The Effect of Socioeconomic Status and Race/Ethnicity on the Risk of Presenting With Advanced Stage at Diagnosis in Embryonal Tumors.

We evaluated whether socioeconomic status (SES), race/ethnicity, and their interaction were associated with the presentation of advanced stage at diagnosis in embryonal tumors. Children 0 to 19 years of age diagnosed with embryonal tumors between 2006 and 2018 were identified from the US Surveillance, Epidemiology, and End Results program database specialized with Census Tract SES/Rurality. SES quintile was derived from a composite index for census tracts. We performed logistic regression to estimate odds ratios (ORs) and 95% confidence intervals by SES and race/ethnicity, adjusting for sex, age, and diagnosis year. Overall, no significant associations were found between either SES or race/ethnicity and the risk of presenting with advanced stage at diagnosis, although patterns of risk reductions were observed in atypical teratoid/rhabdoid tumors and embryonal rhabdomyosarcoma with increasing SES. In the stratified analysis, decreased odds of presenting with advanced-stage embryonal rhabdomyosarcoma were observed for Hispanics with higher SES (OR: 0.24, 95% Confidence Interval: 0.08-0.75) compared with Hispanics with lower SES. Future studies incorporating individual-level SES, cancer-specific staging information, and potential demographic, clinical, epidemiological, and genetic risk factors are warranted to confirm our findings.

A legal dispute resolution intervention for patients with substance use disorders: a study protocol for a randomized controlled trial.

BACKGROUND: Substance use disorders (SUDs) represent major public health concerns and are linked to enhanced risk of legal consequences. Unresolved legal issues may prevent individuals with SUD from completing treatment. Interventions aimed at improving SUD treatment outcomes are limited. Filling that gap, this randomized controlled trial (RCT) tests the ability of a technology-assisted intervention to increase SUD treatment completion rates and improve post-treatment health, economic, justice-system, and housing outcomes. METHODS: A randomized controlled trial with a two-year administrative follow-up period will be conducted. Eight hundred Medicaid eligible and uninsured adults receiving SUD treatment will be recruited at community-based non-profit health care clinics in Southeast, Michigan, USA. Using an algorithm embedded in a community-based case management system, we randomly assign all eligible adults to one of two groups. The treatment/intervention group will receive hands-on assistance with a technology aimed at resolving unaddressed legal issues and the control group receives no treatment. Upon enrollment into the intervention, both treatment (n = 400) and control groups (n = 400) retain traditional options to resolve unaddressed legal issues, such as hiring an attorney, but only the treatment group is targeted the technology and offered personalized assistance in navigating the online legal platform. To develop baseline and historical contexts for participants, we collect life course history reports from all participants and intend to link those in each group to administrative data sources. In addition to the randomized controlled trial (RCT), we used an exploratory sequential mixed methods and participatory-based design to develop, test, and administer our life course history instruments to all participants. The primary objective is to test whether targeting no-cost online legal resources to those experiencing SUD improves their long-term recovery and decreases negative health, economic, justice-system, and housing outcomes. DISCUSSION: Findings from this RCT will improve our understanding of the acute socio-legal needs faced by those experiencing SUD and provide recommendations to help target resources toward the areas that best support long-term recovery. The public health impact includes making publicly available a deidentified, longitudinal dataset of uninsured and Medicaid eligible clients in treatment for SUD. Data include an overrepresentation of understudied groups including African American and American Indian Alaska Native persons documented to experience heightened risk for SUD-related premature mortality and justice-system involvement. Within these data, several intended outcome measures can inform the health policy landscape: (1) health, including substance use, disability, mental health diagnosis, and mortality; (2) financial health, including employment, earnings, public assistance receipt, and financial obligations to the state; (3) justice-system involvement, including civil and criminal legal system encounters; (4) housing, including homelessness, household composition, and homeownership. TRIAL REGISTRATION: Retrospectively registered # NCT05665179 on December 27, 2022.

Exploration of genetic ancestry and socioeconomic status in the incidence of neuroblastoma: An ecological study.

Although global differences in the incidence of neuroblastoma have been examined, the underlying mechanism has yet to be elucidated. Previous studies have suggested genetic ancestry and human development index (HDI) as contributing factors, but few studies have been conducted at the international level. Here, we aimed to examine whether the frequency of common genomic variation associated with neuroblastoma can affect its risk at the ecological level with consideration of the HDI. Minor allele frequencies (MAFs) for 22 single-nucleotide polymorphisms (SNPs) were abstracted from the Geography of Genetic Variants Browser. The number of incident neuroblastomas for each population was obtained from the Cancer Incidence in Five Continents series. Further, population pseudo-polygenic risk scores (pp-PRSs) were calculated as a sum of MAFs at the population level, each of which was weighted by effect sizes from prior studies. Negative binomial regression was used to estimate the incidence rate ratios (IRRs) and the 95% confidence intervals (CIs) to examine whether differences in MAFs across the population influence the risk of neuroblastoma, with and without adjustment for HDI and whether pp-PRSs can be a predictor of the risk of neuroblastoma. Overall, our results indicated that the neuroblastoma risk associated with variation in SNP frequency could not be differentiated from that of HDI at the ecological level. Additionally, pp-PRSs were not significantly associated with the risk of neuroblastoma (IRR: 0.99, 95% CI: 0.62-1.60). Further study using individual-level data is warranted to minimize the bias related to the use of population-level data in this study.

Exploratory Study of Cat Adoption in Families of Children with Autism: Impact on Children's Social Skills and Anxiety.

PURPOSE: The diagnosis of Autism Spectrum Disorder (ASD) occurs in one in 54 children and companion animals (CA) are common in families of children with ASD. Despite evidence of CA ownership benefits for children with ASD, little is known about cats. The purpose was to explore the impact of shelter cat adoption by families of children with ASD. DESIGN AND METHODS: This was the first randomized controlled trial of adoption of a temperament screened cat by families of children with ASD. Families assigned to the treatment group adopted a cat and were followed for 18 weeks. Families assigned to the control group were followed for 18 weeks without intervention, then converted to treatment, by adopting a cat and were followed another 18 weeks. Adopted cats were screened using the Feline Temperament Profile to identify a calm temperament. Surveys measured children's social skills and anxiety and parent/child cat bonding. RESULTS: Our study (N = 11) found cat adoption was associated with greater Empathy and less Separation Anxiety for children with ASD, along with fewer problem behaviors including Externalizing, Bullying and Hyperactivity/Inattention. Parents and children reported strong bonds to the cats. CONCLUSION: This exploratory study found introduction of a cat into the home may have a positive impact on children with ASD and their parents. Based on this intial finding, future studies with larger sample sizes are recommended. PRACTICE IMPLICATIONS: If parents of children with ASD are considering cat adoption, health care providers might consider recommending adoption of a cat screened for calm temperament.

Risks of phase I research with healthy participants: A systematic review.

BACKGROUND/AIMS: Tragedies suggest that phase I trials in healthy participants may be highly risky. This possibility raises concern that phase I trials may exploit healthy participants to develop new therapies, making the translation of scientific discoveries ethically worrisome. Yet, few systematic data evaluate this concern. This article systematically reviews the risks of published phase I trials in healthy participants and evaluates trial features associated with increased risks. METHODS: Data on adverse events and trial characteristics were extracted from all phase I trials published in PubMed, Embase, Cochrane, Scopus, and PsycINFO (1 January 2008-1 October 2012). Inclusion criteria were phase I studies that enrolled healthy participants of any age, provided quantitative adverse event data, and documented the number of participants enrolled. Exclusion criteria included (1) adverse event data not in English, (2) a "challenge" study in which participants were administered a pathogen, and (3) no quantitative information about serious adverse events. Data on the incidence of adverse events, duration of adverse event monitoring, trial agent tested, participant demographics, and trial location were extracted. RESULTS: In 475 trials enrolling 27,185 participants, there was a median of zero serious adverse events (interquartile range = 0-0) and a median of zero severe adverse events (interquartile range = 0-0) per 1000 treatment group participants/day of monitoring. The rate of mild and moderate adverse events was a median of 1147.19 per 1000 participants (interquartile range = 651.52-1730.9) and 46.07 per 1000 participants/adverse event monitoring day (interquartile range = 17.80-77.19). CONCLUSION: We conclude that phase I trials do cause mild and moderate harms but pose low risks of severe harm. To ensure that this conclusion also applies to unpublished trials, it is important to increase trial transparency.

