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Τρίτη, 21 Νοεμβρίου 2017

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Global impact of radiotherapy in oncology: Saving one million lives by 2035

Cancer is a group of over 200 distinct diseases with a common fatal outcome if not treated. In 2016, almost 9 million patients died of cancer, an increase of 18% in just the last ten years [1]. Moreover, in parallel with the predicted rise in worldwide cancer cases from the current 15 million to 24 million in two decades, the annual cancer deaths are expected to amount to 14.5 million by 2035 [2]. The good news is there are possibilities to bend this devastating curve: wide implementation of the current cancer prevention efforts will reduce the projected numbers of all cancers by 40–50%, while early diagnosis and advances in cancer treatment resulted in doubling of long-term survival in the past 40 years [3].

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Important ESTRO dates



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Contents



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Functional brain networks involved in decision-making under certain and uncertain conditions

Abstract

Purpose

The aim of this study was to describe imaging markers of decision-making under uncertain conditions in normal individuals, in order to provide baseline activity to compare to impaired decision-making in pathological states.

Methods

In this cross-sectional study, 19 healthy subjects ages 18–35 completed a novel decision-making card-matching task using a Phillips T3 Scanner and a 32-channel head coil. Functional data were collected in six functional runs. In one condition of the task, the participant was certain of the rule to apply to match the cards; in the other condition, the participant was uncertain. We performed cluster-based comparison of the two conditions using FSL fMRI Expert Analysis Tool and network-based analysis using MATLAB.

Results

The uncertain > certain comparison yielded three clusters—a midline cluster that extended through the midbrain, the thalamus, bilateral prefrontal cortex, the striatum, and bilateral parietal/occipital clusters. The certain > uncertain comparison yielded bilateral clusters in the insula, parietal and temporal lobe, as well as a medial frontal cluster. A larger, more connected functional network was found in the uncertain condition.

Conclusion

The involvement of the insula, parietal cortex, temporal cortex, ventromedial prefrontal cortex, and orbitofrontal cortex of the certain condition reinforces the notion that certainty is inherently rewarding. For the uncertain condition, the involvement of the prefrontal cortex, parietal cortex, striatum, thalamus, amygdala, and hippocampal involvement was expected, as these are areas involved in resolving uncertainty and rule updating. The involvement of occipital cortical involvement and midbrain involvement may be attributed to increased visual attention and increased motor control.



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Evaluating the Predictive Ability of Initial Staging F-18 FDG PET/CT for the Prognosis of Non-Hodgkin Malignant Lymphoma Patients Who Underwent Stem Cell Transplantation

Abstract

Objectives

This study aimed to determine the value of clinical prognostic factors and semiquantitative metabolic parameters from initial staging fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in non-Hodgkin lymphoma (NHL) patients treated with stem cell transplantation (SCT).

Methods

A total of 39 malignant lymphoma patients who underwent initial staging F-18 FDG PET/CT were enrolled in this study. SUVmax, MTV_wb, and TLG_wb were measured during the initial staging PET/CT. Receiver operating characteristic curve (ROC) analysis was adopted to dichotomize continuous variables. Log-rank test and Cox proportional hazard regression analysis were used to evaluate disease-free survival (DFS) rate.

Results

Among the 39 patients with malignant lymphoma, 17 (43.6%) had a relapse. For several clinical factors such as age, ECOG performance score, AMC/ALC score, stages, and revised International Prognostic Index score, differences between the two dichotomized groups were statistically insignificant. In univariate analysis, DFS estimates were 71.0 ± 7.8 months and 18.0 ± 5.9 months in high-SUVmax and low-SUVmax group, respectively (P < 0.01). For MTV_wb, DFS estimates were 46.6 ± 12.4 months and 69.1 ± 8.5 months in high-MTV_wb and low-MTV_wb group, respectively (P = 0.12). For TLG_wb, DFS estimates were 65.3 ± 7.5 months and 13.7 ± 8.6 months in high-TLG_wb and low-TLG_wb group, respectively (P = 0.02). In Cox proportional hazard regression analysis, only MTV_wb showed statistical significance (HR 3.01, 95% CI 1.04–8.74, P = 0.04).

