Irresponsible contagions: Propagating harmful behavior through imitation

‘Monkey see, monkey do’ is an old saying referring to imitating another\u27s actions without necessarily understanding the underlying motivations or being concerned about consequences, such as propagating harmful behaviors. This study examines the likelihood of firms imitating and proliferating others’ unethical, irresponsible practices thereby exacerbating harmful effects among even more firms; in doing so, irresponsible contagions can rapidly spread more broadly, negatively affecting even more consumers. Building upon rivalry- and information-based imitation theories, we examine if harmful behaviors of others, in combination with misbehavior of referent firms, influences the likelihood of a firm to engage in irresponsible consumer-related practices. After examining 25,824 firm-year observations over 12 years, our findings suggest that imitation of harmful product-related behavior occurs; with size an important factor related to proliferation of harmful behaviors. Testing the model against a holdout sample finds 94% accuracy. Implications for scholars, managers, and policy makers are explored

Using Macro Archival Databases to Expand Theory in Micro Research

Databases containing macro-level data are an underutilized methodological tool for expanding theory in micro research (i.e., individual and team) to the macro (i.e., organizational and higher) level of analysis. We describe how macro archival databases support different theoretical approaches for upwardly expanding micro research and summarize unanswered research questions across micro domains requiring upward expansion. We describe 31 macro archival databases as a resource for testing research questions that upwardly expand theorizing in micro domains and how databases enable methodological best practices (i.e., data collection over time, multiple measures of a construct, multilevel statistical controls, missing data and outlier management) that are often difficult to apply in typical micro research. Finally, we demonstrate the feasibility and benefits of using macro archival databases through an empirical illustration in the workplace diversity domain: positive effects of manager gender diversity and manager industry gender diversity on firm performance (i.e., ROA and ROE)

Analysis of Five Field Event Performances at the Drake Relays by Age and Gender, 1978-2008

Advisor: David S. SenchinaWe analyzed gender and age differences in Drake Relays performance distances for 2 jumping (long jump and triplejump) and 3 throwing (discus, javelin, shotput) field events for 31 years (1978-2008). The top 10 performances were taken each year for 4 groups: high school (HS) boys, HS girls, college/university (C/U) men, C/U women. Our data set included 4403 performances total, because not all ages/genders competed in all events or for the same number of years. Generally, females significantly improved their jumping or throwing distances whereas males showed no improvements or significantly declined in performance. HS girls showed statistically significant improvements in all 3 of their events (discus, shotput, long jump), and C/U women showed improvements in 4 of their 5 events (discus, javelin, shotput, triplejump) and demonstrated no change in long jump performance. In comparison, HS boys showed no changes in 2 of their 3 events (discus and shotput) and significantly shorter distance in long jump, and C/U men demonstrated significantly shorter throwing or jumping distances in 4 of their 5 events (javelin, shotput, long jump, triplejump) and no change in discus. Despite the improvements in female performance distances, males threw or jumped further than females in all events for all years except for discus, where C/U women were out-throwing HS boys by 2008. As the Drake Relays includes athletes from across the country, these differences likely reflect national trends and are possibly explained by forces such as increased pressure for youth sport specialization, declining popularity of track-and-field, and Title IX.Drake University, College of Arts and Sciences, Department of Biology, Biochemistry, Cell and Molecular Biology ; College of Pharmacy and Health Science

Perinatal risk factors associated with acute kidney injury severity and duration among infants born extremely preterm

