Instability of reconstruction of the low CMB multipoles

We discuss the problem of the bias of the Internal Linear Combination (ILC) CMB map and show that it is closely related to the coefficient of cross-correlation K(l) of the true CMB and the foreground for each multipole l. We present analysis of the cross-correlation for the WMAP ILC quadrupole and octupole from the first (ILC(I)) and the third (ILC(III)) year data releases and show that these correlations are about -0.52-0.6. Analysing 10^4 Monte Carlo simulations of the random Gaussian CMB signals, we show that the distribution function for the corresponding coefficient of the cross-correlation has a polynomial shape P(K,l)\propto(1-K^2)^(l-1). We show that the most probable value of the cross-correlation coefficient of the ILC and foreground quadrupole has two extrema at K ~= +/-0.58$. Thus, the ILC(III) quadrupole represents the most probable value of the coefficient K. We analyze the problem of debiasing of the ILC CMB and pointed out that reconstruction of the bias seems to be very problematic due to statistical uncertainties. In addition, instability of the debiasing illuminates itself for the quadrupole and octupole components through the flip-effect, when the even (l+m) modes can be reconstructed with significant error. This error manifests itself as opposite, in respect to the true sign of even low multipole modes, and leads to significant changes of the coefficient of cross-correlation with the foreground. We show that the CMB realizations, whose the sign of quadrupole (2,0) component is negative (and the same, as for all the foregrounds), the corresponding probability to get the positive sign after implementation of the ILC method is about 40%.Comment: 11 pages, 5 figure

Raman scattering in C_{60} and C_{48}N_{12} aza-fullerene: First-principles study

We carry out large scale {\sl ab initio} calculations of Raman scattering activities and Raman-active frequencies (RAFs) in ${\rm C}_{48}{\rm N}_{12}$ aza-fullerene. The results are compared with those of ${\rm C}_{60}$. Twenty-nine non-degenerate polarized and 29 doubly-degenerate unpolarized RAFs are predicted for ${\rm C}_{48}{\rm N}_{12}$. The RAF of the strongest Raman signal in the low- and high-frequency regions and the lowest and highest RAFs for ${\rm C}_{48}{\rm N}_{12}$ are almost the same as those of ${\rm C}_{60}$. The study of ${\rm C}_{60}$ reveals the importance of electron correlations and the choice of basis sets in the {\sl ab initio} calculations. Our best calculated results for ${\rm C}_{60}$ with the B3LYP hybrid density functional theory are in excellent agreement with experiment and demonstrate the desirable efficiency and accuracy of this theory for obtaining quantitative information on the vibrational properties of these molecules.Comment: submitted to Phys.Rev.

Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases

Background and Aim: Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble, high molecular weight proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the extracellular matrix from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. Methods: The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. Results: The resulting list of differentially expressed proteins significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the extracellular matrix component. One of the proteins upregulated in liver metastatic ECM, Annexin A1, was not previously studied in the context of cancer-associated matrisome. Here we show that Annexin A1 was markedly upregulated in colon cancer cell lines compared to cancer cells of other origin, and also overrepresented in human primary colorectal lesions as well as hepatic metastases in comparison with their adjacent healthy tissue counterparts. Conclusions: In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes Annexin A1 as a putative target for this disease

Cell-Cycle Dependence of Transcription Dominates Noise in Gene Expression

The large variability in mRNA and protein levels found from both static and dynamic measurements in single cells has been largely attributed to random periods of transcription, often occurring in bursts. The cell cycle has a pronounced global role in affecting transcriptional and translational output, but how this influences transcriptional statistics from noisy promoters is unknown and generally ignored by current stochastic models. Here we show that variable transcription from the synthetic tetO promoter in S. cerevisiae is dominated by its dependence on the cell cycle. Real-time measurements of fluorescent protein at high expression levels indicate tetO promoters increase transcription rate ~2-fold in S/G2/M similar to constitutive genes. At low expression levels, where tetO promoters are thought to generate infrequent bursts of transcription, we observe random pulses of expression restricted to S/G2/M, which are correlated between homologous promoters present in the same cell. The analysis of static, single-cell mRNA measurements at different points along the cell cycle corroborates these findings. Our results demonstrate that highly variable mRNA distributions in yeast are not solely the result of randomly switching between periods of active and inactive gene expression, but instead largely driven by differences in transcriptional activity between G1 and S/G2/M.GM095733BBBE 103316MIT Startup Fun

Cancer vaccine trial evaluations: immunobridging and potential immunological endpoints

