Indigenous research methods for healing sexual trauma with Cree women.

In this study, exploratory research on self-determination using Indigenous research methods provided a model to help heal trauma and discuss recovery for traumatic sexual experiences. The methods and healing were based on a Cree worldview. Informed consent and questions were developed by the principal investigator prior to the research commencing. Eleven co-creators had the opportunity to revise questions, discuss the research, speak the Cree language, and participate in one-to-one interviews, group meetings and ceremonies. They also had the chance to review the transcripts and approve/disapprove the content, provide guidance on sacred knowledge and suggest terms to use, and co-author the paper, if they chose and three did. A Cree concept was developed from the work, namely, nehiyaw isecikewena which involved promoting self-determination and sovereignty alongside recovery.

Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML.

PURPOSE: Gilteritinib is a type 1 FLT3 inhibitor active as monotherapy for relapsed or refractory FLT3-mutated AML. We investigated the safety, tolerability, and efficacy of gilteritinib incorporated into intensive induction and consolidation chemotherapy, and as maintenance therapy for adult patients with newly diagnosed, non-favorable-risk AML. METHODS: In this phase IB study (2215-CL-0103; ClinicalTrials.gov identifier: NCT02236013), 103 participants were screened and 80 were allocated to treatment. The study was divided into four parts: dose escalation, dose expansion, investigation of alternate anthracycline and gilteritinib schedule, and continuous gilteritinib during consolidation. RESULTS: After dose escalation, 120 mg gilteritinib once daily was chosen for further study. There were 58 participants evaluable for response at this dose, 36 of whom harbored FLT3 mutations. For participants with FLT3-mutated AML, the composite complete response (CRc) rate was 89% (83% were conventional complete responses), all achieved after a single induction cycle. The median overall survival time was 46.1 months. Gilteritinib was well-tolerated in this context although the median time to count recovery during induction was approximately 40 days. Longer time-to-count recovery was associated with higher trough levels of gilteritinib, which, in turn, were associated with azole use. The recommended regimen is gilteritinib at a dose of 120 mg once daily from days 4 to 17 or 8 to 21 of a 7 + 3 induction with either idarubicin or daunorubicin and from day 1 continuously with high-dose cytarabine consolidation. Maintenance therapy with gilteritinib was well-tolerated. CONCLUSION: These results demonstrated the safety and tolerability of gilteritinib incorporated into an induction and consolidation chemotherapy regimen, and as single-agent maintenance therapy for patients with newly diagnosed FLT3-mutant AML. The data herein provide an important framework for the design of randomized trials comparing gilteritinib with other FLT3 inhibitors.

Minimising prescription errors-a quality improvement project in the ophthalmology department in a tertiary referral hospital.

PURPOSE: The aim of this quality improvement project was to look into the hospital prescriptions and to identify and record the type and number of errors, to implement measures to reduce the risk of these errors and then to reaudit to assess the impact of changes implemented. METHODS: The initial audit was conducted prospectively over a eleven-week period. Prescriptions written by doctors of all grades and members of the staff, such as optometrists and nurses, were analysed. A glaucoma prescription guide along with more training at prescribing for doctors was introduced with a view to reducing these errors. A reaudit later demonstrated a significant reduction in these errors. RESULTS: After the introduction of a glaucoma prescription guide and more training for all grades of staff members, prescription errors reduced to 73/2342 (3.1%). Reaudit showed a reduction in both prescription writing errors 50/73(68.4%) and drug-related errors 23/73(31.6%). CONCLUSION: Prescription errors are avoidable. This audit demonstrated that providing an accessible, easy to read and understand glaucoma prescription guide in the outpatient department along with targeted training for medical staff in prescribing can help in minimising these errors and can lead to safer practice.

Pharmacokinetic Profile of Gilteritinib: A Novel FLT-3 Tyrosine Kinase Inhibitor.

