur within 4 months of starting anti-programmed cell death protein 1 (PD-1)-based therapy anti-PD-1 ± anti-cytotoxic T-lymphocyte-associated protein ...4 (CTLA4), but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAEs in patients receiving anti-PD-1-based immunotherapy.
Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD-1-based therapy and surviving >1 year. Onset, clinical features, management and outcomes of irAEs were examined.
One hundred and eighteen patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4), with an estimated incidence of 5.3% (95% confidence interval 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53 months). Eighty-seven patients (74%) were on anti-PD-1 at irAE onset, 15 patients (12%) were <3 months from the last dose and 16 patients (14%) were >3 months from the last dose of anti-PD-1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥grade 3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD-1 and a multiple-organ irAE with onset 11 months after ceasing anti-PD-1. Early irAEs (<12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%).
Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAEs, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD-1. The risk of delayed irAE should be considered when deciding the duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.
•The incidence of delayed irAEs >12 months after commencing anti-PD-1 was 5.3%.•Delayed irAEs occurred in 118 patients; these were often high grade (39% G3+) including two delayed irAE-related deaths.•Delayed irAEs were often difficult to manage; 68% required steroids and 23% required an additional immunosuppressive agent.•Most occurred during anti-PD-1 therapy (74%), but delayed irAEs were also reported up to 26 months after stopping anti-PD-1.
The genetic background of Atopic Dermatitis (AD) with chronic pruritus is complex. Filaggrin (FLG) is an essential gene in the epidermal barrier formation s. Loss-of-function (LOF) variants in FLG ...associated with skin barrier dysfunction constitute the most well-known genetic risk factor for AD. In this study, we focused on the frequency and effect of FLG loss-of-function variants in association with self-reported age-of-onset of AD. The dataset consisted of 386 whole-genome sequencing (WGS) samples. We observe a significant association between FLG LOF status and age-of-onset, with earlier age of onset of AD observed in the FLG LOF carrier group (p-value 0.0003, Wilcoxon two-sample test). We first tested this on the two most prevalent FLG variants. Interestingly, the effect is even stronger when considering all detected FLG LOF variants. Having two or more FLG LOF variants associates with the onset of AD at 2 years of age. In this study, we have shown enrichment of rare variants in the EDC region in cases compared with controls. Age-of-onset analysis shows not only the effect of the FLG and likely EDC variants in terms of the heightened risk of AD, but foremost enables to predict early-onset, lending further credence to the penetrance and causative effect of the identified variants. Understanding the genetic background and risk of early-onset is suggestive of skin barrier dysfunction etiology of AD with chronic pruritus.
Maximum safe surgical resection followed by adjuvant chemoradiation and temozolomide chemotherapy is the current standard of care in the management of newly diagnosed high grade glioma. However, ...there are controversies about the optimal number of adjuvant temozolomide cycles. This study aimed to compare the survival benefits of 12 cycles against 6 cycles of adjuvant temozolomide adults with newly diagnosed high grade gliomas.
Adult patients with newly diagnosed high grade gliomas, and a Karnofsky performance status>60%, were randomized to receive either 6 cycles or 12 cycles of adjuvant temozolomide. Patients were followed-up for assessment of overall survival (OS) and progression-free survival (PFS) by brain MRI every 3 months within the first year after treatment and then every six months.
A total of 100 patients (6 cycles, 50; 12 cycles, 50) were entered. The rate of treatment completion in 6 cycles and 12 cycles groups were 91.3% and 55.1%, respectively. With a median follow-up of 26 months, the 12-, 24-, 36-, and 48-month OS rates in 6 cycles and 12 cycles groups were 81.3% vs 78.8%, 58.3% vs 49.8%, 47.6% vs 34.1%, and 47.6% vs 31.5%, respectively (p-value=.19). Median OS of 6 cycles and 12 cycles groups were 35 months (95% confidence interval (CI), 11.0 to 58.9) and 23 months (95%CI, 16.9 to 29.0). The 12-, 24-, 36-, and 48- month PFS rates in 6 cycles and 12 cycles groups were 70.8% vs 56.9%, 39.5% and 32.7%, 27.1% vs 28.8%, and 21.1% vs 28.8%, respectively (p=.88). The Median PFS of 6 cycles and 12 cycles groups was 18 months (95% CI, 14.8 to 21.1) and 16 (95% CI, 11.0 to 20.9) months.
Patients with newly diagnosed high grade gliomas treated with adjuvant temozolomide after maximum safe surgical resection and adjuvant chemoradiation do not benefit from extended adjuvant temozolomide beyond 6 cycles.
