Vascular adhesion protein-1 blockade in primary sclerosing cholangitis: Open-label, multicenter, single-arm, phase II trial.

BACKGROUND: Primary sclerosing cholangitis is a progressive inflammatory liver disease characterized by biliary and liver fibrosis. Vascular adhesion protein-1 (VAP-1) is important in the inflammatory process driving liver fibrosis. We evaluated the safety and efficacy of VAP-1 blockade with a monoclonal antibody (timolumab, BTT1023) in patients with primary sclerosing cholangitis. METHODS: BUTEO was a prospective, single-arm, open-label, multicenter, phase II trial, conducted in 6 centers in the United Kingdom. Patients with primary sclerosing cholangitis aged 18-75 years had an alkaline phosphatase value of >1.5 times the upper limit of normal. The dose-confirmatory stage aimed to confirm the safety of timolumab through the incidence of dose-limiting toxicity and sufficient trough levels of circulating antibody to block VAP-1 function. The primary outcome of the dose-expansion portion of the trial was patient's response to timolumab at day 99, as measured by a reduction in serum alkaline phosphatase by 25% or more from baseline to day 99. RESULTS: Twenty-three patients were recruited: 7 into the initial dose-confirmatory stage and a further 16 into an expansion stage. Timolumab (8 mg/kg) was confirmed to be safe for the duration of administration with sufficient circulating levels. Only 2 of the 18 evaluable patients (11.1%) achieved a reduction in alkaline phosphatase levels of 25% or more, and both the proportion of circulating inflammatory cell populations and biomarkers of fibrosis remained unchanged from baseline. CONCLUSIONS: The BUTEO trial confirmed 8 mg/kg timolumab had no short-term safety signals and resulted in sufficient circulating levels of VAP-1 blocking timolumab. However, the trial was stopped after an interim assessment due to a lack of efficacy as determined by no significant change in serum liver tests.

Enantio- and Regioselective Copper-Catalyzed 1,2-Dearomatization of Pyridines.

A copper-catalyzed dearomative alkynylation of pyridines is reported with excellent regio- and enantioselectivities. The synthetically valuable enantioenriched 2-alkynyl-1,2-dihydropyridine products afforded are generated from the readily available feedstock, pyridine, and commercially available terminal alkynes. The three-component reaction between a pyridine, a terminal alkyne, and methyl chloroformate employs copper chloride and StackPhos, a chiral biaryl P,N- ligand, as the catalytic system. Under mild reaction conditions, the desired 1,2-addition products are delivered in up to 99 % yield with regioselectivity ratios up to 25 : 1 and enantioselectivities values of up to 99 % ee. Activated and non-activated terminal alkynes containing a wide range of functional groups are well tolerated. Even acetylene gas delivered mono-alkynylated products in high yield and ee. Application of the methodology in an efficient enantioselective synthesis of the chiral piperidine indolizidine, coniceine, is reported.

Recent treatment advances and practical management of hepatitis D virus.

Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can only propagate in the presence of hepatitis B virus (HBV). Infection with both HBV and HDV frequently results in more severe disease than HBV alone, with higher instances of cirrhosis, liver failure and hepatocellular carcinoma (HCC). Thus, there is a need for effective treatment for HDV; however, currently approved treatment options are very limited both in terms of their efficacy and availability. This makes the management of HDV a challenge for physicians. In this review, we look at the background, diagnosis and treatment of HDV, informed by our hospital data, to set out the optimal management of HDV; we also explore novel treatment options for this disease.

Transcatheter versus surgical closure of atrial septal defects: a systematic review and meta-analysis of clinical outcomes.