Conclusion

In NHL patients treated with SCT, the MTV_wb of initial staging F-18 FDG PET/CT was an independent prognostic factor.



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Imaging characteristics of subcutaneous amyloid deposits in diabetic patients: the “insulin ball”

Abstract

Objective

The purpose of this study was to describe the imaging characteristics of subcutaneous amyloid deposits occurring at sites of insulin injection, commonly known as "insulin balls," in diabetic patients on ultrasound, CT, and MRI with pathologic correlation.

Materials and methods

We retrospectively reviewed the radiographic findings of 14 lesions in 9 patients diagnosed with subcutaneous amyloid deposits at our institution between 2005–2015. Three board-certified radiologists analyzed the following: (1) the shape, size, margin, morphologic characteristics, and blood flow on US using the color Doppler signal, (2) shape, size, margin, attenuation, and presence or absence of contrast enhancement on CT, and (3) shape, size, margin, signal intensity, and presence or absence of contrast enhancement on MRI.

Results

All lesions showed ill-defined hypovascular subcutaneous nodules with irregular margins. The median diameter of lesions was 50.4 mm on US, 46.8 mm on CT, and 51.4 mm on MRI. The internal echogenicity of subcutaneous amyloid deposits was hypoechoic and heterogeneous on US. All lesions showed isodensity compared to muscle with irregular margins and minimal contrast enhancement on CT. Both T1- and T2-weighted MR images showed low signal intensity compared with subcutaneous fat. Normal diffusion and minimal contrast enhancement were seen.

Conclusions

Subcutaneous amyloid deposits which cause insulin resistance are typically ill-defined and heterogeneous hypovascular subcutaneous nodules with irregular margins on imaging that correspond to insulin injection sites. It is also characteristic that T2WI shows low intensity compared with fat on MRI, reflective of the amyloid content.



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Slowly growing mass on the left shoulder



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Conservatively treated knee injury is associated with knee cartilage matrix degeneration measured with MRI-based T2 relaxation times: data from the osteoarthritis initiative

Abstract

Objective

To investigate the association of cartilage degeneration with previous knee injuries not undergoing surgery, determined by morphologic and quantitative 3-T magnetic resonance imaging (MRI).

Materials and methods

We performed a nested cross-sectional study of right knee MRIs from participants in the Osteoarthritis Initiative (OAI) aged 45–79 with baseline Kellgren-Lawrence score of 0–2. Cases were 142 right knees of patients with self-reported history of injury limiting the ability to walk for at least 2 days. Controls were 426 right knees without history of injury, frequency-matched to cases on age, BMI, gender, KL scores and race (1:3 ratio). Cases and controls were compared using covariate-adjusted linear regression analysis, with the outcomes of region-specific T2 mean, laminar analysis and heterogeneity measured by texture analysis to investigate early cartilage matrix abnormalities and the Whole-Organ Magnetic Resonance Imaging Score (WORMS) to investigate morphologic knee lesions.

Results

Compared to control subjects, we found significantly higher mean T2 values in the injury [lateral tibia (28.10 ms vs. 29.11 ms, p = 0.001), medial tibia (29.70 ms vs. 30.40 ms, p = 0.014) and global knee cartilage (32.73 ms vs. 33.29 ms, p = 0.005)]. Injury subjects also had more heterogeneous cartilage as measured by GLCM texture contrast, variance and entropy (p < 0.05 in 14 out of 18 texture parameters). WORMS gradings were not significantly different between the two groups (p > 0.05).

Conclusion

A history of knee injury not treated surgically is associated with higher and more heterogeneous T2 values, but not with morphologic knee abnormalities. Our findings suggest that significant, conservatively treated knee injuries are associated with permanent cartilage matrix abnormalities.



