Estimating conflict losses and reporting biases.

Determining the number of casualties and fatalities suffered in militarized conflicts is important for conflict measurement, forecasting, and accountability. However, given the nature of conflict, reliable statistics on casualties are rare. Countries or political actors involved in conflicts have incentives to hide or manipulate these numbers, while third parties might not have access to reliable information. For example, in the ongoing militarized conflict between Russia and Ukraine, estimates of the magnitude of losses vary wildly, sometimes across orders of magnitude. In this paper, we offer an approach for measuring casualties and fatalities given multiple reporting sources and, at the same time, accounting for the biases of those sources. We construct a dataset of 4,609 reports of military and civilian losses by both sides. We then develop a statistical model to better estimate losses for both sides given these reports. Our model accounts for different kinds of reporting biases, structural correlations between loss types, and integrates loss reports at different temporal scales. Our daily and cumulative estimates provide evidence that Russia has lost more personnel than has Ukraine and also likely suffers from a higher fatality to casualty ratio. We find that both sides likely overestimate the personnel losses suffered by their opponent and that Russian sources underestimate their own losses of personnel.

A BAYESIAN NONPARAMETRIC MODEL FOR INFERRING SUBCLONAL POPULATIONS FROM STRUCTURED DNA SEQUENCING DATA.

There are distinguishing features or "hallmarks" of cancer that are found across tumors, individuals, and types of cancer, and these hallmarks can be driven by specific genetic mutations. Yet, within a single tumor there is often extensive genetic heterogeneity as evidenced by single-cell and bulk DNA sequencing data. The goal of this work is to jointly infer the underlying genotypes of tumor subpopulations and the distribution of those subpopulations in individual tumors by integrating single-cell and bulk sequencing data. Understanding the genetic composition of the tumor at the time of treatment is important in the personalized design of targeted therapeutic combinations and monitoring for possible recurrence after treatment. We propose a hierarchical Dirichlet process mixture model that incorporates the correlation structure induced by a structured sampling arrangement and we show that this model improves the quality of inference. We develop a representation of the hierarchical Dirichlet process prior as a Gamma-Poisson hierarchy and we use this representation to derive a fast Gibbs sampling inference algorithm using the augment-and-marginalize method. Experiments with simulation data show that our model outperforms standard numerical and statistical methods for decomposing admixed count data. Analyses of real acute lymphoblastic leukemia cancer sequencing dataset shows that our model improves upon state-of-the-art bioinformatic methods. An interpretation of the results of our model on this real dataset reveals co-mutated loci across samples.

Evaluation of Knee Cartilage Diurnal, Activity, and BMI-Related Variations Using Quantitative T2 Mapping MRI and Fitbit Activity Tracking.

The aim of this study is to evaluate diurnal variation in knee cartilage 3 Tesla magnetic resonance imaging (MRI) T2 mapping relaxation times, as well as activity- and body mass index (BMI)-dependent variability, using quantitative analysis of T2 values from segmented regions of the weight-bearing articular surfaces of the medial and lateral femoral condyles and tibial plateaus. Ten healthy volunteers' daily activity (steps) were tracked with Fitbit pedometers. Sagittal MRI T2 maps were obtained in the morning and afternoon on days 2 and 3. Mean T2 values were analyzed for variation related to the number of steps taken (activity), time of day (diurnal variation), and BMI using mixed effect model. Significant (albeit small) differences in the medial femoral and medial tibial cartilage regions were identified between morning and afternoon scans (diurnal variation). Daily activity did not result in significant changes and increasing BMI only demonstrated a slight increase in T2 values for the lateral tibial plateau. These findings suggest that it may be necessary to control diurnal variation when using quantitative MRI T2 mapping to assess articular cartilage longitudinally in healthy participants. Further investigation is needed to confirm these findings and determine if they also apply to symptomatic patients.

Scapulothoracic pathology: review of anatomy, pathophysiology, imaging findings, and an approach to management.

Symptomatic scapulothoracic disorders, including scapulothoracic crepitus and scapulothoracic bursitis are uncommon disorders involving the scapulothoracic articulation that have the potential to cause significant patient morbidity. Scapulothoracic crepitus is the presence of a grinding or popping sound with movement of the scapula that may or may not be symptomatic, while scapulothoracic bursitis refers to inflammation of bursa within the scapulothoracic articulation. Both entities may occur either concomitantly or independently. Nonetheless, the constellation of symptoms manifested by both entities has been referred to as the snapping scapula syndrome. Various causes of scapulothoracic crepitus include bursitis, variable scapular morphology, post-surgical or post-traumatic changes, osseous and soft tissue masses, scapular dyskinesis, and postural defects. Imaging is an important adjunct to the physical examination for accurate diagnosis and appropriate treatment management. Non-operative management such as physical therapy and local injection can be effective for symptoms secondary to scapular dyskinesis or benign, non-osseous lesions. Surgical treatment is utilized for osseous lesions, or if non-operative management for bursitis has failed. Open, arthroscopic, or combined methods have been performed with good clinical outcomes.

Musculoskeletal Imaging Findings of Hematologic Malignancies.

Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m (99mTc) methylene diphosphonate (MDP) bone scanning, fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. ©RSNA, 2017.

US and MR Imaging of Pectoralis Major Injuries.

During the past 2 decades, the frequency of pectoralis major muscle injuries has increased in association with the increased popularity of bench press exercises. Injury of the pectoralis major can occur at the muscle origin, muscle belly, musculotendinous junction, intratendinous region, and/or humeral insertion-with or without bone avulsion. The extent of the tendon injury ranges from partial to complete tears. Treatment may be surgical or conservative, depending on the clinical scenario and anatomic characteristics of the injury. The radiologist has a critical role in the patient's treatment-first in detecting and then in characterizing the injury. In this article, the authors review the normal anatomy and anatomic variations of the pectoralis major muscle, classifications and typical patterns of pectoralis major injuries, and associated treatment considerations. The authors further provide an instructive guide for ultrasonographic (US) and magnetic resonance (MR) imaging evaluation of pectoralis major injuries, with emphasis on a systematic approach involving the use of anatomic landmarks. After reviewing this article, the reader should have an understanding of how to perform-and interpret the findings of-US and MR imaging of the pectoralis major. The reader should also understand how to classify pectoralis major injuries, with emphasis on the key findings used to differentiate injuries for which surgical management is required from those for which nonsurgical management is required. Familiarity with the normal but complex anatomy of the pectoralis major is crucial for performing imaging-based evaluation and understanding the injury findings. ©RSNA, 2017 Online supplemental material is available for this article.

Inferior glenohumeral ligament (IGHL) complex: anatomy, injuries, imaging features, and treatment options.

The inferior glenohumeral ligament (IGHL) complex is comprised of three components supporting the inferior aspect of the shoulder. It consists of an anterior band, a posterior band, and an interposed axillary pouch. Injuries to the IGHL complex have a unifying clinical history of traumatic shoulder injury, which are often sports or fall-related, with the biomechanical mechanism, positioning of the arm, and individual patient factors determining the specific component of the ligamentous complex that is injured, the location of the injury of those components, and the degree of bone involvement. Several acronyms are employed to characterize these features, specifying whether there is involvement of a portion of the anterior band, posterior band, or midsubstance, and if there is avulsion from the humeral attachment, glenoid attachment, or both. Imaging recommendations for the evaluation of the IGHL complex include magnetic resonance imaging (MRI), and injuries to this complex are best visualized with magnetic resonance arthrography. Additionally, a brief description of clinical management of inferior glenohumeral ligament injuries is included.

Hypertrophic Osteoarthropathy: Clinical and Imaging Features.