BACKGROUND AND OBJECTIVE: Gilteritinib is a novel, highly selective tyrosine kinase inhibitor approved in the USA, Canada, Europe, Brazil, Korea, and Japan for the treatment of FLT3 mutation-positive acute myeloid leukemia. This article describes the clinical pharmacokinetic profile of gilteritinib. METHODS: The pharmacokinetic profile of gilteritinib was assessed from five clinical studies. RESULTS: Dose-proportional pharmacokinetics was observed following once-daily gilteritinib administration (dose range 20-450 mg). Median maximum concentration was reached 2-6 h following single and repeat dosing of gilteritinib; mean elimination half-life was 113 h. Elimination was primarily via feces. Exposure to gilteritinib was comparable under fasted and fed conditions. Gilteritinib is primarily metabolized via cytochrome P450 (CYP) 3A4; coadministration of gilteritinib with itraconazole (a strong P-glycoprotein inhibitor and CYP3A4 inhibitor) or rifampicin (a strong P-glycoprotein inducer and CYP3A inducer) significantly affected the gilteritinib pharmacokinetic profile. No clinically relevant interactions were observed when gilteritinib was coadministered with midazolam (a CYP3A4 substrate) or cephalexin (a multidrug and toxin extrusion 1 substrate). Unbound gilteritinib exposure was similar between subjects with hepatic impairment and normal hepatic function. CONCLUSIONS: Gilteritinib exhibits a dose-proportional pharmacokinetic profile in healthy subjects and in patients with relapsed/refractory acute myeloid leukemia. Gilteritinib exposure is not significantly affected by food. Moderate-to-strong CYP3A inhibitors demonstrated a significant effect on gilteritinib exposure. Coadministration of gilteritinib with CYP3A4 or multidrug and toxin extrusion 1 substrates did not impact substrate concentrations. Unbound gilteritinib was comparable between subjects with hepatic impairment and normal hepatic function; dose adjustment is not warranted for patients with hepatic impairment. CLINICAL TRIAL REGISTRATION: NCT02014558, NCT02456883, NCT02571816.

An examination of financial capacity and neuropsychological performance in chronic acquired brain injury (CABI).

PRIMARY OBJECTIVE: Financial Capacity (FC) is known to be impaired in the acute and subacute stages of brain injury. The current study sought to examine FC in the context of chronic, moderate to severe acquired brain injury (CABI). RESEARCH DESIGN: The Financial Competence Assessment Inventory (FCAI), developed in Australia, was adapted to examine the integrity of FC in an American sample. METHODS AND PROCEDURES: Healthy comparison (HC) participants were recruited from the community, whereas participants with CABI were recruited from a community-based rehabilitation center. Participants completed the FCAI and a neuropsychological battery. FCAI performance in the current study was compared against previously published Australian data. Multiple regression analyses examined group (CABI vs. HC) as a predictor of FC. Bivariate correlations examined the cognitive correlates of FCAI in the CABI group. MAIN OUTCOMES AND RESULTS: The HC group in the current study obtained similar mean scores as those in the Australian sample. CABI group membership predicted lower performance on each FCAI dimension. In the CABI group, attention, working memory, delayed verbal memory, abstract reasoning and impulsivity were uniquely associated with FCAI dimensions. CONCLUSIONS: Findings underscore the importance of continued monitoring of FC even after the subacute stage of injury, and identify cognitive impairments that may be particularly detrimental for specific dimensions of FC.

Multistate Infestation with the Exotic Disease-Vector Tick Haemaphysalis longicornis - United States, August 2017-September 2018.

Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017 (1). This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six species of domestic animals, six species of wildlife, and humans. To forestall adverse consequences in humans, pets, livestock, and wildlife, several critical actions are indicated, including expanded surveillance to determine the evolving distribution of H. longicornis, detection of pathogens that H. longicornis currently harbors, determination of the capacity of H. longicornis to serve as a vector for a range of potential pathogens, and evaluation of effective agents and methods for the control of H. longicornis.

Informant Report of Financial Capacity for Individuals With Chronic Acquired Brain Injury: An Assessment of Informant Accuracy.

OBJECTIVE: Primarily, to investigate the association between informant report and objective performance on specific financial capacity (FC) tasks by adults with chronic, moderate to severe acquired brain injury, and to examine the nature of misestimates by the informants. DESIGN: Cross-sectional design. SETTING: A postacute, community-based rehabilitation center. PARTICIPANTS: Data were obtained from 22 chronic acquired brain injury (CABI) adults, mean age of 46.6 years (SD = 8.67), mean years of education of 13.45 years (SD = 2.15), with moderate to severe acquired brain injury (86% had traumatic brain injury), with a mean postinjury period of 17.14 years (SD = 9.5). Whereas the CABI adults completed the Financial Competence Assessment Inventory interview-a combination of self-report and performance-based assessment, 22 informants completed a specifically designed parallel version of the interview. RESULTS: Pearson correlations and 1-sample t tests based on the discrepancy scores between informant report and CABI group's performance were used. The CABI group's performance was not associated with its informant's perceptions. One-sample t tests revealed that informants both underestimated and overestimated CABI group's performance. CONCLUSIONS: Results indicate lack of correspondence between self- and informant ratings. Further investigation revealed that misestimations by informants occurred in contrary directions with CABI adults' performance being inaccurately rated. These findings raise critical issues related to assuming that the informant report can be used as a "gold standard" for collecting functional data related to financial management, and the idea that obtaining objective data on financial tasks may represent a more valid method of assessing financial competency in adults with brain injury.

Challenges and Opportunities in the Development of Medical Therapies for Pediatric Populations and the Role of Extrapolation.

