Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks

Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (approximate to 20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations-an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise

Pandemic Preparation & Response: A Case Study Applying Kotter’s 8 Step Change Management Theory to Improve Pandemic Response in an Acute Care Setting

For healthcare CEOs and leaders, much time is spent planning and strategically assessing our organizations\u27 overall health and status. Planning cycles vary from 1 year to 5 years and, in some cases, 10-year plans. However, with the onset of the COVID-19 pandemic, healthcare leaders have been forced to pivot and embrace a sense of resilience. Today, we are leading and making decisions on a day-to-day basis and even hour-to-hour based on the uncertainty and needs of our organizations and communities we serve. The crisis of a pandemic requires leadership to act swiftly and with a cadence of assurance to all. We are learning in a time of crisis that some processes work, and others do not. Leaders must meet immediate needs and make changes to the status quo that drives the best results. Kotter’s change management model is an 8-step method for implementing change that can significantly improve operational processes. This case study will demonstrate how change management theory can set the framework and guidelines for a response to a pandemic event and hardwire into a new approach for rapid recovery of operations; thus, creating a standard set of guidelines to meet the demands of future pandemic events, which can assist health system leadership in the future

Prevalence of sociodemographic factors in a cohort of diabetes mellitus: A retrospective study

Exploring the sociodemographic factors of a cohort is a vital phase in revealing significant aspects of the societal health status. The health care sector utilises the results of exploratory analysis of the sociodemographic nature to fulfil various purposes such as constructing health care policies, allocating adequate resources, imposing necessary medications and many more. A large and growing body of evidence shows that understanding the pervasiveness of sociodemographic factors: age, ethnicity, gender, reveal crucial information. Therefore, this study aims to disclose the knowledge through analysing the sociodemographic details of a New Zealand diabetes cohort. Diabetes mellitus is a chronic fatal disease that occurs due to the inability to control proper blood sugar levels, which causes multitudinous acute and chronic complications. Diabetes became a high prevalence disease in the region of Waikato. Analysing the cohort of diabetes patients associated with complications of diabetes illustrate the prevalence of complications of diabetes among the patients. The dataset of the study has been collected from the Waikato district health board. This study intends to report the initial scanning of the dataset profile with visualising the resulting patterns of sociodemographic details from the samples and their association with complications of diabetes. The Sankey diagrams use to visualise the results of exploratory data analysis. The resulted graphs of the data screening descriptively illustrate the characteristics of the cohort associated with demographic factors. Maori population shows higher percentage (0.68) of diabetes patients than the other ethnicities, while having narrower age expansion (13-95) with early onset age, compared to others (20-103). Males (0.61%) are more vulnerable to diabetes than females (0.55%). Additionally, hypertension and cardiovascular diseases are common among the diabetes patients’ in the Waikato region. Maori male population is highly vulnerable to diabetes. This study will be beneficial in constructing and analysing the demographical categories of the cohort to comparatively study the pervasiveness of the diseases among resulting classes

A Hot Saturn Near (but Unassociated with) the Open Cluster NGC 1817

We report on the discovery of a hot Saturn-sized planet (9.916 ± 0.985 R ⊕) around a late F-star, K2-308, observed in Campaign 13 of the K2 mission. We began studying this planet candidate because prior to the release of Gaia DR2, the host star was thought to have been a member (⩾90% membership probability) of the ≈1 Gyr open cluster NGC 1817 based on its kinematics and photometric distance. We identify the host star (among three stars within the K2 photometric aperture) using seeing-limited photometry and rule out false-positive scenarios using adaptive optics imaging and radial velocity observations. We statistically validate K2-308b by calculating a false-positive probability rate of 0.01%. However, we also show using new kinematic measurements provided by Gaia DR2 and our measured radial velocity of the system that K2-308 is unassociated with the cluster NGC 1817. Therefore, the long running search for a giant transiting planet in an open cluster remains fruitless. Finally, we note that our use of seeing-limited photometry is a good demonstration of similar techniques that are already being used to follow up Transiting Exoplanet Survey Satellite (TESS) planet candidates, especially in crowded regions

What then do we do about computer security?

This report presents the answers that an informal and unfunded group at SNL provided for questions concerning computer security posed by Jim Gosler, Sandia Fellow (00002). The primary purpose of this report is to record our current answers; hopefully those answers will turn out to be answers indeed. The group was formed in November 2010. In November 2010 Jim Gosler, Sandia Fellow, asked several of us several pointed questions about computer security metrics. Never mind that some of the best minds in the field have been trying to crack this nut without success for decades. Jim asked Campbell to lead an informal and unfunded group to answer the questions. With time Jim invited several more Sandians to join in. We met a number of times both with Jim and without him. At Jim's direction we contacted a number of people outside Sandia who Jim thought could help. For example, we interacted with IBM's T.J. Watson Research Center and held a one-day, videoconference workshop with them on the questions

Planet Hunters: Assessing the Kepler Inventory of Short Period Planets

We present the results from a search of data from the first 33.5 days of the Kepler science mission (Quarter 1) for exoplanet transits by the Planet Hunters citizen science project. Planet Hunters enlists members of the general public to visually identify transits in the publicly released Kepler light curves via the World Wide Web. Over 24,000 volunteers reviewed the Kepler Quarter 1 data set. We examine the abundance of \geq 2 R\oplus planets on short period (< 15 days) orbits based on Planet Hunters detections. We present these results along with an analysis of the detection efficiency of human classifiers to identify planetary transits including a comparison to the Kepler inventory of planet candidates. Although performance drops rapidly for smaller radii, \geq 4 R\oplus Planet Hunters \geq 85% efficient at identifying transit signals for planets with periods less than 15 days for the Kepler sample of target stars. Our high efficiency rate for simulated transits along with recovery of the majority of Kepler \geq 4 R\oplus planets suggest suggests the Kepler inventory of \geq 4 R\oplus short period planets is nearly complete.Comment: 41 pages,13 figures, 8 tables, accepted to Ap

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Adapting Medical Guidelines to Be Patient-centered Using a Patient-driven Process for Individuals With Sickle Cell Disease and Their Caregivers

Background: Evidence-based guidelines for sickle cell disease (SCD) health maintenance and management have been developed for primary health care providers, but not for individuals with SCD. To improve the quality of care delivered to individuals with SCD and their caregivers, the main purposes of this study were to: (1) understand the desire for patient-centered guidelines among the SCD community; and (2) adapt guideline material to be patient-centered using community-engagement strategies involving health care providers, community -based organizations, and individuals with the disease. Methods: From May–December 2016, a volunteer sample of 107 individuals with SCD and their caregivers gave feedback at community forums (n = 64) and community listening sessions (n = 43) about technology use for health information and desire for SCD-related guidelines. A team of community research partners consisting of community stakeholders, individuals living with SCD, and providers and researchers (experts) in SCD at nine institutions adapted guidelines to be patient-centered based on the following criteria: (1) understandable, (2) actionable, and (3) useful. Results: In community forums (n = 64), almost all participants (91%) wanted direct access to the content of the guidelines. Participants wanted guidelines in more than one format including paper (73%) and mobile devices (79%). Guidelines were adapted to be patient-centered. After multiple iterations of feedback, 100% of participants said the guidelines were understandable, most (88%) said they were actionable, and everyone (100%) would use these adapted guidelines to discuss their medical care with their health care providers. Conclusions: Individuals with SCD and their caregivers want access to guidelines through multiple channels, including technology. Guidelines written for health care providers can be adapted to be patient-centered using Community-engaged research involving providers and patients. These patient-centered guidelines provide a framework for patients to discuss their medical care with their health care providers