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The global COVID-19 pandemic has challenged nurse leaders in ways that one could not imagine six months ago. Along with ongoing priorities of providing high quality, cost-effective and safe care, nurse leaders are also committed to creating environments that support excellence in patient and family experience. This article will provide exemplars of how nurse leaders used decisive decision-making, adapted to novel situations and issues, ensured reliable and safe delivery of care and engaged patients, families and their workforce to create excellent experiences of care during the pandemic. Throughout this crisis, nurse leaders have learned how to grapple with quick and often uncertain decision-making, adapted ways to engage patient and family amidst new care situations and operational policies, delivered care reliably with ever changing metrics and measures and created environments to support and bring smiles to nurses and other health care staff. New opportunities to care for and positively engage patients and families have emerged. Experience Framework This article is associated with the Culture & Leadership lens of The Beryl Institute Experience Framework. (http://bit.ly/ExperienceFramework) Access other PXJ articles related to this lens. Access other resources related to this lens

Objective We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus. Materials and methods Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry. Serum levels of anti-dsDNA, anti-histone and anti-chromatin antibodies were measured by ELISA. Frequencies of B cells, activated and regulatory CD4+ T cells as well as Th1, Th2, Th17 cells were measured by flow cytometry. RT-qPCR was used to measure expression levels of interferon-signature and T-cell subset related as well as miR155-associated genes. Results After induction of lupus, miR155-deficient mice had significant less pulmonary involvement (perivascular inflammatory area in mm2/mm2 lung area 0.00092±0.00015 vs. 0.0027±0.00075, p = 0.0347) and renal disease (glomerular activity score 1.95±0.19 vs 3±0.26, p = 0.0029) compared to wild types. MiR155-deficient mice had significantly lower serum levels of disease-associated auto-antibodies and decreased frequencies of activated CD4+CD25+ (Foxp3-) cells. Upon restimulation, CD4+ cells showed a less pronounced Th2 and Th17 and a slightly decreased Th1 response in mir155-deficient mice. Pristane-treated wild types showed significantly up-regulated expression of genes related to the INF-signature (MX1, IP10, IRF7, ISG15). Conclusions MiR155-deficient mice had less severe organ involvement, lower serum auto-antibody levels, a less prominent T cell response and lower expressions of genes jointly responsible for disease development. Thus, antagonizing miR155 might be a future approach in treating SLE.

Since sodium stibogluconate (SSG) inhibited phosphatases including SHP-1 and augmented anti-tumor actions of IFN-α2b in vitro and in mice, two Phase I trials of SSG/IFN-α2b combination were undertaken to evaluate safety and target inhibition. Escalating doses of SSG (200-1200 mg/m2) and fixed doses of IFN-α2b (3x106 units/m2) with or without chemotherapy (dacarbazine, vinblastine, cisplatin) were evaluated for side effects and impact on SHP-1 phospho-substrates and IFNα-stimulated-genes (ISGs) in peripheral blood in 40 patients with metastatic melanoma, soft tissue sarcomas, gastrointestinal stromal tumors, and breast or colorectal carcinomas who did not have other established treatment options. Common adverse events were bone marrow suppression, fatigue, gastrointestinal upset, and asymptomatic lipase elevation (n=13); the latter was dose related and mostly after 10d of SSG/IFN-α2b in combination. Levels of SHP-1 substrates (pSTAT1, pSTAT3, pLck and pSlp76) were increased (up to 3x) in peripheral blood cells following SSG with no potentiation by combination with IFN-α2b. Representative ISGs in peripheral blood were induced after IFN-α2b at 4 and 24 hrs with selective modulations by combination. The median time on trials was 2.3 months (10-281d) with no objective regression of disease. Alive at 1y were 17/40 (43%) patients and after 2y were 8/40 (20%) following treatment initiation. These data demonstrate that SSG impacted signal molecules consistent with PTP inhibition and was tolerated in combination with IFN-α2b. Phase II investigations of SSG could safely utilize doses of up to 1200 mg/m2 of SSG for up to 10d alone or in combination with IFN-α2b with or without chemotherapy.

The range of empirically based evidence on interventions for meeting the needs of students with social, emotional and behavioural difficulties (SEBD) in mainstream schools is rich and varied. This paper is based on an international literature search and review of studies that were published between 1980 and 2012. Particular attention is given to evidence that define the qualities and skills of effective teachers and the value of behavioural and cognitive behavioural interventions.

The immunobiology of tumor-infiltrating dendritic cells (DCs) can be strongly influenced by the cytokine environment present in the malignant tissue. We have previously identified discrete melanoma lines, inducing E-cadherin expression on monocyte-derived DCs in vitro. We demonstrate here that this effect, independent of cell contact, is not inducible in the presence of tumor lysates and requires the constitutive expression of IFN stimulated gene 15 (ISG15) by malignant cells. High-density oligonucleotide arrays were used to investigate the expression pattern of 7000 genes in RNA from two melanoma cell clones competent for E-cadherin induction and two clones devoid of DC-modulating capacity. A total of 13 genes encoding soluble proteins were expressed at higher magnitude in melanomas able to induce E-cadherin expression on DCs. Combining those data with quantitative protein assays, we could narrow our investigation down to three factors: the chemokine CCL5 and the cytokines ISG15 and type I IFNs. Strikingly,7 ng/ml of ISG15 could be detected in the corresponding melanoma-conditioned medium and induction of E-cadherin on DCs failed in the presence of antibodies neutralizing ISG15 protein. Most importantly, strong cytoplasmic expression of ISG15 was detected by immunohistochemistry in the original tumor specimen from which the melanoma cell lines under investigation were derived. These data describe a novel property of ISG15 targeting induction of E-cadherin on DCs and possibly influencing their migratory behavior.

