ANALYSIS OF NUCLEI FLUORESCENCE HISTOGRAMS USING NON-LINEAR FUNCTIONS OR WAVELETS

Histograms based on 5,000 nuclei from cells (Chinese hamster ovary cells, bone marrow cells) are used to determine the coefficient of variation (CV) of observations surrounding the highest peak. The cells are subjected to various treatments, for example exposure to herbicides. By eyeballing the histogram, an interval under the highest peak is determined. The CV calculated from the histogram on the eyeballed interval is the response variable in an ANOVA. To avoid the subjectivity of eyeballing the histogram, non-linear functions such as the Gaussian density function can be used to model the histogram. The CV may then be determined from the parameter estimates. In many experiments nonlinear functions modeling the histograms smooth away differences in CV s obtained this way, though visually the histograms appear to be different. Then nonlinear functions or wavelets can be used to obtain intervals for calculating CV s of the histograms restricted to these intervals. The nonlinear models require close initial values for each histogram, while the wavelets just require choice of wavelet and level of decomposition

Effective antibiotic conservation by emergency antimicrobial stewardship during a drug shortage

We present the first description of an antimicrobial stewardship program (ASP) used to successfully manage a multi-antimicrobial drug shortage. Without resorting to formulary restriction, meropenem utilization decreased by 69% and piperacillin-tazobactam by 73%. During the shortage period, hospital mortality decreased (P=.03), while hospital length of stay remained unchanged.Infect Control Hosp Epidemiol 2017;38:356–359</jats:p

Vaccine message framing and parents' intent to immunize their infants for MMR

BACKGROUND AND OBJECTIVE: Emphasizing societal benefits of vaccines has been linked to increased vaccination intentions in adults. It is unclear if this pattern holds for parents deciding whether to vaccinate their children. The objective was to determine whether emphasizing the benefits of measles-mumps-rubella (MMR) vaccination directly to the vaccine recipient or to society differentially impacts parents' vaccine intentions for their infants. METHODS: In a national online survey, parents (N = 802) of infants <12 months old were randomly assigned to receive 1 of 4 MMR vaccine messages: (1) the Centers for Disease Control and Prevention Vaccine Information Statement (VIS), (2) VIS and information emphasizing the MMR vaccine's benefits to the child, (3) VIS and information emphasizing societal benefits, or (4) VIS and information emphasizing benefits both to the child and society. Parents reported their likelihood of vaccinating their infants for MMR on a response scale of 0 (extremely unlikely) to 100 (extremely likely). RESULTS: Compared with the VIS-only group (mean intention = 86.3), parents reported increased vaccine intentions for their infants when receiving additional information emphasizing the MMR vaccine's benefits either directly to the child (mean intention = 91.6, P = .01) or to both the child and society (mean intention = 90.8, P = .03). Emphasizing the MMR vaccine's benefits only to society did not increase intentions (mean intention = 86.4, P = .97). CONCLUSIONS: We did not see increases in parents' MMR vaccine intentions for their infants when societal benefits were emphasized without mention of benefits directly to the child. This finding suggests that providers should emphasize benefits directly to the child. Mentioning societal benefits seems to neither add value to, nor interfere with, information highlighting benefits directly to the child

The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies

BACKGROUND Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies. METHODS Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified. RESULTS In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3(rd) versus 1(st) tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3(rd) versus 1(st) tertile greater than 3.2, were significantly (p≤.002) associated with disease progression among hospitalized patients only. CONCLUSIONS In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome

HLA Class I and Genetic Susceptibility to Type 1 Diabetes: Results From the Type 1 Diabetes Genetics Consortium

OBJECTIVE-We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS-Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients. RESULTS-Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes-associated alleles were B*5701 (odds ratio 0.19; P = 4 x 10(-11)) and B*3906 (10.31; P = 4 X 10(-10)). Other significantly type 1 diabetes-associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class H. Other class I type 1 diabetes associations appear to be specific to individual class H haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403). CONCLUSIONS-These data indicate that HLA class I alleles, in addition to and independently from HLA class H alleles, are associated with type 1 diabetes. Diabetes 59:2972-2979, 201

Mutational analyses of UPIIIA, SHH, EFNB2, and HNF1β in persistent cloaca and associated kidney malformations

OBJECTIVES: ‘Persistent cloaca’ is a severe malformation affecting females in which the urinary, genital and alimentary tracts share a single conduit. Previously, a Uroplakin IIIA (UPIIIA) mutation was reported in one individual with persistent cloaca, and UPIIIA, Sonic Hedgehog (SHH), Ephrin B2 (EFNB2) and Hepatocyte Nuclear Factor 1β (HNF1β) are expressed during the normal development of organs that are affected in this condition. HNF1β mutations have been associated with uterine malformations in humans, and mutations of genes homologous to human SHH or EFNB2 cause persistent cloaca in mice. PATIENTS AND METHODS: We sought mutations of coding regions of UPIIIA, SHH, EFNB2 and HNF1β genes by direct sequencing in a group of 20 patients with persistent cloaca. Most had associated malformations of the upper renal tract and over half had impaired renal excretory function. The majority of patients had congenital anomalies outside the renal/genital tracts and two had the VACTERL association. RESULTS: Apart from a previously described index case, we failed to find UPIIIA mutations, and no patient had a SHH, EFNB2 or HNF1β mutation. CONCLUSION: Persistent cloaca is only rarely associated with UPIIIA mutation. Despite the fact that SHH and EFNB2 are appealing candidate genes, based on their expression patterns and mutant mice phenotypes, they were not mutated in these humans with persistent cloaca. Although HNF1β mutations can perturb paramesonephric duct fusion in humans, HNF1β was not mutated in persistent cloaca

Upregulation of the Oct3/4 network in basal breast cancer is associated with its metastatic potential and shows tissue dependent variability

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of th

Shall We (Math and) Dance?

Can we use mathematics, and in particular the abstract branch of category theory, to describe some basics of dance, and to highlight structural similarities between music and dance? We first summarize recent studies between mathematics and dance, and between music and categories. Then, we extend this formalism and diagrammatic thinking style to dance.Comment: preprin

DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy

Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. In contrast to wild-type controls, Dusp5 null mice infused with ANG II developed PH and right ventricular (RV) hypertrophy. PH in Dusp5 null mice was associated with thickening of the medial layer of small PAs, suggesting an in vivo role for DUSP5 as a negative regulator of ANG II-dependent SMC proliferation. Consistent with this, overexpression of DUSP5 blocked ANG II-mediated proliferation of cultured human pulmonary artery SMCs (hPASMCs) derived from patients with idiopathic PH or from failed donor controls. Collectively, the data support a role for DUSP5 as a feedback inhibitor of ANG II-mediated ERK signaling and PASMC proliferation and suggest that disruption of this circuit leads to adverse cardiopulmonary remodeling. NEW & NOTEWORTHY Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism