Determining the effect of cardiac blood volume on accuracy of uptake rate constants by simulation.

Objective. There is great interest in better understanding coronary microvascular disease using mouse models. Typical quantification requires dynamic imaging to estimate the rate constantK1of the tracer moving from the blood into the myocardium. In addition toK1, it is also desirable to determine blood volume fractionV, which if known allows for more accurate fitting ofK1. Our previously published kinetic modeling software did not consider the effect ofV. To ensure a better fit of experimental data to the model for myocardialµSPECT imaging, in this work we updated our kinetic modeling software to include a blood volume fractionV, which adds a fraction of the arterial activity concentration into the tissue concentration.Approach. The tissue and blood time-activity curves (TACs) used for fit input were generated using ideal equations with known values in MATLAB. This allowed post-fit results to be compared to known values to determine fit errors. Parameters that were varied in generating the TACs included blood volume fraction (0, 0.05, 0.1, 0.2 and 0.3),K1(0.5, 1.5, 2.5 ml min-1g-1), frame length (1, 2, 5, 10, 15, 20 s), FWHM of the input Gaussian (10, 20, 40 s), and time of the injection peak relative to frame duration. Blood volume-fraction results have low error when blood volume is lowest, but results worsen as frame length andK1increase.Main results. We demonstrated that blood volume can be accurately determined, and also show how fit accuracy varies across TACs with different input properties.Significance. This information allows for robust use of the fitting algorithm and aids in understanding fit performance when used in animal studies.

The Practical Haplotype Graph, a platform for storing and using pangenomes for imputation.

MOTIVATION: Pangenomes provide novel insights for population and quantitative genetics, genomics and breeding not available from studying a single reference genome. Instead, a species is better represented by a pangenome or collection of genomes. Unfortunately, managing and using pangenomes for genomically diverse species is computationally and practically challenging. We developed a trellis graph representation anchored to the reference genome that represents most pangenomes well and can be used to impute complete genomes from low density sequence or variant data. RESULTS: The Practical Haplotype Graph (PHG) is a pangenome pipeline, database (PostGRES & SQLite), data model (Java, Kotlin or R) and Breeding API (BrAPI) web service. The PHG has already been able to accurately represent diversity in four major crops including maize, one of the most genomically diverse species, with up to 1000-fold data compression. Using simulated data, we show that, at even 0.1× coverage, with appropriate reads and sequence alignment, imputation results in extremely accurate haplotype reconstruction. The PHG is a platform and environment for the understanding and application of genomic diversity. AVAILABILITY AND IMPLEMENTATION: All resources listed here are freely available. The PHG Docker used to generate the simulation results is https://hub.docker.com/ as maizegenetics/phg:0.0.27. PHG source code is at https://bitbucket.org/bucklerlab/practicalhaplotypegraph/src/master/. The code used for the analysis of simulated data is at https://bitbucket.org/bucklerlab/phg-manuscript/src/master/. The PHG database of NAM parent haplotypes is in the CyVerse data store (https://de.cyverse.org/de/) and named/iplant/home/shared/panzea/panGenome/PHG_db_maize/phg_v5Assemblies_20200608.db. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Development and feasibility of quantitative dynamic cardiac imaging for mice using µSPECT.

BACKGROUND: Despite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function. METHODS: We used 99mTc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT+ system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used 99mTc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function. RESULTS: The recovery coefficients for myocardial tissue (RT) and left ventricular arterial blood (RA) were 0.81 ± 0.16 and 1.07 ± 0.12, respectively. The assumption RT = 1 - FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min-1. Constraints on the extraction fraction curve for 99mTc-sestamibi in mice for best-fit Renkin-Crone parameters were α = 0.99 and ß = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 ± 3.3% under hyperemic conditions. CONCLUSIONS: We have developed a framework for measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function.

Effect of pinhole shape on projection resolution.

