Using Texture Analysis of Neck Computed Tomography Images to Differentiate Primary Hyperparathyroidism From Normal Controls.

OBJECTIVE: To investigate the utility of texture analysis in detecting osseous changes associated with hyperparathyroidism on neck CT examinations compared with control patients and to explore the best regions in the head and neck to evaluate changes in the trabecular architecture secondary to hyperparathyroidism. METHODS: Patients with hyperparathyroidism who underwent a 4D CT of the neck with contrast were included in this study. Age-matched control patients with no history of hyperparathyroidism who underwent a contrast-enhanced neck CT were also included. Mandibular condyles, bilateral mandibular bodies, the body of the C4 vertebra, the manubrium of the sternum, and bilateral clavicular heads were selected for analysis, and oval-shaped regions of interest were manually placed. These segmented areas were imported into an in-house developed texture analysis program, and 41 texture analysis features were extracted. A mixed linear regression model was used to compare differences in the texture analysis features contoured at each of the osseous structures between patients with hyperparathyroidism and age-matched control patients. RESULTS: A total of 30 patients with hyperparathyroidism and 30 age-matched control patients were included in this study. Statistically significant differences in texture features between patients with hyperparathyroidism and control patients in all 8 investigated osseous regions. The sternum showed the greatest number of texture features with statistically significant differences between these groups. CONCLUSIONS: Some CT texture features demonstrated statistically significant differences between patients with hyperparathyroidism and control patients. The results suggest that texture features may discriminate changes in the osseous architecture of the head and neck in patients with hyperparathyroidism.

Emergence and influence of sequence bias in evolutionarily malleable, mammalian tandem arrays.

BACKGROUND: The radiation of mammals at the extinction of the dinosaurs produced a plethora of new forms-as diverse as bats, dolphins, and elephants-in only 10-20 million years. Behind the scenes, adaptation to new niches is accompanied by extensive innovation in large families of genes that allow animals to contact the environment, including chemosensors, xenobiotic enzymes, and immune and barrier proteins. Genes in these "outward-looking" families are allelically diverse among humans and exhibit tissue-specific and sometimes stochastic expression. RESULTS: Here, we show that these tandem arrays of outward-looking genes occupy AT-biased isochores and comprise the "tissue-specific" gene class that lack CpG islands in their promoters. Models of mammalian genome evolution have not incorporated the sharply different functions and transcriptional patterns of genes in AT- versus GC-biased regions. To examine the relationship between gene family expansion, sequence content, and allelic diversity, we use population genetic data and comparative analysis. First, we find that AT bias can emerge during evolutionary expansion of gene families in cis. Second, human genes in AT-biased isochores or with GC-poor promoters experience relatively low rates of de novo point mutation today but are enriched for non-synonymous variants. Finally, we find that isochores containing gene clusters exhibit low rates of recombination. CONCLUSIONS: Our analyses suggest that tolerance of non-synonymous variation and low recombination are two forces that have produced the depletion of GC bases in outward-facing gene arrays. In turn, high AT content exerts a profound effect on their chromatin organization and transcriptional regulation.

Infectious and Inflammatory Sinonasal Diseases.

Rhinosinusitis is a commonly encountered disease. Imaging is not typically required in acute uncomplicated rhinosinusitis; however, it is integral in the evaluation of patients who present with prolonged or atypical symptoms or when acute intracranial complications or alternate diagnoses are suspected. Knowledge of the paranasal sinus anatomy is important to understand patterns of sinonasal opacification. Bacterial, viral, and fungal pathogens are responsible culprits and, with duration of symptoms, serve to categorize infectious sinonasal disease. Several systemic inflammatory and vasculitic processes have a predilection for the sinonasal region. Imaging, along with laboratory and histopathologic analysis, assist in arriving at these diagnoses.

An Intensive Intervention to Reduce Readmissions for Frequently Hospitalized Patients: the CHAMP Randomized Controlled Trial.

BACKGROUND: A small number of patients are disproportionally readmitted to hospitals. The Complex High Admission Management Program (CHAMP) was established as a multidisciplinary program to improve continuity of care and reduce readmissions for frequently hospitalized patients. OBJECTIVE: To compare hospital utilization metrics among patients enrolled in CHAMP and usual care. DESIGN: Pragmatic randomized controlled trial. PARTICIPANTS: Inclusion criteria were as follows: 3 or more, 30-day inpatient readmissions in the previous year; or 2 inpatient readmissions plus either a referral or 3 observation admissions in previous 6 months. INTERVENTIONS: Patients randomized to CHAMP were managed by an interdisciplinary team including social work, physicians, and pharmacists. The CHAMP team used comprehensive care planning and inpatient, outpatient, and community visits to address both medical and social needs. Control patients were randomized to usual care and contacted 18 months after initial identification if still eligible. MAIN MEASURES: Primary outcome was number of 30-day inpatient readmissions 180 days following enrollment. Secondary outcomes were number of hospital admissions, total hospital days, emergency department visits, and outpatient clinic visits 180 days after enrollment. KEY RESULTS: There were 75 patients enrolled in CHAMP, 76 in control. Groups were similar in demographic characteristics and baseline readmissions. At 180 days following enrollment, CHAMP patients had more inpatient 30-day readmissions [CHAMP incidence rate 1.3 (95% CI 0.9-1.8) vs. control 0.8 (95% CI 0.5-1.1), p=0.04], though both groups had fewer readmissions compared to 180 days prior to enrollment. We found no differences in secondary outcomes. CONCLUSIONS: Frequently hospitalized patients experienced reductions in utilization over time. Though most outcomes showed no difference, CHAMP was associated with higher readmissions compared to a control group, possibly due to consolidation of care at a single hospital. Future research should seek to identify subsets of patients with persistently high utilization for whom tailored interventions may be beneficial. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03097640; https://clinicaltrials.gov/ct2/show/NCT03097640.

2,4,6-Tribromophenol Disposition and Kinetics in Pregnant and Nursing Sprague Dawley Rats.

2,4,6-Tribromophenol (TBP, CAS no. 118-79-6) is a brominated chemical used as a precursor, flame retardant, and wood antifungal agent. TBP is detected in environmental matrices and biota, including human breast milk, placenta, and serum. To address reports of TBP accumulation in human placenta and breast milk, studies were conducted to characterize TBP disposition and toxicokinetics in timed-pregnant or nursing Sprague Dawley rats following a single oral dose to the dam. Animals were administered [14C]-TBP (10 µmol/kg, 25 µCi/kg, 4 ml/kg) by gavage on gestation day 12 and 20, or postnatal day 12 and serially euthanized between 15 min and 24 h for collection of blood and tissues from the dam and fetuses/pups. Observed plasma TBP Cmax (3 and 7 nmol/ml) occurred at 15 min in both GD12 and GD20 dams while Cmax (3 nmol/ml) was observed at 30 min for PND12 dams. Concentrations in tissues followed plasma concentrations, with kidneys containing the highest concentrations at 30 min. GD12 litters contained a sustained 0.2%-0.3% of the dose (5-9 nmol/litter) between 15 min and 6 h while GD20 fetuses (2%-3%) and placentas (0.3%-0.5%) had sustained levels between 30 min and 12 h. The stomach contents (approx. 1 nmol-eq/g, 6-12 h), livers (0.04-0.1 nmol-eq/g) and kidneys (0.1-0.2 nmol-eq/g) of PND12 pups increased over time, indicating sustained exposure via milk. Systemic exposure to TBP and its metabolites occurs in both the directly exposed mother and the indirectly exposed offspring and is rapid and persistent after a single dose in pregnant and nursing rats.

Perihematomal edema surrounding spontaneous intracerebral hemorrhage by CT: Ellipsoidal versus morphometric volumetry.

Perihematomal edema (PHE) surrounding intracerebral hemorrhage (ICH) may contribute to disease-associated morbidity. Before quantifying PHE's effects on morbidity, a fast, accurate, and reproducible method for measuring PHE volume is needed. The aim of this study is to demonstrate the use of a semiautomated dual clustering segmentation algorithm to generate PHE volumetrics on noncontrast computed tomography (CT) of the head and compare this technique to physicians' manual calculations.This is a single-center, retrospective imaging study that included head CTs performed from January 2008 to December 2014 on 154 patients with ICH. Subjects ≥ 18 years old who were admitted to the hospital with spontaneous ICH were included. Included subjects had head CTs performed upon admission and within 6 to 24 hours. Two neurologists, 2 neuroradiologists, and a computer program all calculated hemorrhage and PHE volumes. Inter-rater correlation was evaluated using 2 statistical methods: intraclass correlations (ICCs) and limits of agreement (LOA). Additionally, correlation between volumes was separately evaluated using Pearson correlation coefficient.There was an excellent correlation between measurements performed by neurologists and neuroradiologists using ABC/2 for ICH (0.93) and PHE (0.78). There was a good correlation between measurements performed by neurologists using ABC/2 and the volume measurements generated by the algorithm for ICH (0.69) and PHE (0.70). There was a fair correlation between measurements performed by neuroradiologists using ABC/2 and volume measurements generated by the algorithm for ICH (0.47) and good correlation for PHE (0.73).Although the ABC/2 method for measuring PHE is quick and practical, algorithms that do not assume ellipsoidal shape may be more accurate.

The Comprehensive Care Plan: A Patient-Centered, Multidisciplinary Communication Tool for Frequently Hospitalized Patients.

Comprehensive care plans are dynamic documents maintained by an interdisciplinary team that contain specific, actionable information for clinicians and staff across multiple care settings. They promote communication and continuity of care by suggesting communication strategies, medical plans, and psychosocial resources. This article describes the structure and development process of comprehensive care plans for frequently hospitalized patients enrolled in a program designed to improve care for this vulnerable population. These care plans are widely used, with inpatient physicians referring to the care plan in their notes during 92.0% of admissions.

Comparative Molecular Life History of Spontaneous Canine and Human Gliomas.

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.

Correction: Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer.

[This corrects the article DOI: 10.1371/journal.pcbi.1006840.].

Using CT texture analysis to differentiate cystic and cystic-appearing odontogenic lesions.

PURPOSE: Cystic and cystic-appearing odontogenic lesions of the jaw may appear similar on CT imaging. Accurate diagnosis is often difficult although the relationship of the lesion to the tooth root or crown may offer a clue to the etiology. The purpose of this study was to evaluate CT texture analysis as an aid in differentiating cystic and cystic-appearing odontogenic lesions of the jaw. METHODS: This was an IRB-approved retrospective study including 42 pathology-proven dentigerous cysts, 37 odontogenic keratocysts, and 19 ameloblastomas. Each lesion was manually segmented on axial CT images, and textural features were analyzed using an in-house-developed Matlab-based texture analysis program that extracted 47 texture features from each segmented volume. Statistical analysis was performed comparing all pairs of the three types of lesions. RESULTS: Pairwise analysis revealed that nine histogram features, one GLCM feature, three GLRL features, two Laws features, four GLGM features and two Chi-square features showed significant differences between dentigerous cysts and odontogenic keratocysts. Four histogram features and one Chi-square feature showed significant differences between odontogenic keratocysts and ameloblastomas. Two histogram features showed significant differences between dentigerous cysts and ameloblastomas. CONCLUSIONS: CT texture analysis may be useful as a noninvasive method to obtain additional quantitative information to differentiate cystic and cystic-appearing odontogenic lesions of the jaw.

Using texture analysis of head CT images to differentiate osteoporosis from normal bone density.

OBJECTIVES: To investigate the use of texture analysis for the detection of osteoporosis on noncontrast head CTs, and to explore optimal sampling regions within the craniofacial bones. METHODS: In this IRB-approved, retrospective study, the clivus, bilateral sphenoid triangles and mandibular condyles were manually segmented on each noncontrast head CT, and 41 textures features were extracted from 29 patients with normal bone density (NBD); and 29 patients with osteoporosis. Basic descriptive statistics including a false discovery rate correction were performed to evaluate for differences in texture features between the cohorts. RESULS: Sixteen texture features demonstrated significant differences (P < 0.01) between NBD and osteoporosis in the clivus including 4 histogram features, 2 gray-level co-occurrence matrix features, 8 gray-level run-length features and 2 Law's features. Nineteen texture features including 9 histogram features, 1 GLCM features, 2 GLRL features, 5 Law's features and 2 GLGM features demonstrated statistically significant differences in both sides of the sphenoid triangles. A total 24 texture features demonstrated statistically significant differences between normal BMD and osteoporosis in the left sphenoid and a total of 31 texture features in the left condyle. Furthermore, a total of 22 texture features including 6 histogram features, 3 GLCM features, 9 GLRL features, 2 Law's features and 2 GLGM features demonstrated statistically significant differences in both sides of the mandibular condyles. CONCLUSION: The results of this investigation suggest that specific texture analysis features derived from regions of interest placed within multiple sites within the skull base and maxillofacial bones can distinguish between patients with normal bone mineral density compared to those with osteoporosis. This study demonstrates the potential utility of a texture analysis for identification of osteoporosis on head CT, which may help identify patients who have not undergone screening with traditional DXA.

Frequently Hospitalized Patients' Perceptions of Factors Contributing to High Hospital Use.

BACKGROUND: A small proportion of patients accounts for a large proportion of hospitalizations. OBJECTIVE: To obtain patients' perspectives of factors associated with the onset and continuation of high hospital use. DESIGN: Qualitative research study where a research coordinator conducted one-on-one semi-structured interviews. A team of researchers performed inductive coding and analysis. SETTING: A single urban academic hospital. PARTICIPANTS: Patients with two unplanned 30-day readmissions within 12 months and one or more of the following: ≥1 readmission in the last six months, a referral from a clinician, or ≥3 observation visits. RESULTS: Overall, 26 participants completed the interviews. Four main themes emerged. First, major medical problems were universal, but the onset of frequent hospital use varied. Second, participants perceived fluctuations in their course to be related to psychological, social, and economic factors. Social support was perceived as helpful and participants benefited when providing social support to others. Third, episodes of illness varied in onset and generally seemed uncontrollable and often unpredictable to the participants. Fourth, participants strongly desired to avoid hospitalization and typically sought care only after self-management failed. CONCLUSIONS: Emergent themes pointed to factors which influence patients' onset of high hospital use, fluctuations in their illness over time, and triggers to seek care during an episode of illness. These findings enable patients' perspectives to be incorporated into the design of programs serving similar populations of frequently hospitalized patients.

Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer.

Drug resistance in breast cancer cell populations has been shown to arise through phenotypic transition of cancer cells to a drug-tolerant state, for example through epithelial-to-mesenchymal transition or transition to a cancer stem cell state. However, many breast tumors are a heterogeneous mixture of cell types with numerous epigenetic states in addition to stem-like and mesenchymal phenotypes, and the dynamic behavior of this heterogeneous mixture in response to drug treatment is not well-understood. Recently, we showed that plasticity between differentiation states, as identified with intracellular markers such as cytokeratins, is linked to resistance to specific targeted therapeutics. Understanding the dynamics of differentiation-state transitions in this context could facilitate the development of more effective treatments for cancers that exhibit phenotypic heterogeneity and plasticity. In this work, we develop computational models of a drug-treated, phenotypically heterogeneous triple-negative breast cancer (TNBC) cell line to elucidate the feasibility of differentiation-state transition as a mechanism for therapeutic escape in this tumor subtype. Specifically, we use modeling to predict the changes in differentiation-state transitions that underlie specific therapy-induced changes in differentiation-state marker expression that we recently observed in the HCC1143 cell line. We report several statistically significant therapy-induced changes in transition rates between basal, luminal, mesenchymal, and non-basal/non-luminal/non-mesenchymal differentiation states in HCC1143 cell populations. Moreover, we validate model predictions on cell division and cell death empirically, and we test our models on an independent data set. Overall, we demonstrate that changes in differentiation-state transition rates induced by targeted therapy can provoke distinct differentiation-state aggregations of drug-resistant cells, which may be fundamental to the design of improved therapeutic regimens for cancers with phenotypic heterogeneity.

Using CT texture analysis to differentiate between nasopharyngeal carcinoma and age-matched adenoid controls.

OBJECTIVES: To investigate the use of texture analysis to quantitatively distinguish nasopharyngeal carcinoma (NPC) from normal adenoid on CT. METHODS: In this IRB-approved, retrospective study, nasopharyngeal tissues in 13 patients with NPC and 13 control patients were manually contoured, segmented, and imported to an in-house developed texture analysis program, which extracted 41 texture features. Basic descriptive statistics were performed to evaluate for differences in texture parameters between NPC and controls. RESULTS: Statistically significant differences between NPC and controls were seen in 32 of 41 texture features. These significant differences were present in 11 of 12 histogram features, 4 of 5 gray-level co-occurrence matrix features, 7 of 11 gray-level run length features, 4 of 4 gray-level gradient matrix features, and 6 of 9 Laws features. CONCLUSION: Significant differences in many texture features were seen between NPC and normal adenoids. CT texture analysis may aid in differentiating NPC from normal adenoid tissue.

Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer.

Intratumoral heterogeneity in cancers arises from genomic instability and epigenomic plasticity and is associated with resistance to cytotoxic and targeted therapies. We show here that cell-state heterogeneity, defined by differentiation-state marker expression, is high in triple-negative and basal-like breast cancer subtypes, and that drug tolerant persister (DTP) cell populations with altered marker expression emerge during treatment with a wide range of pathway-targeted therapeutic compounds. We show that MEK and PI3K/mTOR inhibitor-driven DTP states arise through distinct cell-state transitions rather than by Darwinian selection of preexisting subpopulations, and that these transitions involve dynamic remodeling of open chromatin architecture. Increased activity of many chromatin modifier enzymes, including BRD4, is observed in DTP cells. Co-treatment with the PI3K/mTOR inhibitor BEZ235 and the BET inhibitor JQ1 prevents changes to the open chromatin architecture, inhibits the acquisition of a DTP state, and results in robust cell death in vitro and xenograft regression in vivo.

Craniofacial Manifestations of Systemic Disorders: CT and MR Imaging Findings and Imaging Approach.

Many systemic diseases or conditions can affect the maxillofacial bones; however, they are often overlooked or incidentally found at routine brain or head and neck imaging performed for other reasons. Early identification of some conditions may significantly affect patient care and alter outcomes. Early recognition of nonneoplastic hematologic disorders, such as thalassemia and sickle cell disease, may help initiate earlier treatment and prevent serious complications. The management of neoplastic diseases such as lymphoma, leukemia, or Langerhans cell histiocytosis may be different if diagnosed early, and metastases to the maxillofacial bones may be the first manifestation of an otherwise occult neoplasm. Endocrinologic and metabolic disorders also may manifest with maxillofacial conditions. Earlier recognition of osteoporosis may alter treatment and prevent complications such as insufficiency fractures, and identification of acromegaly may lead to surgical treatment if there is an underlying growth hormone-producing adenoma. Bone dysplasias sometimes are associated with skull base foraminal narrowing and subsequent involvement of the cranial nerves. Inflammatory processes such as rheumatoid arthritis and sarcoidosis may affect the maxillofacial bones, skull base, and temporomandibular joints. Radiologists should be familiar with the maxillofacial computed tomographic and magnetic resonance imaging findings of common systemic disorders because these may be the first manifestations of an otherwise unrevealed systemic process with potential for serious complications. Online supplemental material is available for this article. ©RSNA, 2018.

Miscellaneous and Emerging Applications of Dual-Energy Computed Tomography for the Evaluation of Intracranial Pathology.

Dual-energy computed tomography (CT) has the potential to improve detection of abnormalities and increase diagnostic confidence in the evaluation of a variety of neurologic conditions by using different x-ray energy-dependent absorption behaviors of different materials. This article reviews the virtual monochromatic imaging applications of dual-energy CT, particularly material decomposition algorithms to improve lesion conspicuity, define lesion-normal tissue interface using different reconstruction techniques, and discuss miscellaneous emerging applications of dual-energy CT for neuroimaging, with an emphasis on their potential clinical utility.

Micro-Credit and Community Wildlife Management: Complementary Strategies to Improve Conservation Outcomes in Serengeti National Park, Tanzania.

Community wildlife management programs in African protected areas aim to deliver livelihood and social benefits to local communities in order to bolster support for their conservation objectives. Most of these benefits are delivered at the community level. However, many local people are also seeking more individual or household-level livelihood benefits from community wildlife management programs because it is at this level that many of the costs of protected area conservation are borne. Because community wildlife management delivers few benefits at this level, support for their conservation objectives amongst local people often declines. The study investigated the implications of this for reducing poaching in Serengeti National Park, Tanzania. Three community wildlife management initiatives undertaken by Park management were compared with regard to their capacity to deliver the individual and household-level benefits sought by local people: community conservation services, wildlife management areas and community conservation banks. Interviews were carried out with poachers and local people from four villages in the Western Serengeti including members of village conservation banks, as well as a number of key informants. The results suggest that community conservation banks could, as a complementary strategy to existing community wildlife management programs, potentially provide a more effective means of reducing poaching in African protected areas than community wildlife management programs alone.