Extrapolation can be used to address challenges in pediatric drug development. This review describes how these challenges could be addressed by further evolution of quantitative frameworks (i.e., model-based/informed drug discovery and development) and regulatory science in support of pediatric drug development. Included are examples of diseases/indications where extrapolation has been used in different ways as a basis for identifying gaps in the framework and opportunities for continued advancement of pediatric drug development.

Spatial distribution of counties in the continental United States with records of occurrence of Amblyomma americanum (Ixodida: Ixodidae).

In addition to being a major nuisance biter, the lone star tick, Amblyomma americanum (L.), is increasingly recognized as an important vector of pathogens affecting humans, domestic animals, and wildlife. Despite its notoriety, efforts have been lacking to define the spatial occurrence ofA. americanum in the continental United States with precision beyond that conveyed in continental-scale distribution maps. Here we present a county-level distribution map for A. americanum generated by compiling collection records obtained from a search of the published literature and databases managed by the USDA, U.S. National Tick Collection, and Walter Reed Biosystematics Unit. Our decadal and cumulative maps, which visually summarize 18,121 collections made between 1898 and 2012, show that A. americanum is either established (> or = six ticks or -two life stages) or reported (

Youth researching youth: benefits, limitations and ethical considerations within a participatory research process.

OBJECTIVES: To examine the benefits, limitations and ethical issues associated with conducting participatory research on tobacco use using youth to research other youth. STUDY DESIGN: Community-based participatory research. METHODS: Research on tobacco use was conducted with students in the K'àlemì Dene School and Kaw Tay Whee School in the Northwest Territories, Canada, using PhotoVoice. The Grade 9-12 students acted as researchers. Researcher reflections and observations were assessed using "member checking," whereby students, teachers and community partners could agree or disagree with the researcher's interpretation. The students and teachers were further asked informally to share their own reflections and observations on this process. RESULTS AND CONCLUSIONS: Using youth to research other youth within a participatory research framework had many benefits for the quality of the research, the youth researchers and the community. The research was perceived by the researchers and participants to be more valid and credible. The approach was more appropriate for the students, and the youth researchers gained valuable research experience and a sense of ownership of both the research process and results. Viewing smoking through their children's eyes was seen by the community to be a powerful and effective means of creating awareness of the community environment. Limitations of the approach were residual response bias of participants, the short period of time to conduct the research and failure to fully explore student motivations to smoke or not to smoke. Ethical considerations included conducting research with minors, difficulties in obtaining written parental consent, decisions on cameras (disposable versus digital) and representation of all participants in the final research product.

Diversity and activity of free-living nitrogen-fixing bacteria and total bacteria in organic and conventionally managed soils.

Agricultural soils are heterogeneous environments in which conditions affecting microbial growth and diversity fluctuate widely in space and time. In this study, the molecular ecology of the total bacterial and free-living nitrogen-fixing communities in soils from the Nafferton Factorial Systems Comparison (NFSC) study in northeast England were examined. The field experiment was factorial in design, with organic versus conventional crop rotation, crop protection, and fertility management factors. Soils were sampled on three dates (March, June, and September) in 2007. Total RNA was extracted from all soil samples and reverse transcribed. Denaturing gradient gel electrophoresis (DGGE) and quantitative PCR (qPCR) were used to analyze nifH and 16S rRNA genes in order to study free-living diazotrophs and the total bacterial community, respectively. Crop rotation was shown to have a significant effect on total bacterial diversity (and that of free-living N fixers) (P ≤ 0.001). On all three dates, nifH activity was higher in the conventional crop rotation. In contrast, qPCR analysis of free-living N fixers indicated significantly higher levels of activity in conventionally fertilized plots in June (P = 0.0324) and in plots with organic crop protection in September (P = 0.0143). To our knowledge, the effects of organic and conventional farming systems on free-living diazotrophs have never been studied. An increased understanding of the impacts of management practices on free-living N fixers could allow modifications in soil management practices to optimize the activity of these organisms.

A Rift Valley fever risk surveillance system for Africa using remotely sensed data: potential for use on other continents.

The authors developed a monitoring and risk mapping system using normalized difference vegetation index (NDVI) times series data derived from the advanced very high resolution radiometer (AVHRR) instrument on polar orbiting national oceanographic and atmospheric administration (NOAA) satellites to map areas with a potential for a Rift Valley fever (RVF) outbreaks in sub-Saharan Africa. This system is potentially an important tool for local, national and international organisations involved in the prevention and control of animal and human disease, permitting focused and timely implementation of disease control strategies several months before an outbreak. We are currently developing a geographic information system (GIS)-based remotely sensed early warning system for potential RVF vectors in the United States. Forecasts of the potential emergence of mosquito vectors will be disseminated throughout the United States, providing several months' warning in advance of potentially elevated mosquito populations. This would allow timely, targeted implementation of mosquito control, animal quarantine and vaccine strategies to reduce or prevent animal and human disease.