We are designing a dual-resolution pre-clinical SPECT system based on square-pinhole apertures for use in applications with a small field-of-view (FOV), such as cardiac imaging of mice. Square pinholes allow for increased sensitivity due to more efficient projection tiling on the detector compared to circular pinholes. Aperture fabrication techniques cannot produce a perfect square, giving the square pinholes some amount of roundedness at the corners. This work investigates how this roundedness affects the physical properties of projection images in terms of spatial resolution. Different pinhole full-acceptance angles and roundedness values were simulated. To facilitate a fair comparison, properties of the non-square pinholes were manipulated to yield pinholes with approximately the same sensitivity (to within 0.1%) and FOV (to within 0.5%) as those of the square pinholes, subsequently referred to as matched apertures. The aperture size (flat-to-flat edge length) of each non-square aperture was increased until its sensitivity was approximately equal to that of the square pinhole. Next, the full acceptance angle was increased until the FOV of each non-square aperture was approximately equivalent to that of the square pinhole. Sensitivity was calculated to include both the geometric and penetrative sensitivity of a point source, as well as the packing faction of the multi-pinhole collimator. Using the sensitivity-matched and FOV-matched apertures, spatial resolution was estimated. For the 0.3 mm, 0.5 mm, and 1 mm edge-length square apertures studied, the full-width at half-maximum widened as pinhole shape changed from square to circle, while full-width tenth-maximum showed little change. These results indicate that a perfect square pinhole shape is more desirable than a rounded-square pinhole with regard to spatial resolution when sensitivity and FOV-matched pinholes are compared.

Tract-based spatial statistics of diffusion tensor imaging in adults with dyslexia.

BACKGROUND AND PURPOSE: Diffusion tensor imaging is a tool that can be used to study white matter microstructure in dyslexia. We tested the hypothesis that dyslexics have a white matter structural change (as measured by directional diffusion of water, which can be affected by disruption in white matter tracts) between brain regions that previous functional connectivity studies showed were associated with phonologic processing. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) scans were acquired from 7 healthy adult normal readers and from 14 adults with dyslexia on a 1.5T scanner. Voxelwise statistical analysis of the fractional anisotropy data were carried out by using Tract-Based Spatial Statistics to compare dyslexic subjects versus control subjects in white matter tracts. RESULTS: Significant group difference map clusters (comparing adults with and without dyslexia) occurred in specific bilateral white matter tracts within the frontal lobe, temporal lobe, occipital lobe, and parietal lobe. CONCLUSION: The DTI fractional anisotropy results in the bilateral white matter showing higher fractional anisotropy in adult control subjects compared with adults with dyslexia (relating to white matter fiber tract integrity) are consistent with our previous functional connectivity results from seed points in the bilateral inferior frontal gyrus.

Ecological genomics: understanding gene and genome function in the natural environment.

The field of ecological genomics seeks to understand the genetic mechanisms underlying responses of organisms to their natural environments. This is being achieved through the application of functional genomic approaches to identify and characterize genes with ecological and evolutionary relevance. By its very nature, ecological genomics is an interdisciplinary field. In this review, we consider the significance of this new area of study from both an ecological and genomic perspective using examples from the recent literature. We submit that by considering more fully an ecological context, researchers may gain additional insights into the underlying genetic basis of ecologically relevant phenotypic variation. Likewise, genomic approaches are beginning to offer new insights into higher-level biological phenomena that previously occupied the realm of ecological investigation only. We discuss various approaches that are likely to be useful in ecological genomic studies and offer thoughts on where this field is headed in the future.

Sustained stabilization of the resistive-wall mode by plasma rotation in the DIII-D tokamak.