BACKGROUND: Atrial septal defects are a common form of CHD and dependent on the size and nature of atrial septal defects, closure may be warranted. The paper aims to compare outcomes of transcatheter versus surgical repair of atrial septal defects. METHODS: A comprehensive electronic literature search was conducted. Primary studies were included if they compared both closure techniques. Primary outcomes included procedural success, mortality, and reintervention rate. Secondary outcomes included residual defect and mean hospital stay. RESULTS: A total of 33 studies were included in meta-analysis. Mean total hospital stay was significantly shorter in the transcatheter cohort across both the adult (95% confidence interval, mean difference -4.05 (-4.78, -3.32) p < 0.00001) and paediatric populations (95% confidence interval, mean difference -4.78 (-5.97, -3.60) p < 0.00001). There were significantly fewer complications in the transcatheter group across both the adult (odds ratio 0.45, 95% confidence interval, [0.28, 0.72], p < 0.00001) and paediatric cohorts (odds ratio 0.26, 95% confidence interval, [0.14, 0.49], p < 0.00001). No significant difference in overall mortality was found between transcatheter versus surgical closure across the two groups, adult (odds ratio 0.76, 95% confidence interval, [0.40, 1.45], p = 0.41), paediatrics (odds ratio 0.62, 95% confidence interval, [0.21, 1.83], p = 0.39). CONCLUSION: Both transcatheter and surgical approaches are safe and effective techniques for atrial septal defect closure. Our study has demonstrated the benefits of transcatheter closure in terms of lower complication rates and mean hospital stay. However, surgery still has a place for more complex closure and, as we have demonstrated, shows no difference in mortality.

Type 2 Autoimmune Hepatitis and Nonadherence to Medication Correlate With Premature Birth and Risk of Postpartum Flare.

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that affects all ages, including women of childbearing age. Optimal management during pregnancy is poorly defined. We aimed to explore the clinical and biochemical course of AIH in the antenatal and postpartum periods, and assess factors associated with premature birth and postpartum flares. Pregnant women with AIH reviewed in the autoimmune liver disease clinic at the Queen Elizabeth Hospital Birmingham between 2009 and 2020 were identified retrospectively, and clinical, biochemical, and immunological data 1 year before conception to 1 year postpartum were collected. Analysis was performed to identify trends in blood markers over the antenatal period, with an interrupted time series approach used to assess postpartum trends. Data were available for n = 27 pregnancies (n = 20 women), with median gestation of 38 weeks (30% premature) and most having type 1 AIH (78%) and delivering via caesarean section (63%). Levels of alanine transaminase, aspartate transaminase, and immunoglobulin G all declined significantly during gestation, followed by significant step-change increases after delivery. Postpartum flare developed in 58% of pregnancies. AIH type 2 was associated with a higher rate of premature births (67% vs. 19%, P = 0.044), and a trend toward a higher rate of postpartum flare (100% vs. 48%, P = 0.053). Although not significant, medication nonadherence was associated with almost double the risk of prematurity (40% vs. 24%, P = 0.415) and postpartum flare (80% vs. 44%, P = 0.109). Conclusion: Biochemical and immunological remission of AIH occurs during pregnancy, although subsequent postpartum flare is common. Type 2 AIH is associated with a higher risk of premature birth and postpartum flare, although further research is required to validate and explain this finding.

ACR Appropriateness Criteria® Intensive Care Unit Patients.

Chest radiography is the most frequent and primary imaging modality in the intensive care unit (ICU), given its portability, rapid image acquisition, and availability of immediate information on the bedside preview. Due to the severity of underlying disease and frequent need of placement of monitoring devices, ICU patients are very likely to develop complications related to underlying disease process and interventions. Portable chest radiography in the ICU is an essential tool to monitor the disease process and the complications from interventions; however, it is subject to overuse especially in stable patients. Restricting the use of chest radiographs in the ICU to only when indicated has not been shown to cause harm. The emerging role of bedside point-of-care lung ultrasound performed by the clinicians is noted in the recent literature. The bedside lung ultrasound appears promising but needs cautious evaluation in the future to determine its role in ICU patients. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Hemoptysis.

Hemoptysis, the expectoration of blood, ranges in severity from nonmassive to massive. This publication reviews the literature on the imaging and treatment of hemoptysis. Based on the literature, the imaging recommendations for massive hemoptysis are both a chest radiograph and CT with contrast or CTA with contrast. Bronchial artery embolization is also recommended in the majority of cases. In nonmassive hemoptysis, both a chest radiograph and CT with contrast or CTA with contrast is recommended. Bronchial artery embolization is becoming more commonly utilized, typically in the setting of failed medical therapy. Recurrent hemoptysis, defined as hemoptysis that recurs following initially successful cessation of hemoptysis, is best reassessed with a chest radiograph and either CT with contrast or CTA with contrast. Bronchial artery embolization is increasingly becoming the treatment of choice in recurrent hemoptysis, with the exception of infectious causes such as in cystic fibrosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Rib Fractures.