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Correction to: Highlights of the annual scientific meeting of the 24th congress of the European Society of Musculoskeletal Radiology (ESSR) 2017

Abstract

The original version of this article unfortunately contained mistakes. The name and affiliations of Luca Maria Sconfienza are already corrected on this article.



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Southwick angle measurements and SCFE slip severity classifications are affected by frog-lateral positioning

Abstract

Objective

Slipped capital femoral epiphysis (SCFE) is a hip disorder where the femoral head slips relative to the neck at the physis. Appropriate treatment of SCFE depends on the severity of the slip, commonly categorised using the Southwick (SW) angle. The SW angle is measured in the frog-lateral leg position, which can be painful and potentially unattainable for patients. The purpose of this study is to determine how errors in frog-lateral radiograph positioning affect measured SW angles and slip classifications.

Methods

Models of SCFE hips were produced from one CT scan of a normal hip; 360 deformities were created. SW angles were measured from a simulated frog-lateral position. Femoral lateral head-neck angles (LHNA; equivalent to SW in incorrect frog-lateral plane) were measured over a range of 837 incorrect frog-lateral leg positions with positioning errors in flexion and/or internal/external rotation.

Results

Seventy-six per cent of all imaging position-deformity combinations had error in the reported angle (>1° difference between LHNA and SW). Of those, 70% had <5°, 24% had 5° to 10°, and 6% had >10° of error from the actual SW angle. Three per cent of LHNAs that had >10° error resulted from <10° of positioning error.

Conclusions

If the patient is limited in flexion or external rotation, more diagnostic testing should be considered if error in the reported slip measurement would affect treatment decisions or if accurate severity classification is needed for research. Small positioning errors in moderate and severe slips can cause a > 10° LHNA error; additional three-dimensional imaging should be considered.



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Undifferentiated pleomorphic sarcoma: indolent, tail-like recurrence of a high-grade tumor

Abstract

Recurrence of a soft tissue sarcoma typically manifests as a round or oval mass at imaging, and recurrent high-grade soft tissue sarcomas generally enlarge relatively rapidly. We present a case of high-grade undifferentiated pleomorphic sarcoma in the calf of a 48-year-old male that recurred as a thin, curvilinear "tail" of enhancing tissue at magnetic resonance imaging (MRI), with extremely indolent growth over a 7-year period. The unusual imaging finding of a slowly enlarging "tail" should not be dismissed as postoperative changes, even for a high-grade soft tissue sarcoma.



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Is lead shielding of patients necessary during fluoroscopic procedures? A study based on kyphoplasty

Abstract

Objective

To determine the benefits, risks, and limitations associated with wrapping a patient with lead shielding during fluoroscopy-guided kyphoplasty procedures as a way to reduce operator radiation exposure.

Materials and methods

An anthropomorphic phantom was used to mimic a patient undergoing a kyphoplasty procedure under fluoroscopic guidance. Radiation measurements of the air kerma rate (AKR) were made at several locations and under various experimental conditions. First, AKR was measured at various angles along the horizontal plane of the phantom and at varying distances from the phantom, both with and without a lead apron wrapped around the lower portion of the phantom (referred to here as phantom shielding). Second, the effect of an operator's apron was simulated by suspending a lead apron between the phantom and the measurement device. AKR was measured for the four shielding conditions—phantom shielding only, operator apron only, both phantom shielding and operator apron, and no shielding. Third, AKR measurements were made at various heights and with varying C-arm angle.

Results

At all locations, the phantom shielding provided no substantial protection beyond that provided by an operator's own lead apron. Phantom shielding did not reduce AKR at a height comparable to that of an operator's head.

Conclusions

Previous reports of using patient shielding to reduce operator exposure fail to consider the role of an operator's own lead apron in radiation protection. For an operator wearing appropriate personal lead apparel, patient shielding provides no substantial reduction in operator dose.