Values of the normalized plasma pressure up to twice the free-boundary stability limit predicted by ideal magnetohydrodynamic (MHD) theory have been sustained in the DIII-D tokamak. Long-wavelength modes are stabilized by the resistive wall and rapid plasma toroidal rotation. High rotation speed is maintained by minimization of nonaxisymmetric magnetic fields, overcoming a long-standing impediment [E. J. Strait, Phys. Rev. Lett. 74, 2483 (1995)]]. The ideal-MHD pressure limit calculated with an ideal wall is observed as the operational limit to the normalized plasma pressure.

Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary disease.

BACKGROUND: The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease (COPD) during a high intensity outpatient cycle exercise programme were examined. METHODS: Nineteen patients (17 men) with severe COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 27 (7)% predicted) underwent a 6 week supervised outpatient cycle exercise programme. Ten patients were randomised to exercise with ventilatory assistance using proportional assist ventilation (PAV) and nine (two women) to exercise unaided. Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate (Wpeak) followed by a constant work rate (CWR) test at 70% of Wpeak achieved in the baseline incremental test. Minute ventilation (VE), heart rate, and arterialised venous plasma lactate concentration [La(+)] were measured before and after each test. RESULTS: Mean training intensity (Wt/Wpeak) at 6 weeks was 15.2% (95% CI 3.2 to 27.1) higher in the group that used ventilatory assistance (p=0.016). Peak work rate after training was 18.4% (95% CI 6.4 to 30.5) higher (p=0.005) in the assisted group (p=0.09). [La(+)] at an identical workload after training was reduced by 30% (95% CI 16 to 44) in the assisted group (p=0.002 compared with baseline) and by 11% (95% CI -7 to 31) (p=0.08 compared with baseline) in the unassisted group (mean difference 18.4% (95% CI 3.3 to 40), p=0.09). A significant inverse relationship was found between reduction in plasma lactate concentration (DeltaL) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training (r=-0.7, p=0.0006). CONCLUSIONS: PAV enables a higher intensity of training in patients with severe COPD, leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation.

Inspiratory muscle maximum relaxation rate measured from submaximal sniff nasal pressure in patients with severe COPD.

BACKGROUND: Slowing of the inspiratory muscle maximum relaxation rate (MRR) is a useful index of severe inspiratory muscle loading and potential fatigue and has been measured from the oesophageal pressure during sniffs in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate whether it is possible to measure MRR and detect slowing using sniff nasal pressure in patients with COPD and to investigate the relationship between sniff oesophageal and sniff nasal MRR. METHODS: Eight patients with severe COPD (mean FEV1 0.7 l; 26% predicted) were studied. Each subject performed submaximal sniff manoeuvres before and after walking to a state of severe dyspnoea on a treadmill. Oesophageal and gastric pressures were measured using balloon tipped catheters and nasal pressure was measured using an individually modelled nasal cast. MRR (% pressure fall/10 ms) was determined for each sniff and any change following exercise was reported as percentage of baseline to allow comparison of sniff nasal and oesophageal MRR. RESULTS: At rest the mean (SE) sniff Poes MRR was 7.1 (0.3) and the mean Pnasal MRR was 8.6 (0.1). At 1 minute following exercise there was a mean decrease in sniff Poes MRR of 33.7% (range 20.7-53.4%) and a mean decrease in sniff Pnasal MRR of 28.2% (range 8.1-52.8%). The degree of slowing and time course of recovery was similar, with both returning to baseline values within 5-10 minutes. A separate analysis of the sniff pressures using only the nasal pressure traces demonstrated a similar pattern of slowing and recovery. CONCLUSIONS: It is possible to detect slowing of the inspiratory muscles non-invasively using sniff nasal pressures in patients with COPD. This could be a useful technique with which to measure severe and potentially fatiguing inspiratory muscle loading, both in clinical settings and during exercise studies.

The community/privacy trade-off in supportive housing: consumer/survivor preferences.