Rib fractures are the most common thoracic injury after minor blunt trauma. Although rib fractures can produce significant morbidity, the diagnosis of injuries to underlying organs is arguably more important as these complications are likely to have the most significant clinical impact. Isolated rib fractures have a relatively low morbidity and mortality and treatment is generally conservative. As such, evaluation with standard chest radiographs is usually sufficient for the diagnosis of rib fractures, and further imaging is generally not appropriate as there is little data that undiagnosed isolated rib fractures after minor blunt trauma affect management or outcomes. Cardiopulmonary resuscitation frequently results in anterior rib fractures and chest radiographs are usually appropriate (and sufficient) as the initial imaging modality in these patients. In patients with suspected pathologic fractures, chest CT or Tc-99m bone scans are usually appropriate and complementary modalities to chest radiography based on the clinical scenario. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Lung Cancer Screening.

Lung cancer remains the leading cause of cancer death in both men and women. Smoking is the single greatest risk factor for the development of lung cancer. For patients between the age of 55 and 80 with 30 or more pack years smoking history who currently smoke or who have quit within the last 15 years should undergo lung cancer screening with low-dose CT. In patients who do not meet these criteria but who have additional risk factors for lung cancer, lung cancer screening with low-dose CT is controversial but may be appropriate. Imaging is not recommended for lung cancer screening of patient younger than 50 years of age or patients older than 80 years of age or patients of any age with less than 20 packs per year history of smoking and no additional risk factor (ie, radon exposure, occupational exposure, cancer history, family history of lung cancer, history of COPD, or history of pulmonary fibrosis). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Variabilities of Magnetic Resonance Imaging-, Computed Tomography-, and Positron Emission Tomography-Computed Tomography-Based Tumor and Lymph Node Delineations for Lung Cancer Radiation Therapy Planning.

PURPOSE: To investigate interobserver delineation variability for gross tumor volumes of primary lung tumors and associated pathologic lymph nodes using magnetic resonance imaging (MRI), and to compare the results with computed tomography (CT) alone- and positron emission tomography (PET)-CT-based delineations. METHODS AND MATERIALS: Seven physicians delineated the tumor volumes of 10 patients for the following scenarios: (1) CT only, (2) PET-CT fusion images registered to CT ("clinical standard"), and (3) postcontrast T1-weighted MRI registered with diffusion-weighted MRI. To compute interobserver variability, the median surface was generated from all observers' contours and used as the reference surface. A physician labeled the interface types (tumor to lung, atelectasis (collapsed lung), hilum, mediastinum, or chest wall) on the median surface. Contoured volumes and bidirectional local distances between individual observers' contours and the reference contour were analyzed. RESULTS: Computed tomography- and MRI-based tumor volumes normalized relative to PET-CT-based volumes were 1.62 ± 0.76 (mean ± standard deviation) and 1.38 ± 0.44, respectively. Volume differences between the imaging modalities were not significant. Between observers, the mean normalized volumes per patient averaged over all patients varied significantly by a factor of 1.6 (MRI) and 2.0 (CT and PET-CT) (P=4.10 × 10-5 to 3.82 × 10-9). The tumor-atelectasis interface had a significantly higher variability than other interfaces for all modalities combined (P=.0006). The interfaces with the smallest uncertainties were tumor-lung (on CT) and tumor-mediastinum (on PET-CT and MRI). CONCLUSIONS: Although MRI-based contouring showed overall larger variability than PET-CT, contouring variability depended on the interface type and was not significantly different between modalities, despite the limited observer experience with MRI. Multimodality imaging and combining different imaging characteristics might be the best approach to define the tumor volume most accurately.

ACR Appropriateness Criteria® Suspected Pulmonary Hypertension.

Pulmonary hypertension may be idiopathic or related to a large variety of diseases. Various imaging examinations that may be helpful in diagnosing and determining the etiology of pulmonary hypertension are discussed. Imaging examinations that may aid in the diagnosis of pulmonary hypertension include chest radiography, ultrasound echocardiography, ventilation/perfusion scans, CT, MRI, right heart catheterization, pulmonary angiography, and fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Apparent diffusion coefficient (ADC) change on repeated diffusion-weighted magnetic resonance imaging during radiochemotherapy for non-small cell lung cancer: A pilot study.