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Spontaneous shrinkage of solitary osteochondromas

Abstract

Objective

Osteochondromas are the most common benign bone tumors, and thus far, their spontaneous shrinkage is considered a rare phenomenon. This study was designed to investigate the exact ratio of remission to progressive or stable cases and analyze the mechanism of tumor regression on the basis of existing theories.

Materials and methods

We retrospectively collected images of solitary osteochondromas in patients from 1992 to 2013, excluding cases involving short-term follow-up periods and follow-up periods that ended before growth plate closure. A total of 121 patients were diagnosed and screened for study inclusion. Tumor shrinkage was measured by assessing three points on tumor contours to determine if they had regressed or vanished. Patterns of shrinkage were further divided on the basis of mechanisms described as incorporation, absorption, and fracture.

Results

Seventeen patients (mean age at initial diagnosis 13.1 years) met the study inclusion criteria. Tumor morphological classifications were pedunculated (10 cases) and sessile (7 cases). Osteochondroma shrinkage was the most common outcome (8 cases), followed by stable osteochondromas (6 cases), and osteochondromas that had progressed (3 cases). Tumors with sessile morphology were more prone to shrinkage (6 of 7 cases) compared with those of pedunculated morphology (2 of 10 cases; p = 0.015). Among pedunculated cases, tumor shrinkage was via absorption. The timing of tumor growth cessation was related to the pattern of tumor shrinkage. Absorption mostly followed tumor growth cessation, whereas incorporation mostly preceded tumor growth cessation.

Conclusion

The shrinkage of osteochondromas appears less rare than was originally thought.



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Slowly growing mass on the left shoulder



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Assessment of hindfoot alignment using MRI and standing hindfoot alignment radiographs (Saltzman view)

Abstract

Objective

To compare the hindfoot alignment measured on standing HAV radiographs (Saltzman view) and on non-weight-bearing coronal MR images.

Materials and methods

The apparent moment arm was measured on weight-bearing conventional radiographs (Saltzman views) and on MRIs of the ankle in 50 consecutive patients (mean age, 54 years; age range, 18–77 years). The evaluation was performed independently by three readers using analogous reference points for both methods. Positive values were assigned when the deepest point of the calcaneus was lateral to the tibial axis as valgus, negative values as varus. The intertechnique agreement and correlation for the measurements performed with HAV radiographs and MRI were assessed for each reader using the Bland-Altman method and the Pearson correlation coefficient, respectively. The interobserver agreement was assessed using the intraclass correlation coefficient.

Results

The means of apparent moment arms, with the standard deviation (SD) in parentheses, of three readers were +2.0 (±8.4) mm, +1.5 (±6.6) mm and −1.4 (±8.2) mm on HAV radiographs and +4.6 (±7.4) mm, +6.3 (±5.3) mm and +5.4 (±6.4) mm on MRI. The Bland-Altman analysis found a systematic bias for all three readers, corresponding to an overestimation of measurements with MRI (systematic bias ranging from 2.6 to 4.8 mm). The intertechnique correlation was found moderate to high. The Pearson coefficients for the three readers were 0.75, 0.64 and 0.65. The interobserver agreement among the three readers was 0.72, 0.77 and 0.68 for HAV, MRI and both modalities together, respectively.

Conclusion

Hindfoot alignment can be estimated on MRI but the correlation between the values on HAV radiographs and MR images is only moderate with a tendency to increased positive values (valgization) on MR images.



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Highlights of the annual scientific meeting of the 24th congress of the European Society of Musculoskeletal Radiology (ESSR) 2017

Abstract

This paper summarizes the main aspects of the 24th Annual Scientific Meeting of the European Society of Musculoskeletal Radiology (ESSR), which was hosted in Bari (Italy) in June 2017.