Supportive housing for psychiatric consumers/survivors can range in form from dispersed apartments to group homes. This research asked: What form is more supportive, apartments or housing with common spaces? Is it privacy and normalcy or community and peer support that promote well-being? The literature is divided. This study convened a charrette for supportive housing residents to express their views. Some 20 supportive housing residents formed two teams, with one team producing a housing design based on the principle of privacy and the other team producing one based on the principle of community. Despite their differing terms of reference, the teams developed similar designs. The results reinforced the importance of both private and common spaces in supportive housing.

Outcomes of a leadership intervention for a metropolitan fire department.

Poor leadership can contribute to job dissatisfaction and employees' "burnout." Perceived lack of leadership skills is also a source of stress for supervisors. This study evaluated the efficacy of a brief multicomponent leadership intervention provided for fire service supervisors in an urban fire department. Ratings by 51 line firefighters and 8 first-line supervisors documented improvements in their immediate supervisors' performance at 3 mo. postintervention. Self-reports by line firefighters also showed improvements in perceptions of their ability to attain career goals, which were sustained at 9 mo. postintervention. There were also improvements on certain stress related symptoms indices reported by the sample of firefighter supervisors at both the 3-mo. and 9-mo. follow-ups. No significant changes on any of these measures, obtained at comparable time points, were observed in a (nonequivalent) control sample of firefighters and their first-line supervisors in an "untreated" urban fire department.

The effects of early exposure of cellulitis-associated Escherichia coli in 1-day-old broiler chickens.

Two experiments were performed to test the effect of various field strains of Escherichia coli of cellulitis origin. In the first experiment, 1-day-old broiler chicks were challenged with one of two E. coli field strains using inoculation routes including oral gavage, swabbing of the navel and subcutaneous injection. No cellulitis lesions were produced, although the birds experienced high levels of septicemia/toxemia, characteristic of colibacillosis. The birds that received the E. coli by subcutaneous injection experienced the highest rate of mortality, while those that were challenged by gavage and those that had their navels swabbed experienced lesser rates of mortality. Birds in the second experiment were challenged at 1 day of age with one of three field strains of cellulitis-origin E. coli administered alone or in combination (1:1), which were serially diluted prior to subcutaneous injection. No significant differences in body weight, mortality or cellulitis rates were associated with specific isolates given; however, significant differences were seen with mortality and cellulitis rates according to the dilution of bacteria given. A linear effect was also noted with body weight at 3 weeks, again correlating to the dilution of bacteria that the chicks received.

The influence of Escherichia coli strains from different sources and the age of broiler chickens on the development of cellulitis.

In two experiments, broilers were challenged with one of several field strains of Escherichia coli to determine whether the source of the E. coli and age of the bird at time of inoculation affected the development of cellulitis lesions. In the first experiment, birds inoculated at 52 days of age with E. coli of faecal, airsacculitis and cellulitis origin exhibited a cellulitis lesion incidence of 47.5, 25 and 77.5%, respectively. This study confirms earlier observations that E. coli strains isolated from cellulitis lesions express a higher propensity for producing these same lesions than other strains, including those associated with airsacculitis. In the second experiment, birds were inoculated at 4, 7, 10, 16, 28, and 52 days of age with an E. coli strain of cellulitis origin and necropsied 2 days post-infection. The resulting incidence of cellulitis ranged from 20% (day 7) to 95% (days 16 and 28), indicating that cellulitis can develop in any age of bird, although the lesions were frequently associated with other manifestations of colibacillosis (perihepatitis, pericarditis, airsacculitis) in birds challenged from 4 to 16 days of age.

Bone tumor dynamics: an orthopedic pathology perspective.