Background We evaluated time-varying perinatal risk factors associated with early (≤7 post-natal days) and late (>7 post-natal days) severe acute kidney injury (AKI) occurrence and duration. Methods A secondary analysis of Preterm Erythropoietin Neuroprotection Trial data. We defined severe AKI (stage 2 or 3) per neonatal modified Kidney Disease: Improving Global Outcomes criteria. Adjusted Cox proportional hazards models were conducted with exposures occurring at least 72 h before severe AKI. Adjusted negative binomial regression models were completed to evaluate risk factors for severe AKI duration. Results Of 923 participants, 2% had early severe AKI. In the adjusted model, gestational diabetes (adjusted HR (aHR) 5.4, 95% CI 1.1–25.8), non-steroidal anti-inflammatory drugs (NSAIDs) (aHR 3.2, 95% CI 1.0–9.8), and vancomycin (aHR 13.9, 95% CI 2.3–45.1) were associated with early severe AKI. Late severe AKI occurred in 22% of participants. Early severe AKI (aHR 2.5, 95% CI 1.1–5.4), sepsis (aHR 2.5, 95% CI 1.4–4.4), vasopressors (aHR 2.9, 95% CI 1.8–4.6), and diuretics (aHR 2.6, 95% CI 1.9–3.6) were associated with late severe AKI. Participants who had necrotizing enterocolitis or received NSAIDs had longer severe AKI duration. Conclusion We identified major risk factors for severe AKI that can be the focus of future research. Impact statement Time-dependent risk factors for severe acute kidney injury (AKI) and its duration are not well defined among infants born <28 weeks’ gestation. Over 1 in 5 infants born <28 weeks’ gestation experienced severe AKI, and this study identified several major time-dependent perinatal risk factors occurring within 72 h prior to severe AKI. This study can support efforts to develop risk stratification and clinical decision support to help mitigate modifiable risk factors to reduce severe AKI occurrence and duration

Preorganized tridentate analogues of mixed hydroxyoxime/carboxylate nickel extractants

Simple tridentate ligands can operate as Ni-extractants in the pH-dependent process: 2LHorg + NiSO4 ⇌ [(L)2Ni]org + H2SO4.</p

Glioma-derived exosomes drive the differentiation of neural stem cells to astrocytes

Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, colony stimulating factor and interleukin 6 of the STAT3 family and Hes family bHLH transcription factor 1 also increased by 2.3, 10, 4.7 and 2.9 fold, respectively. We further examined the effects of these exosomes on rat fetal neural stem cell (rNSC) differentiation using the secreted exosomes from U87 glioma cells or exosomes from U87 cells that were stimulated with interleukin 1β (IL-1β). The rNSCs, extracted from rat brains at embryonic day 14 (E14), underwent a culture protocol that normally leads to predominant (∼90%) differentiation to ODCs. However, in the presence of the exosomes from untreated or IL-1β-treated U87 cells, significantly more cells differentiated into astrocytes, especially in the presence of exosomes obtained from the IL-1β-challenged glioma cells. Moreover, glioma-derived exosomes appeared to inhibit rNSC differentiation into ODCs or astrocytes as indicated by a significantly increased population of unlabeled cells. A portion of the resulting astrocytes coexpressed both CD133 and glial fibrillary acidic protein (GFAP) suggesting that exosomes from U87 cells could promote astrocytic differentiation of NSCs with features expected from a transformed cell. Our data clearly demonstrated that exosomes secreted by human glioma cells provide a strong driving force for rat neural stem cells to differentiate into astrocytes, uncovering potential pathways and therapeutic targets that might control this aggressive tumor type

Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations.

PURPOSE: Mitochondrial disorders are a common cause of inherited metabolic disease and can be due to mutations affecting mitochondrial DNA or nuclear DNA. The current diagnostic approach involves the targeted resequencing of mitochondrial DNA and candidate nuclear genes, usually proceeds step by step, and is time consuming and costly. Recent evidence suggests that variations in mitochondrial DNA sequence can be obtained from whole-exome sequence data, raising the possibility of a comprehensive single diagnostic test to detect pathogenic point mutations. METHODS: We compared the mitochondrial DNA sequence derived from off-target exome reads with conventional mitochondrial DNA Sanger sequencing in 46 subjects. RESULTS: Mitochondrial DNA sequences can be reliably obtained using three different whole-exome sequence capture kits. Coverage correlates with the relative amount of mitochondrial DNA in the original genomic DNA sample, heteroplasmy levels can be determined using variant and total read depths, and-providing there is a minimum read depth of 20-fold-rare sequencing errors occur at a rate similar to that observed with conventional Sanger sequencing. CONCLUSION: This offers the prospect of using whole-exome sequence in a diagnostic setting to screen not only all protein coding nuclear genes but also all mitochondrial DNA genes for pathogenic mutations. Off-target mitochondrial DNA reads can also be used to assess quality control and maternal ancestry, inform on ethnic origin, and allow genetic disease association studies not previously anticipated with existing whole-exome data sets