Hypertrophic osteoarthropathy (HOA) is a medical condition characterized by abnormal proliferation of skin and periosteal tissues involving the extremities and characterized by three clinical features: digital clubbing (also termed Hippocratic fingers), periostosis of tubular bones, and synovial effusions. HOA can be a primary entity, known as pachydermoperiostosis, or can be secondary to extraskeletal conditions, with different prognoses and management implications for each. There is a high association between secondary HOA and malignancy, especially non-small cell lung cancer. In such cases, it can be considered a form of paraneoplastic syndrome. The most prevalent secondary causes of HOA are pulmonary in origin, which is why this condition was formerly referred to as hypertrophic pulmonary osteoarthropathy. HOA can also be associated with pleural, mediastinal, and cardiovascular causes, as well as extrathoracic conditions such as gastrointestinal tumors and infections, cirrhosis, and inflammatory bowel disease. Although the skeletal manifestations of HOA are most commonly detected with radiography, abnormalities can also be identified with other modalities such as computed tomography, magnetic resonance imaging, and bone scintigraphy. The authors summarize the pathogenesis, classification, causes, and symptoms and signs of HOA, including the genetics underlying the primary form (pachydermoperiostosis); describe key findings of HOA found at various imaging modalities, with examples of underlying causative conditions; and discuss features differentiating HOA from other causes of multifocal periostitis, such as thyroid acropachy, hypervitaminosis A, chronic venous insufficiency, voriconazole-induced periostitis, progressive diaphyseal dysplasia, and neoplastic causes such as lymphoma. ©RSNA, 2016.

Coracoid Process: The Lighthouse of the Shoulder.

The coracoid process is a hook-shaped bone structure projecting anterolaterally from the superior aspect of the scapular neck. Surgeons often refer to the coracoid process as the "lighthouse of the shoulder" given its proximity to major neurovascular structures such as the brachial plexus and the axillary artery and vein, its role in guiding surgical approaches, and its utility as a landmark for other important structures in the shoulder. The coracoid also serves as a critical anchor for many tendinous and ligamentous attachments. These include the tendons of the pectoralis minor, coracobrachialis, and short head of the biceps brachii muscles, and the coracoclavicular, coracohumeral, coracoacromial, and transverse scapular ligaments. Consequently, the coracoid and its associated structures are linked to numerous shoulder pathologic conditions. This article will detail the anatomy of the coracoid and its associated structures and review the clinical and radiologic findings of corresponding pathologic conditions in this region with original illustrations and multimodality imaging examples. Highlighted in this article are the coracoclavicular joint, the classification and management of coracoid fractures, subcoracoid impingement, the coracoacromial arch and subacromial impingement, the coracohumeral ligament and the biceps pulley, the coracoclavicular ligament and its surgical reconstruction, adhesive capsulitis, the suprascapular notch and suprascapular notch impingement, subcoracoid bursitis, coracoid transfer procedures, and coracoid tumors. A brief summary of the pathophysiology, potential causes, and management options for each of the pathologic entities will also be discussed. ©RSNA, 2016.

The Traumatized TFCC: An Illustrated Review of the Anatomy and Injury Patterns of the Triangular Fibrocartilage Complex.

The triangular fibrocartilage complex (TFCC) plays an important role in wrist biomechanics and is prone to traumatic and degenerative injury, making it a common source of ulnar-sided wrist pain. Because of this, the TFCC is frequently imaged, and a detailed understanding of its anatomy and injury patterns is critical in generating an accurate report to help guide treatment. In this review, we provide a detailed overview of TFCC anatomy, its normal appearance on magnetic resonance imaging, the spectrum of TFCC injuries based on the Palmer classification system, and pitfalls in accurate assessment.

Posteromedial Corner of the Knee: The Neglected Corner.

The posteromedial corner of the knee (PMC) is an important anatomic structure that is easily seen but often overlooked on magnetic resonance (MR) images. Whereas the posterolateral corner has been referred to as the "dark side of the knee" by some authors owing to widespread lack of knowledge of its complex anatomy, even less is written about the PMC; yet it is as important as the posterolateral corner in multiligament injuries of the knee. The PMC lies between the posterior margin of the longitudinal fibers of the superficial medial collateral ligament (MCL) and the medial border of the posterior cruciate ligament (PCL). The anatomy of the PMC can be complex and the literature describing it can be confusing, at times oversimplifying it and at other times adding unnecessary complexity. Its most important structures, however, can be described more simply as five major components, and can be better shown with illustrations that emphasize the anatomic distinctions. Injuries to the PMC are important to recognize, as disruption of the supporting structures can cause anteromedial rotational instability (AMRI). Isolated PMC injuries are rare; most occur in conjunction with injuries to other important stabilizing knee structures such as the anterior cruciate ligament (ACL) and PCL. Unrecognized and unaddressed injury of the PMC is one of the causes of ACL and PCL graft failures. Recognition of PMC injuries is critical, as the diagnosis will often change or require surgical management.

Giant cell tumor: rapid recurrence after cessation of long-term denosumab therapy.

We report a case of rapid recurrence of a giant cell tumor (GCT) of the distal radius in a 24-year-old woman following the cessation of long-term denosumab therapy. GCT of bone is a histologically benign tumor with multinucleated giant cells on a background of mononuclear giant cells usually presenting as a well-defined epi-metaphyseal lytic lesion without sclerotic margins. Denosumab, a monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), has proven to be an effective neoadjuvant treatment for GCT. The tumor in this case had demonstrated a good response with sustained control for over 2 years while on denosumab therapy. However, within 2 months of cessation of therapy, the tumor demonstrated rapid recurrence and progression with growth, osteolysis, and increased soft tissue component. Despite reinitiating denosumab therapy, there was progressive tumor growth and destruction, ultimately necessitating below-the-elbow amputation. This case illustrates the need for maintenance of denosumab therapy for GCT of bone or definitive surgical treatment prior to its cessation.

Coronal plane fracture of the femoral condyles: anatomy, injury patterns, and approach to management of the Hoffa fragment.

OBJECTIVE: The purpose of this article is to provide a review of coronal fractures of the femoral condyles, known as Hoffa fractures. This includes a review of the normal anatomy of the femoral condyles, examples of the injury, and postoperative imaging findings after surgical treatments. CONCLUSIONS: Knowledge of anatomy with related pathology, orthopedic trends, imaging findings, and complications, is important in assessing Hoffa fractures.

Turf toe and sesamoiditis: what the radiologist needs to know.

The first metatarsophalangeal (MTP) joint complex is a critical weight-bearing structure important to biomechanics. An acute dorsiflexion injury, named "turf toe," is common among American football and soccer players. "Sesamoiditis" is a name often given for pain arising from the hallux sesamoids in the absence of acute trauma, and may result from a variety of causes. The first MTP joint complex can also be affected by degenerative or inflammatory arthritis, infarct, and infection. This review article will cover the anatomy and biomechanics of the first MTP joint complex, its patterns of injury and pathology, imaging techniques, and management.

Structure and function, injury, pathology, and treatment of the medial collateral ligament of the knee.

The medial collateral ligament (MCL) is the most commonly injured ligament of the knee. There is a spectrum of injury severity, and injuries may be acute or chronic. The MCL is also frequently injured in conjunction with other knee structures. Clinical evaluation of the knee is important to assess the degree of surgical acuity, but magnetic resonance imaging can provide details about the injury that may not be obvious clinically. In addition to injury, MCL bursitis can occur and may be treated with needle aspiration and corticosteroid injection. This review article covers the anatomy and biomechanics of the MCL, its injury patterns and approach to management, and MCL bursitis.

Magnetic resonance detection of kidney iron deposition in sickle cell disease: a marker of chronic hemolysis.

PURPOSE: To study the pattern, etiology, and significance of renal iron accumulation in chronically transfused sickle cell disease (SCD) and thalassemia major (TM) patients using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Magnetic resonance imaging (MRI) was performed in 75 SCD patients, 73 TM patients, and 16 healthy controls. Multiecho gradient echo protocols were used to measure T2* reciprocals (R2*) in the kidney, liver, and heart. Kidney R2* was compared to tissue iron estimates, serum iron markers, and surrogates of intravascular hemolysis by univariate regression. RESULTS: Mean R2* in SCD patients was 55.3+/-45.3 Hz, compared with 22.1+/-11 Hz in TM patients and 21.3+/-5.8 Hz in control subjects (P<0.001). Kidney R2* decreased with advancing age (R2=0.09, P<0.02). Kidney R2* correlated strongly with increased serum lactate dehydrogenase levels found in SCD (R2=0.55, P<0.001), but was independent of hepatic iron concentration and cardiac R2*. Kidney R2* did not correlate with blood pressure, creatinine, cardiac index, or right and left ejection fraction. CONCLUSION: Intravascular hemolysis, not chronic transfusion, causes renal hemosiderosis in SCD. Prospective trials are necessary to determine whether kidney R2* is a biomarker for hemolysis-mediated vascular complications in SCD.

E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC mucin expression in cultured human airway epithelial cells.

In previous work, we showed that epidermal growth factor receptor (EGFR) activation causes mucin expression in airway epithelium in vivo and in human NCI-H292 airway epithelial cells and normal human bronchial epithelial (NHBE) cells in vitro. Here we show that the cell surface adhesion molecule, E-cadherin, promotes EGFR-mediated mucin production in NCI-H292 cells in a cell density- and cell cycle-dependent fashion. The addition of the EGFR ligand, transforming growth factor (TGF)-alpha, increased MUC5AC protein expression markedly in dense, but not in sparse, cultures. MUC5AC-positive cells in dense cultures contained 2 N DNA content and did not incorporate bromodeoxyuridine, suggesting that they develop via cell differentiation and that a surface molecule involved in cell-cell contact is important for EGFR-mediated mucin production. In support of this hypothesis, in dense cultures of NCI-H292 cells and in NHBE cells at air-liquid interface, blockade of E-cadherin-mediated cell-cell contacts decreased EGFR-dependent mucin production. E-cadherin blockade also increased EGFR-dependent cell proliferation and TGF-alpha-induced EGFR tyrosine phosphorylation in dense cultures of NCI-H292 cells, suggesting that E-cadherin promotes EGFR-dependent mucin production and inhibits EGFR-dependent cell proliferation via modulation of EGFR phosphotyrosine levels. Furthermore, in dense cultures, E-cadherin blockade decreased the rate of EGFR tyrosine dephosphorylation, implicating an E-cadherin-dependent protein tyrosine phosphatase in EGFR dephosphorylation. Thus E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC production, and our results suggest that this occurs via a pathway involving protein tyrosine phosphatase-dependent EGFR dephosphorylation.

Risk factors for near-fatal asthma.