OBJECTIVES: Serial diffusion-weighted magnetic resonance imaging (DW-MRI) during radiochemotherapy of non-small cell lung cancer (NSCLC) is analyzed to investigate the apparent diffusion coefficient (ADC) as a potential biomarker for tumor response. METHODS: Ten patients underwent DW-MRI prior to and at three and six weeks during radiochemotherapy. Three methods of contouring primary tumors (PT) were performed to evaluate the impact of tumor heterogeneity on ADC values: PTT: whole tumor volume; PTT-N: PTT-necrosis; PTL: small volume of presumed active tumor with low ADC value. Pretreatment and during-treatment absolute ADC values and ADC value changes were analyzed for PT and involved lymph nodes (LN). RESULTS: ADC values for PTT, PTT-N, PTL and LN increased by 8-14% (PT) and 15% (LN) at three weeks, and 19-26% and 23% at 6 weeks post initial treatment (p=0.04-0.002). Average percent ADC value increase was smaller than tumor volume regression (p=0.06-0.0005). Patients with overall survival <12 months had a lower increase of ADC values compared to longer surviving patients (p=0.008 for PTT). CONCLUSIONS: Significant ADC value increases during radiochemotherapy for non-small cell lung cancer were observed. ADC value change during treatment appears to be an independent marker of patient outcome and warrants further investigation.

Estimation of optimal b-value sets for obtaining apparent diffusion coefficient free from perfusion in non-small cell lung cancer.

The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR ≈ 4500 ms, TE = 74 ms, eight b-values of 0-1000 µs µm(-2), pixel size = 1.98 × 1.98 mm(2), slice thickness = 6 mm, interslice gap = 1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 µs µm(-2) from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 µs µm(-2) were not significantly different from ADCIVIM values (p > 0.05, paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets-0-1000; 50-1000; 100-1000; 500-1000; and 250 and 800 µs µm(-2) were significantly different from the ADCIVIM values. From Rician noise simulation using b-value pairs, there was a wide range of acceptable b-value pairs giving small RMSE of ADC values relative to ADCIVIM. The pairs for small RMSE had lower b-values as the noise level increased. ADC values of a two b-value set-250 and 1000 µs µm(-2), and all three b-value sets with 250, 1000 µs µm(-2) and an intermediate value approached ADCIVIM, with relative noise comparable to that of ADCIVIM. These sets may be used in lung tumours using comparatively short scan and post-processing times. Rician noise simulation suggested that the b-values in the vicinity of these experimental best b-values can be used with error within an acceptable limit. It also suggested that the optimal sets will have lower b-values as the noise level becomes higher.

Total artificial heart implantation: clinical indications, expected postoperative imaging findings, and recognition of complications.

OBJECTIVE: The purposes of this article are to review the treatment options for late-stage biventricular heart failure, discuss the clinical indications for total artificial heart (TAH) implantation, illustrate the expected imaging findings after uncomplicated TAH implantation, and highlight the radiologic findings of common and uncommon complications associated with TAH implantation through case examples. CONCLUSION: TAH implantation is an effective therapeutic option for the treatment of patients with end-stage biventricular heart failure. The duration of implantation varies depending on a particular patient's medical condition and the eventual availability of a human heart for orthotopic transplantation. TAH recipients often undergo imaging with conventional radiography, CT, or both for the assessment of device-related issues, many of which are life-threatening and require emergency management. As the clinical use of the TAH increases and becomes more commonplace, it is imperative that radiologists interpreting imaging studies recognize both the expected and the unexpected imaging findings that affect patient care.

Use of a hybrid iterative reconstruction technique to reduce image noise and improve image quality in obese patients undergoing computed tomographic pulmonary angiography.