The diagnosis and classification of primary bone tumors remains as much a challenge today as it has for the last 80 plus years. Although pathology is invariably equated with the image of a diagnostic microscope, the vast majority of diagnoses are made grossly with the unaided eye, as are the tissue specimens selected for microscopic "confirmation." Radiologic studies, particularly plain radiographs, remain the gold standard in gross pathologic diagnosis of the skeleton. Today, confirmation and final classification continue as the pathologist's domain, but perhaps not for long, considering the evolving ancillary imaging techniques and progressive sophistication of magnetic resonance (MR) imaging. The bone tumor cases collected and compiled by Ernest Codman, M.D. during the second through fourth decades of this century formed the basis of the first tumor registry. The Codman Bone Sarcoma Registry demonstrated among other things the importance of radiographic/pathologic correlation, underscoring the reliability of a bone tumor's location, margin (host bone/tumor interface), periosteal reaction, and matrix patterns as an accurate guide to classification and likely future biologic behavior. "A General Theory of Bone Tumors," written by Lent C. Johnson nearly 50 years ago and published in the Bulletin of The New York Academy of Medicine (February 1953, second series, vol. 29, no. 2, pp. 164-171), provided a conceptual cellular approach to the understanding bone tumor dynamics reinforcing radiologic/pathologic correlation as a reliable diagnostic tool. At the time of Dr. Lent C. Johnson's death (1910-1998), he was literally working on an updated version of his original article, the latter of which is being reprinted as the core of this illustrated revision. Our continued experience with bone tumors over the past five decades has only served to validate, on a daily basis, the fundamental principles outlined in Johnson's original article. In like fashion, it is important to keep in mind that terminology and nomenclature has also evolved since 1953, despite a continued inability to achieve complete consensus.

PTSD among bereaved parents following the violent deaths of their 12- to 28-year-old children: a longitudinal prospective analysis.

This study examined the prevalence of posttraumatic stress disorder (PTSD) among parents bereaved by the violent deaths of their 12- to 28-year-old children. A community-based sample of 171 bereaved mothers and 90 fathers was recruited by a review of Medical Examiner records and followed for 2 years. Four important findings emerged: Both parents' gender and children's causes of death significantly affected the prevalence of PTSD symptoms. Twice as many mothers and fathers whose children were murdered met PTSD caseness (full diagnostic) criteria compared with accident and suicide bereavement. Symptoms in the reexperiencing domain were the most commonly reported. PTSD symptoms persisted over time, with 21% of the mothers and 14% of the fathers who provided longitudinal data still meeting caseness criteria 2 years after the deaths. Parents who met caseness criteria for PTSD, compared with those who did not, were significantly different on multiple study variables. Both theoretical and clinical implications for the findings are discussed.

Diaphragm electromyogram measured with unilateral magnetic stimulation.

The purpose of this study was to establish the phrenic nerve conduction time (PNCT) for magnetic stimulation and further assess the relatively new technique of anterior unilateral magnetic stimulation (UMS) of the phrenic nerves in evaluating the diaphragm electromyogram (EMG). An oesophageal electrode was used to record the diaphragm compound muscle action potential (CMAP) elicited by supramaximal percutaneous electrical phrenic nerve stimulation (ES) and UMS from eight normal subjects. The oesophageal electrode used for recording the CMAP was positioned at the level of the hiatus and 3 cm below. The diaphragm CMAP was also recorded from chest wall surface electrodes in five subjects. All of the phrenic nerves could be maximally stimulated with UMS. A clear plateau of the amplitude of the CMAP was achieved for the right and left phrenic nerves. The mean amplitudes of the CMAP recorded from the oesophageal electrode were, for the right side, 0.74+/-0.29 mV (mean+SD) for ES and 0.76+/-0.30 mV for UMS with maximal power output, and for the left side 0.88+/-0.33 mV for ES and 0.80+/-0.24 mV for UMS. PNCT measured by the oesophageal electrode with ES and UMS with maximal output were, for the right side, 7.0+/-0.8 ms and 6.9+/-0.8 ms, respectively, and for the left side 7.8+/-1.2 ms and 7.7+/-1.3 ms, respectively. However, the CMAP recorded from chest wall surface electrodes with UMS was unsuitable for the measurement of PNCT. The results suggest that unilateral magnetic stimulation of the phrenic nerves combined with an oesophageal electrode can be used to assess diaphragmatic electrical activity and measure the phrenic nerve conduction time.