Simultaneous MRI of lung structure and perfusion in a single breathhold.

PURPOSE: To develop and demonstrate a breathheld 3D radial ultrashort echo time (UTE) acquisition to visualize co-registered lung perfusion and vascular structure. MATERIALS AND METHODS: Nine healthy dogs were scanned twice at 3 Tesla (T). Contrast-enhanced pulmonary perfusion scans were acquired with a temporally interleaved three-dimensional (3D) radial UTE (TE = 0.08 ms) sequence in a breathhold (1 s time frames over a 33 s breathhold). The 3D breathheld volume was reconstructed into time-resolved perfusion datasets, and a composite vascular structure dataset. For structural comparison, a 5 min respiratory-gated 3D radial UTE scan was acquired. Data were analyzed by quantitative metrics and radiologist scoring. RESULTS: Appropriate time-course of contrast was seen in all subjects. Right ventricle to aorta transit times were 7.4 ± 2.0 s. Relative lung enhancement was a factor of 8.4 ± 1.5. Radiologist scoring showed similarly excellent visualization of the pulmonary arteries to the subsegmental level in breathheld (94% of cases) and respiratory-gated (100% of cases) acquisitions (P = 0.33) despite the aggressive under sampling in the breathheld scan. Similarly, differentiation of lung tissue and airways was achieved by both acquisition methods. CONCLUSION: A time-resolved 3D radial UTE sequence for simultaneous imaging of pulmonary perfusion and co-registered vascular structure is feasible.

A review of ethical issues in dementia.

Dementia raises many ethical issues. The present review, taking note of the fact that the stages of dementia raise distinct ethical issues, focuses on three issues associated with stages of dementia's progression: (1) how the emergence of preclinical and asymptomatic but at-risk categories for dementia creates complex questions about preventive measures, risk disclosure, and protection from stigma and discrimination; (2) how despite efforts at dementia prevention, important research continues to investigate ways to alleviate clinical dementia's symptoms, and requires additional human subjects protections to ethically enroll persons with dementia; and (3) how in spite of research and prevention efforts, persons continue to need to live with dementia. This review highlights two major themes. First is how expanding the boundaries of dementias such as Alzheimer's to include asymptomatic but at-risk persons generate new ethical questions. One promising way to address these questions is to take an integrated approach to dementia ethics, which can include incorporating ethics-related data collection into the design of a dementia research study itself. Second is the interdisciplinary nature of ethical questions related to dementia, from health policy questions about insurance coverage for long-term care to political questions about voting, driving, and other civic rights and privileges to economic questions about balancing an employer's right to a safe and productive workforce with an employee's rights to avoid discrimination on the basis of their dementia risk. The review highlights these themes and emerging ethical issues in dementia.

Challenging the Sanctity of Donorism: Patient Tissue Providers as Payment-Worthy Contributors.

Many research projects rely on human biological materials and some of these projects generate revenue. Recently, it has been argued that investigators have a moral claim to share in the revenue generated by these projects, whereas persons who provide the biological material have no such claim (Truog, Kesselheim, and Joffe 2012). In this paper, we critically analyze this view and offer a positive proposal for why tissue providers have a moral claim to benefit. Focusing on payment as a form of benefit, we argue that research is a joint project and propose a contribution principle for paying participants in those joint projects. We distinguish between contributions that shape a project's revenue generating properties, grounding a claim to payment, and contributions that fail to ground such a claim. We conclude, contrary to existing arguments and practices, that some tissue providers have a moral claim to payment beyond compensation for risk and burden. This conclusion suggests that investigators, institutions, and sponsors should reconsider the fairness of their current practices.