BACKGROUND: There is a paucity of lung function data in patients, both before and after episodes of near-fatal asthma (NFA), requiring transient endotracheal intubation and mechanical ventilation. METHODS: Lung function was initially measured in 43 asthmatic patients (age range, 16 to 49 years), who were observed and treated in a tertiary referral asthma clinic and were clinically stable at the time of study. Subsequently, clinical and physiologic follow-up studies were obtained over > 5 years. The primary outcomes were to determine (1) the integrity of lung elastic recoil and (2) the severity of expiratory airflow limitation, and (3) to correlate these outcomes with adverse clinical complications. RESULTS: Fourteen of 26 asthmatic patients (54%) [age range, 30 to 49 years] had significantly reduced lung elastic recoil pressures at all lung volumes compared to 3 of 17 asthmatic patients (18%); p = 0.02 [chi(2) test and Fisher exact test] [age range, 16 to 26 years]. In asthmatic patients between the ages of 30 and 49 years, significant loss of lung elastic recoil was noted in 4 of 10 patients with mild reduction in FEV(1) (FEV(1), > 79% predicted), 6 of 12 patients with moderate reduction in FEV(1) (FEV(1), 61 to 79% predicted), and all 4 patients with severe reduction in FEV(1) (FEV(1), < 61% predicted). In asthmatic patients between the ages of 16 and 26 years, significant loss of lung elastic recoil was noted in 0 of 11 patients with mild reduction in FEV(1), 2 of 5 patients with moderate reduction in FEV(1), and 1 of 1 patient with severe reduction in FEV(1). A subgroup of 10 asthmatic patients (7 men) [mean (+/- SD) age, 37 +/- 11 years] were studied when clinically stable, both before and after an episode of NFA in 8 cases and only after an episode of NFA in 2 additional cases. In 1 of 10 cases, the FEV(1) was mildly reduced, in 4 cases it was moderately reduced, and in 5 cases it was severely reduced, both before and after an episode of NFA. The sensitivity was 90%, the specificity was 61%, the positive predictive value was 41%, and the negative predictive value was 95% for NFA with an FEV(1) < or = 79% predicted or FEV(1)/FVC ratio of < 75%. Prior to an episode of NFA, all 8 asthmatic patients had significant loss of lung elastic recoil pressure, and afterward all 10 had significant loss of lung elastic recoil pressure (ie, less than the predicted normal mean minus 1.64 SD at a total lung capacity [TLC] of 100 to 70% predicted). The sensitivity was 100%, the specificity was 79%, the positive predictive value was 59%, and the negative predictive value was 100% for NFA with the loss of lung elastic recoil. The mean TLC measured with a plethysmograph in 10 patients with NFA was 7.2 +/- 1.41 (124 +/- 16% predicted). The sensitivity for TLC of > 115% predicted was 70%, the specificity was 70%, the positive predictive value was 88%, and the negative predictive value was 41% for NFA. CONCLUSION: A persistent reduction in FEV(1) of < or = 79% predicted or an FEV(1)/FVC ratio of < 75%, and, especially, the loss of lung elastic recoil and hyperinflation at TLC are risk factors for NFA. The loss of lung elastic recoil in asthmatic patients was associated with increased age, duration of disease, and progressive expiratory airflow limitation.

Alveolar and airway sites of nitric oxide inflammation in treated asthma.

The goal of this study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in treated patients with asthma, including response to oral corticosteroids, and correlate these sites with expiratory airflow limitation. In 53 (24 male) patients with asthma, age 43 +/- 23 years (mean +/- SD) and all on inhaled corticosteroids, post 180 microg aerosolized albuterol, FEV(1) was 74 +/- 23% predicted and FEV(1)/FVC was 68 +/- 11%. Exhaled NO at 100 ml/second was 27 +/- 23 ppb (p < 0.001 compared with normal, 12 +/- 15 ppb). Bronchial NO maximal flux was 2.4 +/- 3.1 nl/second (p < 0.001 compared with normal, 0.85 +/- 0.55). Alveolar NO concentration was 7.0 +/- 7.4 ppb (p = 0.01 compared with the normal value, 3.2 +/- 2.0 ppb). There was no significant correlation between FEV(1) % predicted or lung elastic recoil and NO bronchial flux or alveolar concentration. However, there was a weak but significant correlation between NO bronchial flux and alveolar concentration (Spearman r = 0.50, p < 0.001). In 10 subjects with asthma on inhaled corticosteroids, 5 days of 30 mg prednisone resulted in isolated significant decreases in NO alveolar concentration, from 13 +/- 10 to 4 +/- 4 ppb (p = 0.002). Despite treatment, including inhaled corticosteroids, patients with asthma may have ongoing separate airway and alveolar sites of NO inflammation, the latter responsive to oral corticosteroids.