Parents' health, health care utilization, and health behaviors following the violent deaths of their 12- to 28-year-old children: a prospective longitudinal analysis.

Health status, health care utilization, and health behaviors of parents bereaved by the violent deaths of their adolescent and young adult children were examined 4, 12, and 24 months later. Participants were 261 bereaved parents (171 mothers, 90 fathers). About 20% of the parents reported "poor" physical health during the early bereavement period compared with 16% of Americans the same age. Over time, mothers' health improved whereas fathers' health deteriorated. Fathers in poor health compared with fathers in good health are 15 times more likely to report emotional distress and 4.6 times more likely to report trauma symptoms. Mothers in poor health compared with mothers in good health are 11 times more likely to report emotional distress and 3 times more likely to report trauma symptoms. Mothers' reports of physician visits and medication use were higher than fathers', however, mothers' rates for both decreased significantly over time whereas fathers' rates remained constant. Over 70% of the mothers and nearly 60% of the fathers practiced 2 or more health protective behaviors over time--a finding significantly associated with fewer stress-related illnesses, days absent from work, and non-productivity at work. Implications for the findings are discussed.

Changes in parents' mental distress after the violent death of an adolescent or young adult child: a longitudinal prospective analysis.

This study examined changes in bereaved parents' mental distress following the violent deaths of their 12- to 28-year-old children. A community-based sample of 171 bereaved mothers and 90 fathers was recruited by a review of medical examiner records. Data were collected 4, 12, and 24 months post-death. Repeated measures analysis of variance showed significant reductions in 8 of 10 measures of mental distress among mothers and 4 of 10 for fathers, with the most change for both genders occurring between 4 and 12 months post-death. During the 2nd year of bereavement, mothers' symptoms continued to decline, whereas fathers, who started out with less distress than mothers, reported slight increases in 5 of 10 symptom domains. Nonetheless, 2 years after the deaths, mothers' mental distress scores were up to 5 times higher than those of "typical" U.S. women and fathers' scores were up to 4 times higher than "typical" U.S. men. Of the 7 intervening variables examined, higher scores on self-esteem and self-efficacy predicted lower distress for both mothers and fathers 4, 12, and 24 months post-death. Repressive coping was predictive of distress among fathers. It was concluded that violent death bereavement has sustained, distressing consequences on parents of children who die as a result of accidents, homicides, and suicide.

Diaphragm EMG measured by cervical magnetic and electrical phrenic nerve stimulation.

The purpose of the study was to compare electrical stimulation (ES) and cervical magnetic stimulation (CMS) of the phrenic nerves for the measurement of the diaphragm compound muscle action potential (CMAP) and phrenic nerve conduction time. A specially designed esophageal catheter with three pairs of electrodes was used, with control of electrode positioning in 10 normal subjects. Pair A and pair B were close to the diaphragm (pair A lower than pair B); pair C was positioned 10 cm above the diaphragm to detect the electromyogram from extradiaphragmatic muscles. Electromyograms were also recorded from upper and lower chest wall surface electrodes. The shape of the CMAP measured with CMS (CMS-CMAP) usually differed from that of the CMAP measured with ES (ES-CMAP). Moreover, the latency of the CMS-CMAP from pair B (5.3 +/- 0.4 ms) was significantly shorter than that from pair A (7.1 +/- 0.7 ms). The amplitude of the CMS-CMAP (1.00 +/- 0.15 mV) was much higher than that of ES-CMAP (0.26 +/- 0.15 mV) when recorded from pair C. Good-quality CMS-CMAPs could be recorded in some subjects from an electrode positioned very low in the esophagus. The differences between ES-CMAP and CMS-CMAP recorded either from esophageal or chest wall electrodes make CMS unreliable for the measurement of phrenic nerve conduction time.