Assessment of respiration-induced displacement of canine abdominal organs in dorsal and ventral recumbency using multislice computed tomography.

Respiratory-induced organ displacement during image acquisition can produce motion artifacts and variation in spatial localization of an organ in diagnostic computed tomography (CT) examinations. The purpose of this prospective study was to quantify respiratory-induced abdominal organ displacement in dorsal and ventral recumbency using five normal dogs. All dogs underwent CT examinations using 64 multidetector row CT (64-MDCT). A "3-dimensional (3D) apneic CT exam" of the abdomen was acquired followed by a "4-dimensional (4D) ventilated CT exam." The liver, pancreas, both kidneys, both medial iliac lymph nodes, and urinary bladder were delineated on the 3D-apneic examination and the organ outlines were compared to the maximum alteration in organ position in the 4D-ventilated examination. Displacement was measured in dorsal-to-ventral (DV), right-to-left (RL), and cranial-to-caudal (CC) directions. Respiratory-induced displacement of canine abdominal organs was not predictable and showed large variability in the three directions evaluated. For most canine abdominal organs, dorsal recumbency provided overall the least amount of displacement among all directions evaluated except for liver and urinary bladder. For liver, a large variability was found for all directions and a statistically significant difference was found only in the RL direction with ventral recumbency exhibiting less displacement (P = 0.0099). For the urinary bladder, ventral recumbency also provided less displacement but this was statistically significant only in the RL direction (P < 0.0001). Findings from this study indicated that dorsal recumbency may be preferred for minimizing respiratory motion artifacts in whole abdomen studies, but ventral recumbency may be preferred for liver and urinary bladder studies when respiration cannot be controlled.

Effects of two different anesthetic protocols on 64-MDCT coronary angiography in dogs.

Heart rate is a major factor influencing diagnostic image quality in computed tomographic coronary artery angiography (MDCT-CA), with an ideal heart rate of 60-65 beats/min in humans. The purpose of this prospective study was to compare effects of two different clinically applicable anesthetic protocols on cardiovascular parameters and 64-MDCT-CA quality in 10 healthy dogs. Scan protocols and bolus volumes were standardized. Image evaluations were performed in random order by a board-certified veterinary radiologist who was unaware of anesthetic protocols used. Heart rate during image acquisition did not differ between protocols (P = 1), with 80.6 ± 7.5 bpm for protocol A and 79.2 ± 14.2 bpm for protocol B. Mean blood pressure was significantly higher (P > 0.05) using protocol B (protocol A 62.9 ± 9.1 vs. protocol B 72.4 ± 15.9 mmHg). The R-R intervals allowing for best depiction of individual coronary artery segments were found in the end diastolic period and varied between the 70% and 95% interval. Diagnostic quality was rated excellent, good, and moderate in the majority of the segments evaluated, with higher scores given for more proximal segments and lower for more distal segments, respectively. Blur was the most commonly observed artifact and mainly affected the distal segments. No significant differences were identified between the two protocols for optimal reconstruction interval, diagnostic quality and measured length individual segments, or proximal diameter of the coronary arteries (P = 1). Findings indicated that, when used with a standardized bolus volume, both of these anesthetic protocols yielded diagnostic quality coronary 64-MDCT-CA exams in healthy dogs.

Effects of two different anesthetic protocols on cardiac flow measured by two dimensional phase contrast magnetic resonance imaging.

