The Performance of the Robo-AO Laser Guide Star Adaptive Optics System at the Kitt Peak 2.1-m Telescope

Robo-AO is an autonomous laser guide star adaptive optics system recently commissioned at the Kitt Peak 2.1-m telescope. Now operating every clear night, Robo-AO at the 2.1-m telescope is the first dedicated adaptive optics observatory. This paper presents the imaging performance of the adaptive optics system in its first eighteen months of operations. For a median seeing value of $1.31^{\prime\prime}$, the average Strehl ratio is 4\% in the $i^\prime$ band and 29\% in the J band. After post-processing, the contrast ratio under sub-arcsecond seeing for a $2\leq i^{\prime} \leq 16$ primary star is five and seven magnitudes at radial offsets of $0.5^{\prime\prime}$ and $1.0^{\prime\prime}$, respectively. The data processing and archiving pipelines run automatically at the end of each night. The first stage of the processing pipeline shifts and adds the data using techniques alternately optimized for stars with high and low SNRs. The second "high contrast" stage of the pipeline is eponymously well suited to finding faint stellar companions.Comment: 12 pages, 16 figures, to be submitted to PAS

Long- term outcome of paediatric patients with ANCA vasculitis

Background: Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment-related morbidity and mortality is important. The aim of this study is to describe the long-term clinical course of paediatric patients with ANCA vasculitis.Methods: The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis.Results: We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only. Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy.Conclusion: Close long-term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease-related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis

Ospemifene Displays Broad-Spectrum Synergistic Interactions with Itraconazole Through Potent Interference with Fungal Efflux Activities

Azole antifungals are vital therapeutic options for treating invasive mycotic infections. However, the emergence of azole-resistant isolates combined with limited therapeutic options presents a growing challenge in medical mycology. To address this issue, we utilized microdilution checkerboard assays to evaluate nine stilbene compounds for their ability to interact synergistically with azole drugs, particularly against azole-resistant fungal isolates. Ospemifene displayed the most potent azole chemosensitizing activity, and its combination with itraconazole displayed broad-spectrum synergistic interactions against Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus (ΣFICI = 0.05–0.50). Additionally, in a Caenorhabditis elegans infection model, the ospemifene-itraconazole combination significantly reduced fungal CFU burdens in infected nematodes by ~75–96%. Nile Red efflux assays and RT-qPCR analysis suggest ospemifene interferes directly with fungal efflux systems, thus permitting entry of azole drugs into fungal cells. This study identifies ospemifene as a novel antifungal adjuvant that augments the antifungal activity of itraconazole against a broad range of fungal pathogens

Repurposing Approach IdentifiesPitavastatin as a Potent AzoleChemosensitizing Agent EffectiveAgainst Azole-Resistant CandidaSpecies

The limited number of antifungals and the rising frequency of azole-resistant Candida species are growing challenges to human medicine. Drug repurposing signifies an appealing approach to enhance the activity of current antifungal drugs. Here, we evaluated the ability of Pharmakon 1600 drug library to sensitize an azole-resistant Candida albicans to the effect of fluconazole. The primary screen revealed 44 non-antifungal hits were able to act synergistically with fluconazole against the test strain. Of note, 21 compounds, showed aptness for systemic administration and limited toxic effects, were considered as potential fluconazole adjuvants and thus were termed as “repositionable hits”. A follow-up analysis revealed pitavastatin displaying the most potent fluconazole chemosensitizing activity against the test strain (ΣFICI 0.05) and thus was further evaluated against 18 isolates of C. albicans (n = 9), C. glabrata (n = 4), and C. auris (n = 5). Pitavastatin displayed broad-spectrum synergistic interactions with both fluconazole and voriconazole against ~89% of the tested strains (ΣFICI 0.05–0.5). Additionally, the pitavastatin-fluconazole combination significantly reduced the biofilm-forming abilities of the tested Candida species by up to 73%, and successfully reduced the fungal burdens in a Caenorhabditis elegans infection model by up to 96%. This study presents pitavastatin as a potent azole chemosensitizing agent that warrant further investigation

Assessment of health-related quality of life in patients receiving stem cell therapy for end-stage liver disease: an Egyptian study

INTRODUCTION: This prospective cohort study aimed to assess the influence of stem cell therapy (SCT) on health-related quality of life (HRQOL) by using the SF-36 v2 and to elucidate the influence of objective clinical variables on subjective HRQOL. METHODS: The study included 100 chronic liver disease patients (50 received SCT, and 50 received supportive medical treatment (SMT)). Both groups completed a modified SF-36 v2 form before therapy and at 1-, 3-, 6-, and 12-month intervals. Fifty healthy Egyptian volunteers were enrolled in the study and completed the SF-36 v2 form once. RESULTS: Both SCT and SMT groups showed significantly lower pretherapy SF 36 v2 scores compared with healthy volunteers. In SCT-treated patients, limited complications were encountered (SF-36 v2 scores showed significant improvement in all domains throughout the follow-up period) compared with the deterioration shown by SMT patients after therapy. A significant association was detected between SF-36 v2 scores and laboratory data in SCT patients during the first month after therapy. The grade of ascites improved during the follow-up in SCT compared with SMT patients. The mean survival time was 277.56 days (95% CI, 246.217 to 308.903) for SMT and 359.300 days (95% CI, 353.022 to 365.578) for SCT patients (log rank, 0.00). Stem cell-treated patients showed no malignancies. CONCLUSIONS: SCT positively affects health-related quality of life in cirrhosis patients. The survival rate was significantly improved after SCT

Underdetermined DOA Estimation Using MVDR-Weighted LASSO

The direction of arrival (DOA) estimation problem is formulated in a compressive sensing (CS) framework, and an extended array aperture is presented to increase the number of degrees of freedom of the array. The ordinary least square adaptable least absolute shrinkage and selection operator (OLS A-LASSO) is applied for the first time for DOA estimation. Furthermore, a new LASSO algorithm, the minimum variance distortionless response (MVDR) A-LASSO, which solves the DOA problem in the CS framework, is presented. The proposed algorithm does not depend on the singular value decomposition nor on the orthogonality of the signal and the noise subspaces. Hence, the DOA estimation can be done without a priori knowledge of the number of sources. The proposed algorithm can estimate up to ((M2−2)/2+M−1)/2 sources using M sensors without any constraints or assumptions about the nature of the signal sources. Furthermore, the proposed algorithm exhibits performance that is superior compared to that of the classical DOA estimation methods, especially for low signal to noise ratios (SNR), spatially-closed sources and coherent scenarios

Collective magnetism at multiferroic vortex domain walls

Topological defects have been playgrounds for many emergent phenomena in complex matter such as superfluids, liquid crystals, and early universe. Recently, vortex-like topological defects with six interlocked structural antiphase and ferroelectric domains merging into a vortex core were revealed in multiferroic hexagonal manganites. Numerous vortices are found to form an intriguing self-organized network. Thus, it is imperative to find out the magnetic nature of these vortices. Using cryogenic magnetic force microscopy, we discovered unprecedented alternating net moments at domain walls around vortices that can correlate over the entire vortex network in hexagonal ErMnO3 The collective nature of domain wall magnetism originates from the uncompensated Er3+ moments and the correlated organization of the vortex network. Furthermore, our proposed model indicates a fascinating phenomenon of field-controllable spin chirality. Our results demonstrate a new route to achieving magnetoelectric coupling at domain walls in single-phase multiferroics, which may be harnessed for nanoscale multifunctional devices.Comment: 18 pages, 10 figure

Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer

Background: Regulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC) the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC). Methods and Findings: Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival. Conclusions: Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression