Exploring the Advantages and Challenges of MR-Guided Radiotherapy in Non-Small-Cell Lung Cancer: Who are the Optimal Candidates?

The landscape of lung radiotherapy (RT) has rapidly evolved over the past decade with modern RT and surgical techniques, systemic therapies, and expanding indications for RT. To date, 2 MRI-guided RT (MRgRT) units, 1 using a 0.35T magnet and 1 using a 1.5T magnet, are available for commercial use with more systems in the pipeline. MRgRT offers distinct advantages such as real-time target tracking, margin reduction, and on-table treatment adaptation, which may help overcome many of the common challenges associated with thoracic RT. Nonetheless, the use of MRI for image guidance and the current MRgRT units also have intrinsic limitations. In this review article, we will discuss clinical experiences to date, advantages, challenges, and future directions of MRgRT to the lung.

Multimodal pathways to joint attention in infants with a familial history of autism.

Joint attention (JA) is an early-developing behavior that allows caregivers and infants to share focus on an object. Deficits in JA, as measured through face-following pathways, are a defining feature of autism spectrum disorder (ASD) and are observable as early as 12 months of age in infants later diagnosed with ASD. However, recent evidence suggests that JA may be achieved through hand-following pathways by children with and without ASD. Development of JA through multimodal pathways has yet to be studied in infants with an increased likelihood of developing ASD. The current study investigated how 6-, 9- and 12-month-old infants with (FH+) and without (FH-) a family history of ASD engaged in JA. Parent-infant dyads played at home while we recorded the interaction over Zoom and later offline coded for hand movements and gaze. FH+ and FH- infants spent similar amounts of time in JA with their parents, but the cues available before JA were different. Parents of FH+ infants did more work to establish JA and used more face-following than hand-following pathways compared to parents of FH- infants, likely reflecting differences in infant motor or social behavior. These results suggest that early motor differences between FH+ and FH- infants may cascade into differences in social coordination.

Risk perception or hazard perception? Examining misperceptions of miners' personal exposures to noise.

While perceptions of risk have been examined in the workplace to understand safety behavior, hazard perception has been overlooked, particularly for chemical, physical, and biological agents. This study sought to establish the prevalence of one type of mismatch in hazard perception, - noise misperception - among miners, to examine whether different types of noisy environments (e.g., continuous, highly variable, etc.) alter workers' misperception of their noise exposures, and to evaluate whether noise misperception is associated with hearing protection device (HPD) use behavior. In this cross-sectional study across 10 surface mines in the USA, 135 normal-hearing participants were surveyed on their perceptions of exposure to noise at work and were monitored for three shifts, each with personal noise dosimetry, to examine which workers had a mismatch in perceived versus true noise exposure by 8-hr, time-weighted average, NIOSH exposure limits (TWANIOSH). Mixed effects logistic regression and probit Bayesian Kernel Machine Regression (BKMR) models examining on the odds of noise misperception associated with four different noise metrics (kurtosis, crest factor, variability, and number of peaks >135 dB) were used to determine which types of noisy environments may influence noise misperception. The relationship between noise misperception and odds of not wearing HPDs during a work shift was further examined. Our findings showed that nearly 1 in 3 workers underestimated their exposure to noise when their true exposure was in fact hazardous (TWANIOSH≥85 dBA) for at least one shift, and 6% misperceived hazardous exposures for all shifts. Work shifts with highly kurtotic noise distributions (>3) had 3.1 (95% CI: 1.1 to 8.4) times significantly higher odds of resulting in misperceived noise; no other noise metric was significantly associated with noise misperception. BKMR modeling provided further evidence that kurtosis dominates this relationship, with an IQR increase in kurtosis significantly associated with 1.68 (95% CI: 1.13 to 2.50) higher odds of noise misperception. Although not statistically significant, misperception of hazardous noise exposure was associated with 3.2 (95% CI: 0.8 to 12.5) times higher odds of not using earplugs during a work shift. Misperception of noise occurs in the workplace, and likely occurs for other physical, chemical, and biological exposures. This hazard misperception may influence risk perceptions and worker behavior and reduce the effectiveness of behavior-related training. Elimination, substitution, or engineering controls of exposures is the best way to prevent hazard misperceptions and exposure-related diseases.

The parasite intraerythrocytic cycle and human circadian cycle are coupled during malaria infection.

During infections with the malaria parasites Plasmodium vivax, patients exhibit rhythmic fevers every 48 h. These fever cycles correspond with the time the parasites take to traverse the intraerythrocytic cycle (IEC). In other Plasmodium species that infect either humans or mice, the IEC is likely guided by a parasite-intrinsic clock [Rijo-Ferreiraet al., Science 368, 746-753 (2020); Smith et al., Science 368, 754-759 (2020)], suggesting that intrinsic clock mechanisms may be a fundamental feature of malaria parasites. Moreover, because Plasmodium cycle times are multiples of 24 h, the IECs may be coordinated with the host circadian clock(s). Such coordination could explain the synchronization of the parasite population in the host and enable alignment of IEC and circadian cycle phases. We utilized an ex vivo culture of whole blood from patients infected with P. vivax to examine the dynamics of the host circadian transcriptome and the parasite IEC transcriptome. Transcriptome dynamics revealed that the phases of the host circadian cycle and the parasite IEC are correlated across multiple patients, showing that the cycles are phase coupled. In mouse model systems, host-parasite cycle coupling appears to provide a selective advantage for the parasite. Thus, understanding how host and parasite cycles are coupled in humans could enable antimalarial therapies that disrupt this coupling.

The role of adaptive planning in margin-reduced, MRI-guided stereotactic body radiotherapy to the prostate bed following radical prostatectomy: Post-hoc analysis of a phase II clinical trial.

BACKGROUND AND PURPOSE: We examined the interfractional variations of clinical target volumes (CTVs), planning target volumes (PTVs), and organs-at-risk (OARs) in patients receiving MRI-guided stereotactic body radiotherapy (SBRT) to the prostate bed and evaluated the potential role of adaptive planning. MATERIALS AND METHODS: 31 patients received 30-34 Gy in five fractions to the prostate bed on a phase II clinical trial. OARs, CTVs, and PTVs were retrospectively contoured on daily pretreatment MRIs (n = 155). Geometric comparisons were made between initial planning contours and daily pretreatment contours. Predicted treatment plans for each fraction were evaluated using the following constraints: CTV V95%>93%, PTV V95%>90%, bladder Dmax < 36.7 Gy, bladder V32.5 Gy < 35%, rectum Dmax < 36.7 Gy, rectum V27.5 Gy < 45%, rectum 32.5 Gy < 30%, and rectal wall V24Gy < 50%. Adaptive planning was simulated for all fractions that failed to meet these criteria. Plans were then re-evaluated. RESULTS: Median change in volume was 0.48% for CTV, -24.5% for bladder, and 6.95% for rectum. Median DSC was 0.89 for CTV, 0.79 for bladder, and 0.76 for rectum. 145/155 fractions (93.5%) met CTV V95%>93%. 75/155 fractions (48.4%) failed at least one OAR dose constraint. Overall, 83/155 fractions (53.5%) met criteria for adapting planning. This affected 24/31 patients (77.4%). Following adaptive planning, all fractions met CTV V95%>93% and PTV V95%>90% and 120/155 fractions (77.4%) met all OAR constraints. CONCLUSION: Due to significant interfractional variations in anatomy, a majority of fractions failed to meet both target volume and OAR constraints. However, adaptive planning was effective in overcoming these anatomic changes. Adaptive planning should be routinely considered in prostate bed SBRT.

Linking environmental injustices in Detroit, MI to institutional racial segregation through historical federal redlining.

OBJECTIVES: To identify the most pervasive environmental exposures driving environmental disparities today associated with historical redlining in Detroit. METHODS: We overlaid Detroit's 1939 Home Owners' Loan Corporation (HOLC) shapefile from the Mapping Inequality project onto the EPA EJScreen and the DOT National Transportation Noise maps to analyze differences in current demographic and environmental indicators between historically redlined (D-grade) and non-redlined neighborhoods using simple linear regression and a boosted classification tree algorithm. RESULTS: Historically redlined neighborhoods in Detroit experienced significantly higher environmental hazards than non-redlined neighborhoods in the form of 12.1% (95% CI: 7.2-17.1%) higher levels of diesel particulate matter (PM), 32.2% (95% CI: 3.3-69.3%) larger traffic volumes, and 65.7% (95% CI: 8.6-152.8%) higher exposure to hazardous road noise (LEQ(24h) >70 dBA). Historically redlined neighborhoods were situated near 1.7-times (95% CI: 1.4-2.1) more hazardous waste sites and twice as many (95% CI: 1.5-2.7) risk management plan (RMP) sites than non-redlined neighborhoods. The lifetime cancer risk from inhalation of air toxics was 4.4% (95% CI: 2.9-6.6%) higher in historically redlined communities, and the risk of adverse respiratory health outcomes from air toxics was 3.9% (95% CI: 2.1-5.6%) higher. All factors considered together, among the environmental hazards considered, the most pervasive hazards in historically redlined communities are proximity to RMP sites, hazardous road noise, diesel PM, and cancer risk from air pollution. CONCLUSIONS: Historically redlined neighborhoods may have a disproportionately higher risk of developing cancer and adverse respiratory health outcomes from air toxics. Policies targeting air and noise pollution from transportation sources, particularly from sources of diesel exhaust, in historically redlined neighborhoods may ameliorate some of the impacts of structural environmental racism from historical redlining in Detroit.

Evaluating Occupational Noise Exposure as a Contributor to Injury Risk among Miners.

OBJECTIVES: This study: (i) assessed the relationship between noise exposure and injury risk, comprehensively adjusting for individual factors, psychosocial stressors, and organizational influences; (ii) determined the relative importance of noise on injuries; (iii) estimated the lowest observed adverse effect level (LOAEL) of noise on injury risk to determine the threshold of noise considered hazardous to injuries; and (iv) quantified the fraction of injuries that could be attributed to hazardous noise exposure. METHODS: In this cross-sectional study at 10 US surface mine sites, traditional mixed effects, Poisson regression, and boosted regression tree (BRT) models were run on the number of reported work-related injuries in the last year. The LOAEL of noise on injuries was identified by estimating the percent increase in work-related injuries at different thresholds of noise exposure using a counterfactual estimator through the BRT model. A population attributable fraction (PAF) was quantified with this counterfactual estimator to predict reductions in injuries at the LOAEL. RESULTS: Among 18 predictors of work-related injuries, mine site, perceived job safety, age, and sleepiness were the most important predictors. Occupational noise exposure was the seventh most important predictor. The LOAEL of noise for work-related injuries was a full-shift exposure of 88 dBA. Exposure ≥88 dBA was attributed to 20.3% (95% CI: 11.2%, 29.3%) of reported work-related injuries in the last year among the participants. CONCLUSIONS: This study further supports hypotheses of a dose-response relationship between occupational noise exposure and work-related injuries, and suggests that exposures ≥88 dBA may increase injury risk in mining.

Assessing the impact of free-roaming dog population management through systems modelling.

Free-roaming dogs can present significant challenges to public health, wildlife conservation, and livestock production. Free-roaming dogs may also experience poor health and welfare. Dog population management is widely conducted to mitigate these issues. To ensure efficient use of resources, it is critical that effective, cost-efficient, and high-welfare strategies are identified. The dog population comprises distinct subpopulations characterised by their restriction status and level of ownership, but the assessment of dog population management often fails to consider the impact of the interaction between subpopulations on management success. We present a system dynamics model that incorporates an interactive and dynamic system of dog subpopulations. Methods incorporating both fertility control and responsible ownership interventions (leading to a reduction in abandonment and roaming of owned dogs, and an increase in shelter adoptions) have the greatest potential to reduce free-roaming dog population sizes over longer periods of time, whilst being cost-effective and improving overall welfare. We suggest that future management should be applied at high levels of coverage and should target all sources of population increase, such as abandonment, births, and owners of free-roaming dogs, to ensure effective and cost-efficient reduction in free-roaming dog numbers.

Beware the Grizzlyman: A comparison of job- and industry-based noise exposure estimates using manual coding and the NIOSH NIOCCS machine learning algorithm.

Recently, the National Institute for Occupational Safety and Health (NIOSH) released an updated version of the NIOSH Industry and Occupation Computerized Coding System (NIOCCS), which uses supervised machine learning to assign industry and occupational codes based on provided free-text information. However, no efforts have been made to externally verify the quality of assigned industry and job titles when the algorithm is provided with inputs of varying quality. This study sought to evaluate whether the NIOCCS algorithm was sufficiently robust with low-quality inputs and how variable quality could impact subsequent job estimated exposures in a large job-exposure matrix for noise (NoiseJEM). Using free-text industry and job descriptions from >700,000 noise measurements in the NoiseJEM, three files were created and input into NIOCCS: (1) N1, "raw" industries and job titles; (2) N2, "refined" industries and "raw" job titles; and (3) N3, "refined" industries and job titles. Standardized industry and occupation codes were output by NIOCCS. Descriptive statistics of performance metrics (e.g., misclassification/discordance of occupation codes) were evaluated for each input relative to the original NoiseJEM dataset (N0). Across major Standardized Occupational Classifications (SOC), total discordance rates for N1, N2, and N3 compared to N0 were 53.6%, 42.3%, and 5.0%, respectively. The impact of discordance on the major SOC group varied and included both over- and under-estimates of average noise exposure compared to N0. N2 had the most accurate noise exposure estimates (i.e., smallest bias) across major SOC groups compared to N1 and N3. Further refinement of job titles in N3 showed little improvement. Some variation in classification efficacy was seen over time, particularly prior to 1985. Machine learning algorithms can systematically and consistently classify data but are highly dependent on the quality and amount of input data. The greatest benefit for an end-user may come from cleaning industry information before applying this method for job classification. Our results highlight the need for standardized classification methods that remain constant over time.

Noise exposure and mental workload: Evaluating the role of multiple noise exposure metrics among surface miners in the US Midwest.

This study examined associations between metrics of noise exposure and mental workload. In this cross-sectional study, five occupational noise metrics computed from full-shift dosimetry were evaluated among surface mine workers in the US Midwest. Mental workload was evaluated using a modified, raw NASA-TLX and clustered with a k-means clustering algorithm. Mixed effects logistic regression and Bayesian Kernel Machine Regression (BKMR) was utilized for analysis. Average noise exposure, the difference between peak and mean noise exposure, and the number of peaks >135 dB were each strongly associated with mental workload, while the kurtosis and standard deviation of noise throughout a shift were not. An exposure-response relationship between average noise exposure and mental workload may exist, with elevated risk of high mental workload beginning at 80 dBA. These results suggest that high noise exposure may be an independent risk factor of high mental workload, and impulse events and the difference between the peak and mean noise exposure may have interactive effects with average noise exposure.

Monitoring SARS-CoV-2 in air and on surfaces and estimating infection risk in buildings and buses on a university campus.

BACKGROUND: Evidence is needed on the presence of SARS-CoV-2 in various types of environmental samples and on the estimated transmission risks in non-healthcare settings on campus. OBJECTIVES: The objective of this research was to collect data on SARS-CoV-2 viral load and to examine potential infection risks of people exposed to the virus in publicly accessible non-healthcare environments on a university campus. METHODS: Air and surface samples were collected using wetted wall cyclone bioaerosol samplers and swab kits, respectively, in a longitudinal environmental surveillance program from August 2020 until April 2021 on the University of Michigan Ann Arbor campus. Quantitative rRT-PCR with primers and probes targeting gene N1 were used for SARS-CoV-2 RNA quantification. The RNA concentrations were used to estimate the probability of infection by quantitative microbial risk assessment modeling and Monte-Carlo simulation. RESULTS: In total, 256 air samples and 517 surface samples were collected during the study period, among which positive rates were 1.6% and 1.4%, respectively. Point-biserial correlation showed that the total case number on campus was significantly higher in weeks with positive environmental samples than in non-positive weeks (p = 0.001). The estimated probability of infection was about 1 per 100 exposures to SARS-CoV-2-laden aerosols through inhalation and as high as 1 per 100,000 exposures from contacting contaminated surfaces in simulated scenarios. SIGNIFICANCE: Viral shedding was demonstrated by the detection of viral RNA in multiple air and surface samples on a university campus. The low overall positivity rate indicated that the risk of exposure to SARS-CoV-2 at monitored locations was low. Risk modeling results suggest that inhalation is the predominant route of exposure compared to surface contact, which emphasizes the importance of protecting individuals from airborne transmission of SARS-CoV-2 and potentially other respiratory infectious diseases. IMPACT: Given the reoccurring epidemics caused by highly infectious respiratory viruses in recent years, our manuscript reinforces the importance of monitoring environmental transmission by the simultaneous sampling and integration of multiple environmental surveillance matrices for modeling and risk assessment.

Retrospective assessment of the association between noise exposure and nonfatal and fatal injury rates among miners in the United States from 1983 to 2014.

BACKGROUND: Mining is a significant economic force in the United States but has historically had among the highest nonfatal injury rates across all industries. Several factors, including workplace hazards and psychosocial stressors, may increase injury and fatality risk. Mining is one of the noisiest industries; however, the association between injury risk and noise exposure has not been evaluated in this industry. In this ecological study, we assessed the association between noise exposure and nonfatal and fatal occupational injury rates among miners. METHODS: Federal US mining accident, injury, and illness data sets from 1983 to 2014 were combined with federal quarterly mining employment and production reports to quantify annual industry rates of nonfatal injuries and fatalities. An existing job-exposure matrix for occupational noise was used to estimate annual industry time-weighted average (TWA, dBA) exposures. Negative binomial models were used to assess relationships between noise, hearing conservation program (HCP) regulation changes in 2000, year, and mine type with incidence rates of injuries and fatalities. RESULTS: Noise, HCP regulation changes, and mine type were each independently associated with nonfatal injuries and fatalities. In multivariate analysis, each doubling (5 dB increase) of TWA was associated with 1.08 (95% confidence interval: 1.05, 1.11) and 1.48 (1.23, 1.78) times higher rate of nonfatal injuries and fatalities, respectively. HCP regulation changes were associated with 0.61 (0.54, 0.70) and 0.49 (0.34, 0.71) times lower nonfatal injury and fatality rates, respectively. CONCLUSION: Noise may be a significant independent risk factor for injuries and fatalities in mining.

In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [1-13 C]Pyruvate and Proton Density Fat Fraction in a Guinea Pig Model of Non-Alcoholic Fatty Liver Disease Development After Life-Long Western Diet Consumption.

BACKGROUND: Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. PURPOSE: To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. STUDY TYPE: Prospective. ANIMAL MODEL: Twenty-eight male guinea pigs weaned onto a control diet (N = 14) or WD (N = 14). FIELD STRENGTH/SEQUENCE: 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. ASSESSMENT: Median PDFF was calculated in the liver and hind limbs. [1-13 C]pyruvate dynamic MRS in the liver was quantified by the time-to-peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. STATISTICAL TESTS: Unpaired Student's t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. RESULTS: Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. DATA CONCLUSION: PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Hearing loss as a predictor for hearing protection attenuation among miners.

OBJECTIVE: This study investigated risk factors for poor earplug fit, with a focus on the association between hearing loss and personal attenuation ratings (PARs). METHODS: Earplug fit was assessed by obtaining PARs using a real ear at attenuation threshold (REAT) system. Hearing loss was assessed using the unoccluded hearing thresholds measured during the REAT testing and the results of a speech-in-noise test. Potential predictors of PARs were modelled using both simple and multiple linear regression. Hearing loss was the primary predictor of interest. RESULTS: Data were collected from 200 workers at ten above-ground mining sites in the Midwestern USA. Workers reported wearing their hearing protection on average 73.9% of the time in a high noise environment (mean 8-hour time-weighted average noise exposure 85.5 dBA, range 65-103 dBA). One-quarter (26.7%) of workers were found to have a hearing loss (hearing threshold ≥25 dB across 1-4 kHz), and 42% reported symptoms of tinnitus. Workers with a hearing loss had a significantly lower PAR than those without a hearing loss (ß=-5.1, SE=1.7). CONCLUSIONS: The results of the adjusted regression models suggest that workers with hearing loss achieved significantly lower PARs than those without hearing loss. This association between hearing loss and hearing protection devices (HPD) fit brings into focus the potential benefit of fit checks to be included in hearing conservation programmes. Workers found to have hearing loss should be prioritised for fit testing, as their hearing impairment may be associated with poor HPD fit.

The application of in utero magnetic resonance imaging in the study of the metabolic and cardiovascular consequences of the developmental origins of health and disease.

Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta's transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.

An intrinsic oscillator drives the blood stage cycle of the malaria parasite Plasmodium falciparum.

The blood stage of the infection of the malaria parasite Plasmodium falciparum exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, which triggers 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes or by a parasite-intrinsic oscillator. To distinguish between these hypotheses, we examine the P. falciparum cycle in an in vitro culture system and show that the parasite has molecular signatures associated with circadian and cell cycle oscillators. Each of the four strains examined has a different period, which indicates strain-intrinsic period control. Finally, we demonstrate that parasites have low cell-to-cell variance in cycle period, on par with a circadian oscillator. We conclude that an intrinsic oscillator maintains Plasmodium's rhythmic life cycle.

Optimizing SNR for multi-metabolite hyperpolarized carbon-13 MRI using a hybrid flip-angle scheme.

PURPOSE: To improve the SNR of hyperpolarized carbon-13 MRI of [1-13 C]pyruvate using a multispectral variable flip angle (msVFA) scheme in which the spectral profile and flip angle vary dynamically with time. METHODS: Each image acquisition in a time-resolved imaging experiment used a unique spectrally varying RF pulse shape for msVFA. Therefore, the flip angle for every acquisition was optimized for pyruvate and each of its metabolites to yield the highest SNR across the acquisition. Multispectral VFA was compared with a spectrally varying constant flip-angle excitation model through simulations and in vivo. A modified broadband chemical shift-encoded gradient-echo sequence was used for in vivo experiments on six pregnant guinea pigs. Regions of interest placed in the placentae, maternal liver, and maternal kidneys were used as areas for SNR measurement. RESULTS: In vivo experiments showed significant increases in SNR for msVFA relative to constant flip angle of up to 250% for multiple metabolites. CONCLUSION: Hyperpolarized carbon-13 imaging with msVFA excitation produces improved SNR for all metabolites in organs of interest.

Using extremal events to characterize noisy time series.

Experimental time series provide an informative window into the underlying dynamical system, and the timing of the extrema of a time series (or its derivative) contains information about its structure. However, the time series often contain significant measurement errors. We describe a method for characterizing a time series for any assumed level of measurement error [Formula: see text] by a sequence of intervals, each of which is guaranteed to contain an extremum for any function that [Formula: see text]-approximates the time series. Based on the merge tree of a continuous function, we define a new object called the normalized branch decomposition, which allows us to compute intervals for any level [Formula: see text]. We show that there is a well-defined total order on these intervals for a single time series, and that it is naturally extended to a partial order across a collection of time series comprising a dataset. We use the order of the extracted intervals in two applications. First, the partial order describing a single dataset can be used to pattern match against switching model output (Cummins et al. in SIAM J Appl Dyn Syst 17(2):1589-1616, 2018), which allows the rejection of a network model. Second, the comparison between graph distances of the partial orders of different datasets can be used to quantify similarity between biological replicates.

Ultrasound-guided blocks for cardiovascular surgery: which block for which patient?

PURPOSE OF REVIEW: Regional anesthesia blocks may benefit patients undergoing cardiovascular surgery. This review coincides with the evolution of ultrasound-guided fascial plane blocks, societal concerns regarding opioid misuse and changing expectations regarding surgical recovery. RECENT FINDINGS: Paravertebral block and thoracic epidural analgesia have comparable postoperative analgesic profiles following thoracotomy; however, the former has a more favorable complication profile. Limited trials have compared these modalities in cardiac surgery. The mechanism of action of continuous paravertebral blockade may be systemic. Bilateral continuous paravertebral (and other continuous peripheral nerve blocks) should be used with caution in adult patients having cardiac surgery because of the risk of systemic local anesthetic toxicity and bleeding. Novel ultrasound-guided blocks: erector spinae, serratus anterior, pectoral, transversus thoracic muscle and pecto-intercostal fascial plane blocks potentially reduce postoperative opioid requirements; however, they require further investigation before their routine use can be recommended in adult cardiovascular surgical practice. The mechanism of action of erector spinae block is not fully elucidated. SUMMARY: Ultrasound-guided fascial plane blocks may reduce postoperative opioid requirements. Investigation into the safety and efficacy of bilateral continuous ultrasound-guided blockade for cardiac surgery is required. Trial protocols should be embedded into enhanced recovery after surgery programs. Patient-reported and long-term outcomes are recommended.

The Effectiveness of Dog Population Management: A Systematic Review.

The worldwide population of domestic dogs is estimated at approximately 700 million, with around 75% classified as "free-roaming". Where free-roaming dogs exist in high densities, there are significant implications for public health, animal welfare, and wildlife. Approaches to manage dog populations include culling, fertility control, and sheltering. Understanding the effectiveness of each of these interventions is important in guiding future dog population management. We present the results of a systematic review of published studies investigating dog population management, to assess: (1) where and when studies were carried out; (2) what population management methods were used; and (3) what was the effect of the method. We evaluated the reporting quality of the published studies for strength of evidence assessment. The systematic review resulted in a corpus of 39 papers from 15 countries, reporting a wide disparity of approaches and measures of effect. We synthesised the management methods and reported effects. Fertility control was most investigated and had the greatest reported effect on dog population size. Reporting quality was low for power calculations (11%), sample size calculations (11%), and the use of control populations (17%). We provide recommendations for future studies to use common metrics and improve reporting quality, study design, and modelling approaches in order to allow better assessment of the true impact of dog population management.