Companion animals are routinely anesthetized or heavily sedated for cardiac MRI studies, however effects of varying anesthetic protocols on cardiac function measurements are incompletely understood. The purpose of this prospective study was to compare effects of two anesthetic protocols (Protocol A: Midazolam, fentanyl; Protocol B: Dexmedetomidine) on quantitative and qualitative blood flow values measured through the aortic, pulmonic, mitral, and tricuspid valves using two-dimensional phase contrast magnetic resonance imaging (2D PC MRI) in healthy dogs. Mean flow per heartbeat values through the pulmonary artery (Qp) and aorta (Qs) were compared to right and left ventricular stroke volumes (RVSV, LVSV) measured using a reference standard of 2D Cine balanced steady-state free precession MRI. Pulmonary to systemic flow ratio (Qp/Qs) was also calculated. Differences in flow and Qp/Qs values generated using 2D PC MRI did not differ between the two anesthetic protocols (P = 1). Mean differences between Qp and RVSV were 3.82 ml/beat (95% limits of agreement: 3.62, -11.26) and 1.9 ml/beat (-7.86, 11.66) for anesthesia protocols A and B, respectively. Mean differences between Qs and LVSV were 1.65 ml/beat (-5.04, 8.34) and 0.03 ml/beat (-4.65, 4.72) for anesthesia protocols A and B, respectively. Mild tricuspid or mitral reflux was seen in 2/10 dogs using 2D PC MRI. No aortic or pulmonic insufficiency was observed. Findings from the current study indicated that these two anesthetic protocols yield similar functional measures of cardiac blood flow using 2D PC MRI in healthy dogs. Future studies in clinically affected patients are needed.

QUANTITATIVE PLANAR AND VOLUMETRIC CARDIAC MEASUREMENTS USING 64 MDCT AND 3T MRI VS. STANDARD 2D AND M-MODE ECHOCARDIOGRAPHY: DOES ANESTHETIC PROTOCOL MATTER?

Cross-sectional imaging of the heart utilizing computed tomography and magnetic resonance imaging (MRI) has been shown to be superior for the evaluation of cardiac morphology and systolic function in humans compared to echocardiography. The purpose of this prospective study was to test the effects of two different anesthetic protocols on cardiac measurements in 10 healthy beagle dogs using 64-multidetector row computed tomographic angiography (64-MDCTA), 3T magnetic resonance (MRI) and standard awake echocardiography. Both anesthetic protocols used propofol for induction and isoflourane for anesthetic maintenance. In addition, protocol A used midazolam/fentanyl and protocol B used dexmedetomedine as premedication and constant rate infusion during the procedure. Significant elevations in systolic and mean blood pressure were present when using protocol B. There was overall good agreement between the variables of cardiac size and systolic function generated from the MDCTA and MRI exams and no significant difference was found when comparing the variables acquired using either anesthetic protocol within each modality. Systolic function variables generated using 64-MDCTA and 3T MRI were only able to predict the left ventricular end diastolic volume as measured during awake echocardiogram when using protocol B and 64-MDCTA. For all other systolic function variables, prediction of awake echocardiographic results was not possible (P = 1). Planar variables acquired using MDCTA or MRI did not allow prediction of the corresponding measurements generated using echocardiography in the awake patients (P = 1). Future studies are needed to validate this approach in a more varied population and clinically affected dogs.

Maropitant prevented vomiting but not gastroesophageal reflux in anesthetized dogs premedicated with acepromazine-hydromorphone.

