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Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.
We characterized 57 isolates from a 2-phase clonal outbreak of New Delhi metallo-β-lactamase–producing Eschericha coli, involving 9 Israeli hospitals; all but 1 isolate belonged to sequence-type (ST) 410. Most isolates in the second phase harbored blaKPC-2 in addition to blaNDM-5. Genetic sequencing revealed most dual-carbapenemase–producing isolates to be monophyletically derived from a common ancestor.
The onset of magnetic reconnection in space, astrophysical and laboratory plasmas is reviewed discussing results from theory, numerical simulations and observations. After a brief introduction on magnetic reconnection and approach to the question of onset, we first discuss recent theoretical models and numerical simulations, followed by observations of reconnection and its effects in space and astrophysical plasmas from satellites and ground-based detectors, as well as measurements of reconnection in laboratory plasma experiments. Mechanisms allowing reconnection spanning from collisional resistivity to kinetic effects as well as partial ionization are described, providing a description valid over a wide range of plasma parameters, and therefore applicable in principle to many different astrophysical and laboratory environments. Finally, we summarize the implications of reconnection onset physics for plasma dynamics throughout the Universe and illustrate how capturing the dynamics correctly is important to understanding particle acceleration. The goal of this review is to give a view on the present status of this topic and future interesting investigations, offering a unified approach.
All drugs abused by humans increase dopamine in the shell of nucleus accumbens, which implicate the neurons of this structure in their hedonic and reinforcing properties. Among the various dopamine receptor subtypes, the D1 (D1R) and D3 (D3R) receptors co-localise in accumbal shell neurons. Synergistic D1R/D3R interactions at this level were found on gene expression and during induction and expression of behavioral sensitisation to levodopa in rats bearing unilateral lesions of dopamine neurons. Behavioral sensitisation to abused drugs is a component of their long-term effects. Converging pharmacologic, human postmortem and genetic studies suggest the involvement of the D3R in reinforcing effects of drugs; D3R agonists reduced cocaine self-administration in rats, without disrupting the maintenance of self-administration. These data suggest the use of D3R agonists as partial substitutes to treat cocaine dependence, by affecting its reward component. However, substitution therapies maintain dependence and may be inefficient on drug craving and relapse, which are the unsolved and critical problems in the treatment of drug addiction. Recently, a highly selective and partial D3R agonist was shown to reduce cocaine-associated cue-controlled behaviour in rats, without having any primary intrinsic effects. As drug-associated cues maintain drug-seeking in animals and elicit craving and relapse in humans, such D3R agents have potential therapeutic applications.
The objective of this study was to evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania.
Male and female subjects with bipolar I disorder with MRS 3 14 were enrolled. Subjects achieving ≥ 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or divalproex were randomized into the 6-month double-blind maintenance period, to ziprasidone + mood stabilizer or placebo + mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode, and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (Log-rank test).
127 and 112 subjects were randomized to and treated in the ziprasidone and placebo groups, respectively. The time to intervention for a mood episode was significantly different, favoring ziprasidone (p = 0.0104). 19.7% and 32.4% of ziprasidone and placebo subjects, respectively, required intervention for a mood episode. Time to discontinuation for any reason was significantly different (p = 0.0047), favoring ziprasidone. Among treatment-emergent adverse events occurring in the double-blind period, the only event occurring more frequently in the ziprasidone group than in the placebo group (≥ 5%) was tremor (6.3% vs 3.6%, respectively).
These results demonstrate that ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
We present the first images of a coordinated campaign to follow active region NOAA 12709 on 2018 May 13 as part of a joint effort between three observatories (China-Europe). The active region was close to disk center and enclosed a small pore, a tight polarity inversion line and a filament in the chromosphere. The active region was observed with the 1.5-meter GREGOR solar telescope on Tenerife (Spain) with spectropolarimetry using GRIS in the He i 10830 Å spectral range and with HiFI using two broad-band filter channels. In addition, the Lomnicky Stit Observatory (LSO, Slovakia) recorded the same active region with the new Solar Chromospheric Detector (SCD) in spectroscopic mode at Hα 6562 Å. The third ground-based telescope was located at the Fuxian Solar Observatory (China), where the active region was observed with the 1-meter New Vacuum Solar Telescope (NVST), using the Multi-Channel High Resolution Imaging System at Hα 6562 Å. Overlapping images of the active region from all three telescopes will be shown as well as preliminary Doppler line-of-sight (LOS) velocities. The potential of such observations are discussed.
The aim of this study was to compare the effect of Hurricane Maria on internalizing and posttraumatic stress disorders (PTSD) among Puerto Ricans who moved to Florida after the storm versus those who stayed on the island.
In March through April 2018 (6 months after Hurricane Maria), an online survey was used to assess the effects of the storm on mental health. A sample of 213 displaced Puerto Ricans living in urban and rural/suburban areas in Florida, as well as urban and rural areas of Puerto Rico, participated in the study.
Rates of PTSD were high in both sites (Florida, 65.7%; Puerto Rico, 43.6%); however, participants in Florida were far more likely than those in Puerto Rico to meet diagnostic criteria for PTSD (OR, 2.94; 95% CI, 1.67-5.26). Among participants in both Florida and Puerto Rico, those living in urban areas were more likely than those in rural/suburban areas to meet criteria for PTSD and generalized anxiety disorder.
Results suggest that post-Hurricane Maria adjustment and adaptation may have been more psychologically taxing for Puerto Ricans who moved to Florida than it was for those who remained on the island, and more difficult for those in urban areas than it was for those in suburban or rural areas. (Disaster Med Public Health Preparedness. 2019;13:24–27)
Despite the recent increase in attention given to Archbishop Wulfstan and his writings, the so-called ‘Laws of Edward and Guthrum’ – a lawcode forged by the archbishop in the opening years of the eleventh century – has received little analysis since Dorothy Whitelock’s 1941 study established the churchman as its true author. My article seeks to fill this gap firstly by expanding on Whitelock’s article. I show that many more of the text’s clauses function as antecedents to Wulfstan’s later legislation than those she identified in her important article. Second, I argue that §10 of the code, a clause not repeated in the archbishop’s later legislation, surely still held legal authority given Wulfstan’s prescriptions for non-lethal punishment in some cases. Finally, I posit that Wulfstan’s attribution of the code to Alfred, seen in its opening, reflects the archbishop’s value of him as a king worth emulating.
This pilot study aimed to assess the community needs and population health status for the low-income town of Punta Santiago, situated on the southeastern coast of Puerto Rico at the point where Hurricane Maria made landfall on September 20, 2017.
A cross-sectional, interviewer-administered survey was conducted 6 months after the storm with a representative random sample of 74 households. The survey characterized population demographics and resident needs in relation to storm damage and disruption. The survey also assessed prevalence and symptom severity of major depression, generalized anxiety, and posttraumatic stress disorder.
Most of Punta Santiago was without electrical power and more than half of households sustained severe damage. Residents reported loss of jobs, decreased productivity, school closures, dependency on aid for basic necessities, increased risk for vector-borne diseases, unrelenting exposure to heat and humidity, and diminished health status. Two-thirds (66.2%) of the respondents had clinically significant symptom elevations for at least 1 of the 3 common mental disorders assessed: major depression, generalized anxiety, or posttraumatic stress disorder.
Pilot survey results, along with other studies conducted in Punta Santiago, can be used to provide guidance for interventions with this community as well as with other low-income, storm-affected areas. (Disaster Med Public Health Preparedness. 2019;13:18–23)
The Single Ventricle Reconstruction trial randomised neonates with hypoplastic left heart syndrome to a systemic-to-pulmonary-artery shunt strategy. Patients received care according to usual institutional practice. We analysed practice variation at the Stage II surgery to attempt to identify areas for decreased variation and process control improvement.
Prospectively collected data were available in the Single Ventricle Reconstruction public-use database. Practice variation across 14 centres was described for 397 patients who underwent Stage II surgery. Data are centre-level specific and reported as interquartile ranges across all centres, unless otherwise specified.
Preoperative Stage II median age and weight across centres were 5.4 months (interquartile range 4.9–5.7) and 5.7 kg (5.5–6.1), with 70% performed electively. Most patients had pre-Stage-II cardiac catheterisation (98.5–100%). Digoxin was used by 11/14 centres in 25% of patients (23–31%), and 81% had some oral feeds (68–84%). The majority of the centres (86%) performed a bidirectional Glenn versus hemi-Fontan. Median cardiopulmonary bypass time was 96 minutes (75–113). In aggregate, 26% of patients had deep hypothermic circulatory arrest >10 minutes. In 13/14 centres using deep hypothermic circulatory arrest, 12.5% of patients exceeded 10 minutes (8–32%). Seven centres extubated 5% of patients (2–40) in the operating room. Postoperatively, ICU length of stay was 4.8 days (4.0–5.3) and total length of stay was 7.5 days (6–10).
In the Single Ventricle Reconstruction Trial, practice varied widely among centres for nearly all perioperative factors surrounding Stage II. Further analysis may facilitate establishing best practices by identifying the impact of practice variation.
Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure performed in patients with life-threatening conditions, but can be associated with complications. The objectives of this study are to evaluate data on national practice patterns and complications rates in order to optimize clinical care Methods: The Canadian Neurosurgery Research Collaborative conducted a prospective multi-centre registry of patients undergoing EVD insertions at Canadian residency programs Results: In this interim analysis, 4 sites had recruited 46 patients (mean age: 53.9 years, male:female 2:1). Most EVD insertions occurred outside of the operating theatre, using free-hand technique, and performed by junior neurosurgery residents (R1-R3). The catheter tip was in the ipsilateral frontal horn or body of the lateral ventricle in 76% of cases. Suboptimally placed catheters did not have higher rates of short-term occlusion. EVD-related hemorrhage occurred in 6.5% (3/45) with only 1 symptomatic patient. EVD-related infection occurred in 13% (6/46) at a mean of 6 days and was associated with longer duration of CSF drainage (P=0.039; OR: 1.13) Conclusions: Interim results indicate rates of EVD-related complications may be higher than previously thought. This study will continue to recruit patients to confirm these findings and determine specific risk factors associated with them
Background: No standardized method of resident operative-case logging exists. Our study sought to develop a standardized form used by residents to log operative-cases. Methods: Members of the Canadian Neurosurgery Research Collaborative (CNRC), a national resident-led research organization have created a standardized document based on the current Royal College objectives for operative procedures (section 5). Modifications to structure and content will be guided via consensus from Canadian neurosurgery program-directors. Results: Program directors in each CNRC collaborative institution will be asked to modify the standardized form. The CNRC currently involves thirteen of the fourteen Canadian neurosurgery residency programs. Additional consensus, if necessary, can be reached at the Royal College meeting for program directors of neurosurgery March 20th 2017. Conclusions: A standardized operative-case log represents the first step in a prospective study towards compiling operative volume of all Canadian neurosurgical residents over one academic year. Such data will be essential to guide informed decisions with regard to Royal College requirements as Canadian neurosurgical programs transition to a competency based framework.
Background: Communicating with senior neurosurgical colleagues during residency necessitates a reliable and versatile smartphone. Smartphones and their apps are commonplace. They enhance communication with colleagues, provide the ability to access patient information and results, and allow access to medical reference applications. Patient data safety and compliance with the Personal Health Information Protection Act (PHIPA, 2004) in Canada remain a public concern that can significantly impact the way in which mobile smartphones are utilized by resident physicians Methods: Through the Canadian Neurosurgery Research Collaborative (CNRC), an online survey characterizing smartphone ownership and utilization of apps among Canadian neurosurgery residents and fellows was completed in April 2016. Results: Our study had a 47% response rate (80 surveys completed out of 171 eligible residents and fellows). Smartphone ownership was almost universal with a high rate of app utilization for learning and facilitating the care of patients. Utilization of smartphones to communicate and transfer urgent imaging with senior colleagues was common. Conclusions: Smartphone and app utilization is an essential part of neurosurgery resident workflow. In this study we characterize the smartphone and app usage within a specialized cohort of residents and suggest potential solutions to facilitate greater PHIPA adherence
Background: The Canadian Neurosurgery Research Collaborative (CNRC) was founded in November 2015 as a resident-led national network for multicentre research. We present an annual report of our activities. Methods: CNRC meetings and publications were reviewed and summarized. The status of ongoing and future studies was collected from project leaders. Results: In its first year, the CNRC produced two papers accepted for publication in the Canadian Journal of Neurological Sciences: A CNRC launch letter and a study of operative volume at Canadian neurosurgery residency programs. Three manuscripts are in preparation: 1) a study of the demographics of Canadian neurosurgery residents, 2) an assessment of mobile devices usage patterns and 3) a validation study of the most utilized neurosurgery mobile apps. In addition, protocols for two multi-centre studies are currently undergoing national Research Ethics Board review: A retrospective study of the incidence and predictors of cerebellar mutism and a prospective registry of external ventricular drain procedures and complications. The network is now a registered not-for-profit organization endorsed by the Canadian Neurosurgical Society. Conclusions: The CNRC is a feasibile, relevant and productive resident-led national research network. As the CNRC matures, we look forward to expanding the scope and impact of its projects.
Background: The Canadian Neurosurgery Research Collaborative (CNRC) is a new consortium of neurosurgery residency programs set-up to facilitate the planning and implementation of multi-center studies. As a trainee-led organization, it will focus on resident-initiated, resident-driven projects. The goal of this study is to assess the demographics of Canadian neurosurgery residents, with particular focus on their academic and subspecialty interests. Methods: After approval by the CNRC, an online survey will be sent to all Canadian neurosurgery residents and fellows with reminders at 2, 4 and 6 weeks. Anonymous, basic demographic data will be collected. Specific interest towards the various subspecialties, research and academic vs community practice will be measured. The data will be crossed with the ongoing Canadian Neurosurgery Operative Landscape study to assess the impact of case volume on academic and subspecialty interests. Results: This is the first study providing a snapshot of Canadian neurosurgery residents at all levels of training. The study is ongoing and the official results will be presented at the meeting. As one of the first CNRC studies, it will also demonstrate the effectiveness of the collaborative. Conclusions: Understanding the demographics and interests of Canadian neurosurgery residents will allow the CNRC to better fulfill its mission.