PURPOSE: To determine whether an iterative reconstruction (IR) technique (iDose, Philips Healthcare) can reduce image noise and improve image quality in obese patients undergoing computed tomographic pulmonary angiography (CTPA). MATERIALS AND METHODS: The study was Health Insurance Portability and Accountability Act compliant and approved by our institutional review board. A total of 33 obese patients (average body mass index: 42.7) underwent CTPA studies following standard departmental protocols. The data were reconstructed with filtered back projection (FBP) and 3 iDose strengths (iDoseL1, iDoseL3, and iDoseL5) for a total of 132 studies. FBP data were collected from 33 controls (average body mass index: 22) undergoing CTPA. Regions of interest were drawn at 6 identical levels in the pulmonary artery (PA), from the main PA to a subsegmental branch, in both the control group and study groups using each algorithm. Noise and attenuation were measured at all PA levels. Three thoracic radiologists graded each study on a scale of 1 (very poor) to 5 (ideal) by 4 categories: image quality, noise, PA enhancement, and "plastic" appearance. Statistical analysis was performed using an unpaired t test, 1-way analysis of variance, and linear weighted κ. RESULTS: Compared with the control group, there was significantly higher noise with FBP, iDoseL1, and iDoseL3 algorithms (P<0.001) in the study group. There was no significant difference between the noise in the control group and iDoseL5 algorithm in the study group. Analysis within the study group showed a significant and progressive decrease in noise and increase in the contrast-to-noise ratio as the level of IR was increased (P<0.001). Compared with FBP, readers graded overall image quality as being higher using iDoseL1 (P=0.0018), iDoseL3 (P<0.001), and iDoseL5 (P<0.001). Compared with FBP, there was subjective improvement in image noise and PA enhancement with increasing levels of iDose. CONCLUSION: The use of an IR technique leads to qualitative and quantitative improvements in image noise and image quality in obese patients undergoing CTPA.

Tumoral calcinosis: pearls, polemics, and alternative possibilities.

Massive periarticular calcinosis of the soft tissues is a unique but not rare radiographic finding. On the contrary, tumoral calcinosis is a rare familial disease. Unfortunately, the term tumoral calcinosis has been liberally and imprecisely used to describe any massive collection of periarticular calcification, although this term actually refers to a hereditary condition associated with massive periarticular calcification. The inconsistent use of this term has created confusion throughout the literature. More important, if the radiologist is unfamiliar with tumoral calcinosis or disease processes that mimic this condition, then diagnosis could be impeded, treatment could be delayed, and undue alarm could be raised, possibly leading to unwarranted surgical procedures. The soft-tissue lesions of tumoral calcinosis are typically lobulated, well-demarcated calcifications that are most often distributed along the extensor surfaces of large joints. There are many conditions with similar appearances, including the calcinosis of chronic renal failure, calcinosis universalis, calcinosis circumscripta, calcific tendonitis, synovial osteochondromatosis, synovial sarcoma, osteosarcoma, myositis ossificans, tophaceous gout, and calcific myonecrosis. The radiologist plays a critical role in avoiding unnecessary invasive procedures and in guiding the selection of appropriate tests that can result in a conclusive diagnosis of tumoral calcinosis.

Electronic publishing in radiology: beginnings, current status, and expanding horizons.

Electronic publishing in radiology began in the 1980s and gathered momentum as use of the personal computer and subsequently the World Wide Web became commonplace. The ease of access and wide distribution that the Internet affords have presented both experts and lay users with the challenge of distinguishing reliable from unreliable material. In the field of radiology, peer-reviewed journals, the sine qua non of reliability in the scientific realm, began to appear in online versions in 1988, and now, nearly all such journals currently have online versions. Electronic versions of textbooks and textbook-like material have become more common, although the vast majority of publishers' catalogs are traditional print books. Electronic material is more common in the fields of internal, emergency, and family medicine than in the field of diagnostic radiology. The latest publishing medium is the personal digital assistant. Challenges that face electronic publishing include the issues of permanent archiving, citation, and indexing. Peer review seems to be the best method for distinguishing reliable from unreliable information. The use of Web technology has improved the logistics of peer review, and some journals have begun posting peer reviews themselves on the Web alongside peer-reviewed articles. Electronic publishing has changed the manner in which radiologists obtain information, providing wider, more immediate access.

Electronic publishing in radiology: economics and the future.

Scholarly publishing is a large market involving thousands of peer-reviewed journals but a decreasing number of publishers. An economic model can be described in which authors give their work to publishers who then sell access to this work. Because each published article is a unique work with few if any substitutes, publishers have some degree of monopoly power and can price their products accordingly. The advent of desktop publishing using personal computers made it possible for individuals to publish material without publishers, an activity that gained momentum when the publishing medium shifted from paper to electronic, and from electronic publishing to the Internet. This activity destabilized the industry, and in the rush to gain market share by providing free content, unsustainable business models were created. Scholarly publishing is now dominated by a small number of multinational corporations that acquired many smaller publishing operations. As these companies have exercised their monopoly power, an open access movement has gained traction in which authors (or their institutions) initially pay for publication, but readers have free and open access to the published articles. This movement is in diametric opposition to the commercial publishing model, and it remains to be seen whether and how well the two can coexist in the future.