Clinical and cost-effectiveness of a diabetes education and behavioural weight management programme versus a diabetes education programme in adults with a recent diagnosis of type 2 diabetes: study protocol for the Glucose Lowering through Weight management (GLoW) randomised controlled trial

Introduction: People with type 2 diabetes (T2D) can improve glycaemic control or even achieve remission through weight loss and reduce their use of medication and risk of cardiovascular disease. The Glucose Lowering through Weight management (GLoW) trial will evaluate whether a tailored diabetes education and behavioural weight management programme (DEW) is more effective and cost-effective than a diabetes education (DE) programme in helping people with overweight or obesity and a recent diagnosis of T2D to lower their blood glucose, lose weight and improve other markers of cardiovascular risk. Methods and analysis: This study is a pragmatic, randomised, single-blind, parallel group, two-arm, superiority trial. We will recruit 576 adults with body mass index>25 kg/m2 and diagnosis of T2D in the past 3 years and randomise them to a tailored DEW or a DE programme. Participants will attend measurement appointments at a local general practitioner practice or research centre at baseline, 6 and 12 months. The primary outcome is 12-month change in glycated haemoglobin. The effect of the intervention on the primary outcome will be estimated and tested using a linear regression model (analysis of covariance) including randomisation group and adjusted for baseline value of the outcome and the randomisation stratifiers. Participants will be included in the group to which they were randomised, under the intention-to-treat principle. Secondary outcomes include 6-month and 12-month changes in body weight, body fat percentage, systolic and diastolic blood pressure and lipid profile; probability of achieving good glycaemic control; probability of achieving remission from diabetes; probability of losing 5% and 10% body weight and modelled cardiovascular risk (UKPDS). An intention-to-treat within-trial cost-effectiveness analysis will be conducted from NHS and societal perspectives using participant-level data. Qualitative interviews will be conducted with participants to understand why and how the programme achieved its results and how participants manage their weight after the programme ends. Ethics and dissemination: Ethical approval was received from East of Scotland Research Ethics Service on 15 May 2018 (18/ES/0048). This protocol (V.3) was approved on 19 June 2019. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. Trial registration number: ISRCTN18399564

TP53 mutant MDM2-amplified cell lines selected for resistance to MDM2-p53 binding antagonists retain sensitivity to ionizing radiation

Non-genotoxic reactivation of the p53 pathway by MDM2-p53 binding antagonists is an attractive treatment strategy for wild-type TP53 cancers. To determine how resistance to MDM2/p53 binding antagonists might develop, SJSA-1 and NGP cells were exposed to growth inhibitory concentrations of chemically distinct MDM2 inhibitors, Nutlin-3 and MI-63, and clonal resistant cell lines generated. The p53 mediated responses of parental and resistant cell lines were compared. In contrast to the parental cell lines, p53 activation by Nutlin-3, MI-63 or ionizing radiation was not observed in either the SJSA-1 or the NGP derived cell lines. An identical TP53 mutation was subsequently identified in both of the SJSA-1 resistant lines, whilst one out of three identified mutations was common to both NGP derived lines. Mutation specific PCR revealed these mutations were present in parental SJSA-1 and NGP cell populations at a low frequency. Despite cross-resistance to a broad panel of MDM2/p53 binding antagonists, these MDM2-amplified and TP53 mutant cell lines remained sensitive to ionizing radiation (IR). These results indicate that MDM2/p53 binding antagonists will select for p53 mutations present in tumours at a low frequency at diagnosis, leading to resistance, but such tumours may nevertheless remain responsive to alternative therapies, including IR