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Intraosseous migration of tendinous calcifications: two case reports

Abstract

Calcific tendinopathy of the rotator cuff is a common cause of shoulder pain. Inflammation of the rotator cuff tendons may be complicated by adjacent bone erosion and subsequent migration of calcific deposits within the bone resulting in marrow inflammation. Bone marrow involvement is not readily visible using X-ray and ultrasound (US) and further testing is necessary. Magnetic resonance imaging (MRI) is a highly sensitive technique that can detect a focal bone T1 and T2-weighted hypointensity with bone marrow edema-like signal and cortical erosion. These findings can mislead the radiologist by suggesting an infectious or neoplastic lesion, often requiring further evaluation with computed tomography (CT) and biopsy. We report two cases of patients with shoulder pain in which different radiological approaches were used with pathological confirmation in one of them. In the first case, MRI revealed significant bone involvement in the head of the humerus and cortical erosion of the greater tuberosity. A CT examination and a biopsy was necessary for a final diagnosis of inflammatory bone reaction from intraosseous migration of tendinous calcifications. In the second case, similar MRI findings prompted re-evaluation of imaging to make a diagnosis of intraosseous migration of tendinous calcifications, obviating the need to perform CT and biopsy. We illustrate MRI signs of this complication that we think would allow to narrow the differential diagnosis potentially avoiding biopsy and additional CT examinations.



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Subfascial fat herniation: sonographic features of back mice

Abstract

Three adult patients are described with sonographic features of subfascial fat hernation. Each patient presented to the musculoskeletal ultrasound department at our institution for the evaluation of a palpable mass of the low back. Subfascial fat hernation, also known as back mice and fibro-fatty nodule, are an uncommon cause of a palpable mass in the low back or low back pain. They are small mobile subcutaneous nodules in a characteristic location near the posterior superior iliac spine. This entity has not been described in the radiology literature. These cases are presented in order to demonstrate the sonographic findings of back mice and to describe key anatomic features.



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Combined classical spindle cell/pleomorphic lipoma spectrum imaging and clinical data

Abstract

Objectives

Compile the largest study to date on the imaging and clinical features of the classic spindle cell/pleomorphic lipoma spectrum and suggest this diagnosis be included in the differential for benign and malignant macroscopic fat-containing soft tissue masses regardless of the mass location or patient demographics.

Materials and methods

An institutional search was performed to identify all available classic-type spindle cell/pleomorphic lipomas with available demographic and imaging data. Images and reports were analyzed by one MSK-trained radiologist and radiographic, anatomic and clinical data were recorded. Additionally, a literature search was performed to identify studies describing the spindle cell lipoma spectrum imaging features and were combined with institutional data.

Results

Forty-two institutional cases were identified, 37 of which had MRIs performed among which 21 had images available (T1- and T2-weighted pulse sequences) for review while the remainder had outside reports detailing the mass imaging features. There was a mean age of 57 with 79% of cases occurring in males. Contrary to prior reports, 57% of masses were subcutaneous, and the neck and back region accounted for 26% of cases. When the institutional cases were combined with available data in the literature, there was a new sample size of 91 masses, 74 of which had MRI and/or CT data. Eighty-seven percent of masses were heterogeneous, 51% were composed of less than 75% fat, 65% were in the back, neck or shoulder region, 27% of masses were deep and 91% demonstrated enhancement. Eighty-two percent of patients were males with a mean age of 58 at excision.

Conclusion

Imaging features, patient demographics and tumor location alone are not enough to differentiate tumors of the spindle cell lipoma spectrum from other macroscopic fat-containing benign and malignant tumors, and these entities should be included in the same imaging differential diagnosis.



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Multiple skeletal muscle metastases revealing a cardiac intimal sarcoma

Abstract

We report the case of a 59-year-old female with progressive bilateral painful swelling of the thighs. MRI revealed multiple intramuscular necrotic masses with similar morphologic patterns. Whole-body CT and 18-FDG PET-CT scans demonstrated additional hypermetabolic muscular masses and a lobulated lesion within the left atrial cavity. As biopsy of a muscular mass was compatible with a poorly differentiated sarcoma with MDM2 oncogene amplification, two diagnoses were discussed: a dedifferentiated liposarcoma with muscle and heart metastases or a primary cardiac sarcoma, mainly a cardiac intimal sarcoma, with muscular metastases, which was finally confirmed by array-comparative genomic hybridization (aCGH) in a sarcoma reference center. This case emphasizes the potential for intimal sarcoma to disseminate in skeletal muscle prior to any other organ and the need for a genomic approach in addition to classical radiopathologic analyses to distinguish primary from secondary locations facing simultaneous tumors of the heart and skeletal muscles with MDM2 amplification.



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Osseous spurs at the fovea capitis femoris—a frequent finding in asymptomatic volunteers

Abstract

Objective

To investigate the different morphologic types of the fovea capitis femoris and the spectrum of osseous spurs/osteophytes of the fovea in asymptomatic volunteers and patients with hip osteoarthritis.

Material and methods

Sixty-five patients (mean age 63.6 years) with radiographically confirmed osteoarthritis of the hip and 59 asymptomatic healthy volunteers (mean age 33.9 years) underwent non-contrast MRI of the hip joint. Two radiologists independently evaluated all images. Fovea morphology (standard type, diamond type, flat type, triangular type) as well as the frequency, size and location of spurs/osteophytes of the fovea were assessed. Descriptive and inferential statistics were applied.

Results

The most frequent morphologic type of the fovea capitis femoris was the standard type for both asymptomatic volunteers (average 45%) and patients (average 49%). Osseous spurs were detected in 70% of the asymptomatic volunteers, and 97% of the patients had osteophytes. Spur size at all locations was significantly smaller in asymptomatic volunteers (range 1–2 mm) than osteophyte size in patients (range 1-4 mm) (p ≤ 0.035). In volunteers and patients, the spurs/osteophytes were most frequently located at the anterior border of the fovea capitis femoris.

Conclusion

Smaller osseous spurs (<2 mm) at the border of the fovea capitis femoris are very common in asymptomatic volunteers and do not seem to be pathologic.



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Imaging features of glenoid bare spot in a pediatric population

Abstract

Objective

The bare spot (BaS) is a central, well-circumscribed focal defect in the glenoid articular surface, with reported adult incidence of 1–2%. We aimed to reassess MRI features of BaS in the pediatric population and determine its etiology.

Materials and methods

A retrospective search of our database from June 2014 to October 2015 was performed for shoulder MRI in patients between 5 and 25 years and then subdivided into four groups: group 1, 5–10 years; group 2, 10–15 years; group 3, 15–18 years; group 4, 20–25 years. BaS was defined as a well-marginated, central defect of increased signal in the articular surface of the glenoid, seen on at least two planes, without evidence of underlying glenoid pathology. Presence, location and size along with clinical indications were documented.

Results

A final cohort of 253 patients revealed 23 BaS, 3.5% in group 1, 20% in group 2, 5% in group 3 and 4% in group 4. There was a significantly higher incidence in group 2 (p = 0.007) compared to group 3 and p = 0.002 compared to group 4. Location was mainly central. Mean size was significantly bigger in group 2 compared to group 3 and 4. Distribution showed the highest number at 14–15 years of age. Instability was higher in groups 3 and 4.

Conclusion

Incidence of BaS in group 2 was significantly higher than in other age groups and higher than in adults. BaS was also larger compared to other populations. These findings support a developmental theory, explained by the centripetal ossification of the glenoid.