Prospectively registered with the Iranian Registry of Clinical Trials: IRCT20160706028815N3. Date registered: 18/03/14.
Data on the efficacy and safety of COVID-19 vaccines in patients with malignancy are immature. In this paper, we assessed the literature involving the use of COVID-19 vaccines in cancer patients and ...reported the seroconversion rates as the main outcome and severity of COVID-19 infection and side effects following COVID-19 vaccination as the secondary outcomes.
A systematic review with meta-analysis was performed. Searches were conducted in electronic websites, databases, and journals, including Scopus, PubMed, Embase, and Web of Science from January 01, 2019, to November 30, 2021. Studies reporting data on the safety and efficacy of COVID vaccine in cancer patients using any human samples were included. The risk of bias was assessed using the NEWCASTLE-OTTAWA scale in the included studies.
A total of 724 articles were identified from databases, out of which 201 articles were duplicates and were discarded. Subsequently, 454 articles were excluded through initial screening of the titles and abstracts. Moreover, 41 studies did not report the precise seroconversion rate either based on the type of cancer or after injection of a second dose of COVID vaccine. Finally, 28 articles met all the inclusion criteria and were included in this systematic review. The overall seroconversion rates after receiving a second dose of COVID-19 vaccine, based on type of cancer were 88% (95% CI, 81%-92%) and 70% (95% CI, 60%-79%) in patients with solid tumors and hematologic malignancies, respectively.
Overall, we conclude that vaccination against COVID-19 in patients with active malignancies using activated and inactivated vaccines is a safe and tolerable procedure that is also accompanied by a high efficacy.
The chimeric fusion oncogene early B-cell factor 1-platelet-derived growth factor receptor-β (EBF1-PDGFRB) is a recurrent lesion observed in Philadelphia-like B-acute lymphoblastic leukemia (B-ALL) ...and is associated with particularly poor prognosis. While it is understood that this fusion activates tyrosine kinase signaling, the mechanisms of transformation and importance of perturbation of EBF1 activity remain unknown. EBF1 is a nuclear transcription factor required for normal B-lineage specification, commitment and development. Conversely, PDGFRB is a receptor tyrosine kinase that is normally repressed in lymphocytes, yet PDGFRB remains a common fusion partner in leukemias. Here, we demonstrate that the EBF1-PDGFRB fusion results in loss of EBF1 function, multimerization and autophosphorylation of the fusion protein, activation of signal transducer and activator of transcription 5 (STAT5) signaling and gain of interleukin-7 (IL-7)-independent cell proliferation. Deregulation and loss of EBF1 function is critically dependent on the nuclear export activity of the transmembrane (TM) domain of PDGFRB. Deletion of the TM domain partially rescues EBF1 function and restores IL-7 dependence, without requiring kinase inhibition. Moreover, we demonstrate that EBF1-PDGFRB synergizes with loss of IKAROS function in a fully penetrant B-ALL in vivo. Thus, we establish that EBF1-PDGFRB is sufficient to drive leukemogenesis through TM-dependent loss of transcription factor function, increased proliferation and synergy with additional genetic insults including loss of IKAROS function.
Neoadjuvant chemotherapy (NC) can improve the resectability of hepatic colorectal metastases (CRM). However, there is concern regarding its impact on operative risk. We reviewed 750 consecutive liver ...resections performed for CRM in a single unit (1996-2005) to evaluate whether NC affected morbidity and mortality. Redo hepatic resections or patients receiving adjuvant chemotherapy following primary resection were excluded. A total of 245 resections were performed in patients not requiring NC (control group) (mean age 63, 67% male) and 252 in patients who had NC (mean age 62, 67% male). The mean (s.d.) duration of surgery was less in the control group (241(64) vs 255(64)min, P=0.014) as was the mean blood loss (390(264) vs 449(424)ml, P=0.069). Postoperative mortality (2 vs 2%) and morbidity (27 vs 29%, P=0.34) was similar between groups. More NC patients developed septic (2.4%) or respiratory (10.3%) complications compared to controls (0 and 5.3%, P<0.03), with significantly more surgical complications if the interval between stopping NC and undergoing surgery was <or=4 weeks (11%), compared to 5-8 (5.5%) or 9-12 (2.6%) weeks (P=0.009). The data suggest that liver resection for CRM is safe following NC. Early hepatobiliary involvement in multidisciplinary cancer care may lead to avoidance of potential perioperative adverse events.
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