The evolution of internet-based map server applications in the United States Department of Agriculture, Veterinary Services.

The internet is used increasingly as an effective means of disseminating information. For the past five years, the United States Department of Agriculture (USDA) Veterinary Services (VS) has published animal health information in internet-based map server applications, each oriented to a specific surveillance or outbreak response need. Using internet-based technology allows users to create dynamic, customised maps and perform basic spatial analysis without the need to buy or learn desktop geographic information systems (GIS) software. At the same time, access can be restricted to authorised users. The VS internet mapping applications to date are as follows: Equine Infectious Anemia Testing 1972-2005, National Tick Survey tick distribution maps, the Emergency Management Response System-Mapping Module for disease investigations and emergency outbreaks, and the Scrapie mapping module to assist with the control and eradication of this disease. These services were created using Environmental Systems Research Institute (ESRI)'s internet map server technology (ArcIMS). Other leading technologies for spatial data dissemination are ArcGIS Server, ArcEngine, and ArcWeb Services. VS is prototyping applications using these technologies, including the VS Atlas of Animal Health Information using ArcGIS Server technology and the Map Kiosk using ArcEngine for automating standard map production in the case of an emergency.

Distribution, seasonality, and hosts of the Rocky Mountain wood tick in the United States.

Anaplasma marginale Theiler is a tick-borne pathogen that causes anaplasmosis in cattle. There are approximately 20 tick species worldwide that are implicated as vectors of this pathogen. In the United States, Dermacentor andersoni Stiles and Dermacentor variabilis (Say) are the principal vectors. The risk of transmission of anaplasmosis to cattle has been largely based on the distribution of D. andersoni in the United States. We developed a centralized geographic database that incorporates collection records for D. andersoni from two large national databases. We reviewed the geographic records in each database and postings from MEDLINE and AGRICOLA to produce a national county-level distribution map based on a total of 5,898 records. The records spanned the period from 1903 through 2001 with the majority between 1921 to 1940. Populations of D. andersoni were recorded from 267 counties in 14 states and were distinguished as either established or reported. We found 180 counties with established populations of D. andersoni and 87 counties with reported occurrences in 14 states with the majority of established populations reported from Montana, Idaho, and Oregon. D. andersoni populations in the United States currently extend from the western portions of Nebraska and the Dakotas westward to the Cascade Mountains and from the northern counties of Arizona and New Mexico northward to the Canadian border. The data will be useful for identifying regions at increased risk of acquiring anaplasmosis in the United States. Based upon the database collection records, we also present a summary of recorded hosts for D. andersoni and comments on its seasonal occurrence.

Experimental transmission of West Nile virus (Flaviviridae: Flavivirus) by Carios capensis ticks from North America.

Seabird soft ticks, Carios capensis (Ixodida: Argasidae), originally collected from coastal Georgia, USA, were allowed to ingest a blood meal from pekin ducklings (Anas domesticus) infected with WNV. After 35 days of extrinsic incubation, the ticks transmitted virus to naive ducklings. WNV was detected via plaque assay and RTPCR in ticks and in tissues and serum of ducklings 7 days post infestation.

Prevalence of borrelia burgdorferi sensu lato infection among rodents and host-seeking ticks in South Carolina.

Tissues of rodents and host-seeking adult ticks collected in the Piedmont, Sandhills, Coastal Plain, and Coastal Zone of South Carolina were cultured in attempts to isolate Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt & Brenner), the etiologic agent of Lyme disease. An exploratory, tree-based statistical analysis was used to identify ecological variables that were associated with spirochete infection among rodents and ticks. Spirochetes were isolated from tissues of 71 rodents: 22 (69%) of 32 eastern woodrats, 39 (53%) of 74 cotton mice, and 11(25%) of 44 hispid cotton rats. Rodent infection prevalences were significantly higher in the Coastal Zone than in other regions. Spirochetes were also cultured from 31 (2.6%) of 1,193 questing ticks. Prevalence of spirochetes in Ixodes affinis Neumann (19/74, 26%) was significantly higher than in I. scapularis Say (12/864, 1.3%) and other species (0/255) of ticks tested. In addition, two (9%) of 23 adult I. minor Neumann removed from woodrats contained spirochetes. Isolates from rodents and ticks were analyzed immunologically by indirect immunofluorescence and Western blots, and further characterized by polymerase chain reaction assays and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All were determined to be B. burgdorferi sensu lato. Results of this study confirmed that B. burgdorferi is endemic in South Carolina, and that enzootic transmission cycles exist at foci in the Coastal Zone. These findings add additional evidence that I. affinis and I. minor are potentially significant maintenance vectors of the spirochete.