A linear regression for a short and long sequence of hydrologic events is used to lengthen the short sequence. The lengthened sequence consists of the original observations and regressed values plus noise, where the noise is a random variable with zero mean and variance proportional to the variance of the observations for the short sequence about the line of regression. Estimates of the mean and variance for the lengthened sequence are shown to be unbiased. If the correlation coefficient, which measures the strength of the linear regression, exceeds about 0.5, then the estimates of the mean and variance based on the lengthened sequence are better estimators of the population values of the mean and variance than the estimates based on the observations for the short sequence. If noise is not added to the regressed values, the correlation coefficient must exceed about 0.8 to obtain improvement in the estimates by use of correlated values. INTRODUCTION In statistical studies of hydrology, the assumption is made that a sequence of a finite number of observed events represents a random sample from an infinite population of such events, where the outcome of each event is governed by some probability distribution. Any change hi the hydrologic regime with which a given sequence is associated is reflected in a change of the probability distribution. Although various parameters may be used to describe a probability distribution, the mean, variance, and skewness are three parameters which provide information about the most useful properties of any probability distribution. The mean is a measure of central tendency, a value about which the events tend to cluster, whereas the variance measures the dispersion or average spread of the events about the mean. The skewness is a measure of the asymmetry of the distribution of the events about the mean. These three parameters cannot define a probability distribution uniquely, except in special cases; nevertheless, they do provide characteristics which may be used to describe and compare various hydrologic phenomena. The population values of these parameters are generally unknown, but the values may be estimated from a sequence of observations. How reliable these estimates are depends primarily upon the period or length of the sequence the total number of observations. If the estimates are unbiased, their reliability increases with an increase of the sequence length. To increase a sequence length by making additional observations in time in order to obtain more reliable estimates of the mean, variance, and skewness is not always operationaUy or economically feasible. If not, recourse must be had to other procedures for increasing a sequence length. One such procedure, which is the topic of discussion in this paper, is to utilize the relations among hydrologic phenomena. A relation among the concurrent observations for a short and a long sequence can be used to obtain estimates of the nonobserved events for the short sequence which correspond to the observed events for the nonconcurrent portion of the long sequence. In this manner the short sequence is lengthened. The observed and estimated events for the lengthened sequence can be used to obtain estimates of the mean, variance, and skewness. Whether or not the reliability of these estimates is greater than that for the estimates of these parameters based only on the observations depends mainly upon the strength of the relation between the concurrent observations for the short and long sequences. A mathematical evaluation of this procedure has been made by several investigators under the assumptions that (1) the events are independently distributed in time, (2) the concurrent events for two sequences have a joint normal distribution, (3) the relation between the concurrent events is defined by a linear regression, and (4) no changes occur hi the hydrologic regimes with which the sequences are associated. The strength of the linear regression is measured by the productmoment correlation coefficient. Under the assumption of normality, only the mean and variance need to be considered because these two parameters uniquely define a normal probability distribution. For this distribution, the skewness is zero. El E2 STATISTICAL STUDIES IN HYDROLOGY H. A. Thomas, Jr. (written commun. 1956), showed that the lengthened sequence yields an unbiased estimate of the mean, and if the product-moment correlation coefficient exceeds lf-yNi 2 where NI is the length of the concurrent period, the reliability of this estimate of the mean is greater than that based only on the observations for the short sequence. These results also were obtained by W. G. Cochran (1953) in an earlier and independent study of a double sampling problem. J. R. Rosenblatt (1959) showed that the lengthened sequence yields a biased estimate of the variance, and that the reliability of this estimate is greater than that based only on the observations for the short sequence if the product-moment correlation coefficient exceeds about 0.8. M. B. Fiering (1963) obtained somewhat similar results for the estimates of the mean and variance when more than one long sequence is related to a short sequence by a multiple linear regression. In the studies cited above, the estimated events in the lengthened sequence were regression estimates, that is, estimates which correspond to values on the line of regression. These estimates tend to yield a smaller variance than would the real observations. In order to "preserve" the variance inherent with the observations, a random component must be added to the regression estimates. This component, often referred to as noise, is normally distributed with zero mean and variance proportional to the variance of the observations for the short sequence about the line of regression. This paper reports the results of an investigation made to determine the reliability of estimates of the mean and variance computed from a lengthened sequence when noise is added to the regression values. Noise is shown to have no effect on the reliability of the estimate of the mean. However, the addition of noise is shown to lead to an unbiased estimate of the variance for the lengthened sequence. The reliability of this estimate is greater than that when no noise is added to the regression values. STATISTICAL MODEL The long and short sequences for a pair of hydrologic phenomena are denoted by x and y. In general, the two phenomena need not be the same. If, for example, y denotes streamflow, x may denote streamflow, precipitation, temperature, or a geochronologic phenomena such as tree-ring widths. The observed events for the long and short sequences are represented as where NI is the length of the short sequence and (Ni-+-Na) is the length of the long sequence. For this representation of the two sequences, NI also denotes the concurrent period of observation. In practice, the NI observations for the short sequence need not correspond to the first NI observations of the long sequence, nor need the NI concurrent observations of x and y occur consecutively. However, there is no loss of generality if the two sequences are represented as above. The concurrent observations x and y are assumed to have a joint normal probability distribution with parameters nx, ny, a2., a2,, and p=ft