OBJECTIVE: To evaluate the efficacy of maropitant for prevention of vomiting and gastroesophageal reflux (GER) in dogs following acepromazine-hydromorphone premedication and inhalation anesthesia. STUDY DESIGN: Randomized, blinded, prospective clinical study. ANIMALS: Twenty-six dogs admitted for elective soft tissue or orthopedic procedures that were 3.1 ±3.1 years of age and weighed 20.5 ± 11.4 kg. METHODS: Dogs were randomly assigned to one of two groups: Group M received maropitant (1.0 mg kg(-1) ) and Group S received 0.9% saline (0.1 mL kg(-1) ) intravenously 45-60 minutes before premedication with hydromorphone (0.1 mg kg(-1) ) and acepromazine (0.03 mg kg(-1) ) intramuscularly. An observer blinded to treatment documented any retching or vomiting for 20 minutes before induction with propofol (2-6 mg kg(-1) ) and inhalation anesthesia. A pH probe inserted into the distal esophagus was used to detect GER. RESULTS: None of the dogs in Group M retched or vomited (0/13), 6/13 (46%) in Group S were observed to retch or vomit, and the difference between groups was significant (p = 0.015). There were no differences between groups in the number of dogs with GER (Group M: 4/13, Group S: 6/13 dogs) or the number of reflux events. Esophageal pH at the end of anesthesia was significantly lower in both M and S groups in dogs with GER versus dogs without GER (p = 0.004 and 0.011, respectively). Only dogs with GER in Group S had significantly lower pH at the end compared to the beginning of anesthesia (p = 0.004). CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous maropitant prevented retching and vomiting associated with acepromazine-hydromorphone premedication. Maropitant did not prevent the occurrence of GER. Fewer dogs in Group M developed GER but further study with a larger number of dogs is necessary to determine if there is a significant difference.

Physiologic and behavioral effects of long-acting subcutaneous and transdermal buprenorphine in rats.

OBJECTIVE: To investigate thermoregulation, thermal antinociception, food/kaolin intake, fecal output, and behavior following long-acting buprenorphine preparations in rats. ANIMALS: 8 adult male rats (Rattus norvegicus) were administered long-acting SC buprenorphine (SB; 0.65 mg/kg), transdermal buprenorphine (TB; 10 mg/kg), and controls in a randomized, cross-over design. METHODS: Body temperature, self-injury, sedation, food/kaolin intake, fecal output, and thermal withdrawal latencies were measured 1, 4, 8, 12, 24, 48, and 72 hours posttreatment. Data analysis was performed with mixed linear models. RESULTS: Self-injury was present between 1 and 12 hours and 4 and 12 hours following TB and SB, respectively; sedation was associated with TB at 12 to 24 hours. Withdrawal latencies were longer in both TB and SB groups than in the control group. Food intake decreased with time in all groups but was significantly lower 24 to 48 hours after TB and 24 to 72 hours after SB versus controls. Kaolin intake decreased from baseline 48 to 72 hours in the control group. Fecal output decreased from baseline 24 to 72 hours in all groups but was significantly lower than controls 24 hours following TB and 24 to 48 hours in SB. Body temperature increased from baseline at 1 hour, 1 to 12 hours, and 1 to 24 hours in the control, TB, and SB groups, respectively, and was significantly higher than the control group 1 to 72 hours following TB and 4 to 24 hours after SB. Transdermal buprenorphine and SB in normal rats produced antinociception, self-injurious behavior, hyperthermia, and decreased food/fecal output. CLINICAL RELEVANCE: Although these buprenorphine preparations may produce antinociception, untoward effects such as hyperthermia, self-injurious behavior, and reduced food intake/fecal output may be seen.

A randomized controlled trial evaluating the effects of nurse-led triage of 911 calls.

To better connect non-emergent 911 callers to appropriate care, Washington, DC, routed low-acuity callers to nurses. Nurses could provide non-emergent transportation to a health centre, recommend self-care or return callers to the traditional 911 system. Over about one year, 6,053 callers were randomized (1:1) to receive a business-as-usual response (ncontrol = 3,023) or further triage (ntreatment = 3,030). We report on seven of nine outcomes, which were pre-registered ( https://osf.io/xderw ). The proportion of calls resulting in an ambulance dispatch dropped from 97% to 56% (ß = -1.216 (-1.324, -1.108), P < 0.001), and those resulting in an ambulance transport dropped from 73% to 45% (ß = -3.376 (-3.615, -3.137), P < 0.001). Among those callers who were Medicaid beneficiaries, within 24 hours, the proportion of calls resulting in an emergency department visit for issues classified as non-emergent or primary care physician (PCP) treatable dropped from 29.5% to 25.1% (ß = -0.230 (-0.391, -0.069), P < 0.001), and the proportion resulting in the caller visiting a PCP rose from 2.5% to 8.2% (ß = 1.252 (0.889, 1.615), P < 0.001). Over the longer time span of six months, we failed to detect evidence of impacts on emergency department visits, PCP visits or Medicaid expenditures. From a safety perspective, 13 callers randomized to treatment were eventually diagnosed with a time-sensitive illness, all of whom were quickly triaged to an ambulance response. These short-term effects suggest that nurse-led triage of non-emergent calls can safely connect callers to more appropriate, timely care.

Development of a selective and scalable N1-indazole alkylation.

N1-Alkyl indazoles are a ubiquitous and privileged motif within medicinal chemistry, yet methods to selectively furnish N1-alkyl indazoles with simple alkyl side chains remain sparse. Herein, negative data from high-throughput experimentation (HTE) enabled a confident pivot of resource from continued optimisation to the development of an alternative reaction. This workflow culminated in a methodology for the synthesis of N1-alkyl indazoles. The procedure is highly selective for N1-alkylation, practical, and broad in scope, with no N2-alkyl products detected at completion. Mechanistic understandings were consistent with attributing the high selectivity to thermodynamic control. Additional data-driven process development led to this reaction being safely demonstrated on a 100 g scale, with potential for further scale up. This study highlights pragmatic principles followed to develop a necessitated methodology, suitable for large scale manufacture.

Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.

In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.

Genome-wide atlas of gene expression in the adult mouse brain.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

The efficacy of intracoelomic fospropofol in red-eared sliders (Trachemys scripta elegans).

Intravenous anesthetic delivery in reptiles can be challenging. Current injectable techniques have varied induction/recovery times and anesthetic quality. This study hypothesized that intracoelomic administration of a new anesthetic, fospropofol, in turtles would result in dose-dependent anesthesia and respiratory depression. A two-part prospective trial using adult red-eared slider turtles (Trachemys scripta elegans) weighing 764 +/- 17 g was conducted to determine an effective anesthetic dose and to evaluate the anesthetic quality, duration, and respiratory effects of an efficacious dose. In part 1, six turtles were randomly administered 25-mg/ kg (low-dose [LD]) and 50-mg/kg (high-dose [HD]) fospropofol in a crossover design. Respiratory rate, immobility, and muscle relaxation scores were evaluated for 180 min. In part 2, eight turtles were administered HD fospropofol. Immobility and muscle relaxation (front and hind limb) scores and time to endotracheal intubation/extubation were evaluated until scores returned to baseline. In part 1, the LD group had significantly lower immobility and muscle relaxation scores versus the HD group over time (both P < 0.05); scores were significantly elevated from baseline for 20-120 min and 15-180 min, respectively (all P < 0.05). Although not significantly different between groups (P > 0.05), respiratory rate was significantly decreased from baseline from 10 to 120 min (all P < 0.05). In part 2, HD fospropofol decreased respiratory rate from 21.5 +/- 2.9 breaths/min to 0.1 +/- 0.1 breaths/min, similar to the results in part 1. Maximal reductions in mobility and front and hind limb motor tone occurred at 39.0 +/- 4.1, 30.8 +/- 3.6, and 24.0 +/- 3.6 min, respectively. Intubation in 7/8 turtles occurred at 45.7 +/- 5.4 min and extubation at 147.0 +/- 23.2 min. However, 2/8 turtles showed prolonged anesthetic effects, requiring resuscitative efforts for recovery. Due to the unpredictable quality and duration of anesthesia with intracoelomic fospropofol, it should be used with caution for general anesthesia in red-eared sliders at the doses and administration route investigated.

Promoting one health: the University of Missouri Research Center for Human/Animal Interaction.

The University of Missouri's College of Veterinary Medicine is home to the Research Center for Human-Animal Interaction. This center uniquely addresses a growing area of research that focuses on how the human-animal bond impacts health in people and animals. This article highlights the One Health basis for the center, several research projects, and future goals for the center.