Therapeutic cancer vaccines are an emerging class of immunotherapy, but challenges remain in effectively adapting approved vaccines to a growing number of adjuvants, combination therapies, and antigen-selection methods. Phase III clinical trials remain the gold standard in determining clinical benefit, but are slow and resource intensive, whilst radiological surrogates often fail to reliably predict clinical benefit. Using immunological surrogates of efficacy, deployed in ‘immunobridging trials’, could present a viable alternative, safely speeding up cancer vaccine development in a cost-effective manner. Whilst this approach has proven successful in infectious disease vaccines, identifying reliable immunological correlates of protection has proven difficult for cancer vaccines. Most clinical trials, which present the richest source of data to establish a correlate, rely on peripheral blood samples and standard immunoassays that are ill-equipped to capture the complexity of the vaccine-induced anti-tumour response. This review is the first to outline the importance and challenges of establishing immunological surrogates for cancer vaccines in the context of immunobridging trials, evaluating current immunoassay methods, and highlighting the need for techniques that can characterize tumour-infiltrating lymphocytes and the suppressive tumour microenvironment across a range of patients. The authors propose adapting trial designs for surrogate discovery, including combining phase I/II trials and the use of multi-omics approaches. Successful immunological surrogate development could enable future immunobridging trials to accelerate the optimization of approved cancer vaccines without requiring new phase III trials, promoting faster clinical implementation of scientific advances and patient benefits

From the rhetoric to the real: a critical review of how the concepts of recovery and social inclusion may inform mental health nurse advanced level curricula – the eMenthe project

Objectives This critical review addresses the question of how the concepts of recovery and social inclusion may inform mental health nurse education curricula at Master’s level in order to bring about significant and positive change to practice. Design This is a literature-based critical review incorporating a modified rapid review method. It has been said that if done well, this approach can be highly relevant to health care studies and social interventions, and has substantial claims to be as rigorous and enlightening as other, more conventional approaches to literature (Rolfe, 2008). Data sources In this review, we have accessed contemporary literature directly related to the concepts of recovery and social inclusion in mental health. Review methods We have firstly surveyed the international literature directly related to the concepts of recovery and social inclusion in mental health and used the concept of emotional intelligence to help consider educational outcomes in terms of the required knowledge, skills and attitudes needed to promote these values-based approaches in practice. Results A number of themes have been identified that lend themselves to educational application. International frameworks exist that provide some basis for the developments of recovery and social inclusion approaches in mental health practice, however the review identifies specific areas for future development. Conclusions This is the first article that attempts to scope the knowledge, attitudes and skills required to deliver education for Master’s level mental health nurses based upon the principles of recovery and social inclusion. Emotional intelligence theory may help to identify desired outcomes especially in terms of attitudinal development to promote the philosophy of recovery and social inclusive approaches in advanced practice. Whilst recovery is becoming enshrined in policy, there is a need in higher education to ensure that mental health nurse leaders are able to discern the difference between the rhetoric and the reality

Mental health among healthcare workers and other vulnerable groups during the COVID-19 pandemic and other coronavirus outbreaks: A rapid systematic review.

INTRODUCTION: Although most countries and healthcare systems worldwide have been affected by the COVID-19 pandemic, some groups of the population may be more vulnerable to detrimental effects of the pandemic on mental health than others. The aim of this systematic review was to synthesise evidence currently available from systematic reviews on the impact of COVID-19 and other coronavirus outbreaks on mental health for groups of the population thought to be at increased risk of detrimental mental health impacts. MATERIALS AND METHODS: We conducted a systematic review of reviews on adults and children residing in a country affected by a coronavirus outbreak and belonging to a group considered to be at risk of experiencing mental health inequalities. Data were collected on symptoms or diagnoses of any mental health condition, quality of life, suicide or attempted suicide. The protocol for this systematic review was registered in the online PROSPERO database prior to commencing the review (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=194264). RESULTS: We included 25 systematic reviews. Most reviews included primary studies of hospital workers from multiple countries. Reviews reported variable estimates for the burden of symptoms of mental health problems among acute healthcare workers, COVID-19 patients with physical comorbidities, and children and adolescents. No evaluations of interventions were identified. Risk- and protective factors, mostly for healthcare workers, showed the importance of personal factors, the work environment, and social networks for mental health. CONCLUSIONS: This review of reviews based on primary studies conducted in the early months of the COVID-19 pandemic shows a lack of evidence on mental health interventions and mental health impacts on vulnerable groups in the population