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Pitfalls in soft tissue sarcoma imaging: chronic expanding hematomas

Abstract

Solid or nodular enhancement is typical of soft tissue sarcomas although high grade soft tissue sarcomas and those with internal hemorrhage often appear heterogeneous with areas of nonenhancement and solid or nodular enhancement. These MRI findings often prompt an orthopedic oncology referral, a biopsy or surgery. However, not all masses with these imaging findings are malignant. We report the multimodality imaging findings of two surgically proven chronic expanding hematomas (CEH) with imaging features that mimicked sarcomas. A third case of nonenhancing CEH of the lower extremity is also presented as a comparison. It is important that in the correct clinical scenario with typical imaging findings, the differential diagnosis of a chronic expanding hematoma be included in the workup of these patients. An image-guided biopsy of nodular tissue within such masses that proves to be negative for malignancy should not necessarily be considered discordant. A correct diagnosis may prevent a morbid unnecessary surgery and may indicate the need for a conservative noninvasive follow-up with imaging.



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Reliability of standing weight-bearing (0.25T) MR imaging findings and positional changes in the lumbar spine

Abstract

Objective

To test the reliability and absolute agreement of common degenerative findings in standing positional magnetic resonance imaging (pMRI).

Methods and materials

Low back pain patients with and without sciatica were consecutively enrolled to undergo a supine and standing pMRI. Three readers independently evaluated the standing pMRI for herniation, spinal stenosis, spondylolisthesis, HIZ lesions and facet joint effusion. The evaluation included a semi-quantitative grading of spinal stenosis, foraminal stenosis and spinal nerve root compression. The standing pMRI images were evaluated with full access to supine MRI. In case lower grades or the degenerative findings were not present in the supine images, this was reported separately as position-dependent changes. A subsample of 20 pMRI examinations was reevaluated after two months. The reproducibility was assessed by inter- and intra-reader reliability (kappa statistic) and absolute agreement between readers.

Results

Fifty-six patients were included in this study. There was fair-to-substantial inter-reader reliability (κ 0.47 to 0.82) and high absolute agreement (72.3% to 99.1%) for the pMRI findings. The intra-reader assessment showed similar reliability and agreement (κ 0.36 to 0.85; absolute agreement: 62.5% to 98.8%). Positional changes between the supine and standing position showed a fair-to-moderate inter- and intra-reader reliability (κ 0.25 to 0.52; absolute agreement: 97.0% to 99.1).

Conclusion

Evaluation of the lumbar spine for degenerative findings by standing pMRI has acceptable reproducibility; however, positional changes from the supine to the standing position as an independent outcome should be interpreted with caution because of lower reliability, which calls for further standardisation.



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Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors

Abstract

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.



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Molecular imaging in musculoskeletal infections with 99m Tc-UBI 29-41 SPECT/CT

Abstract

Objective

To determine the added value of CT over planar and SPECT-only imaging in the diagnosis of musculoskeletal infection using 99mTc-UBI 29-4.

Materials and methods

184 patients with suspected musculoskeletal infection who underwent planar and SPECT/CT imaging with 99mTc-UBI 29-41 were included. Planar, SPECT-only and SPECT/CT images were reviewed by two independent analysts for presence of bone or soft tissue infection. Final diagnosis was confirmed with tissue cultures, surgery/histology or clinical follow-up.

Results

99mTc-UBI 29-41 was true positive in 105/184 patients and true negative in 65/184 patients. When differentiating between soft tissue and bone infection, planar + SPECT-only imaging had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 95.0, 74.3, 84.8, 91.3 and 86.9%, respectively, versus 99.0, 94.5, 92.5, 98.5 and 94.5% for SPECT/CT. SPECT/CT resulted in a change in reviewers' confidence in the final diagnosis in 91/184 patients. Inter-observer agreement was better with SPECT/CT compared with planar + SPECT imaging (kappa 0.87, 95% CI 0.71–0.85 versus kappa 0.81, 95% CI 0.58–0.75).

Conclusion

Addition of CT to planar and SPECT-only imaging led to an increase in diagnostic performance and an improvement in reviewers' confidence and inter-observer agreement in differentiating bone from soft tissue infection.



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Clinical decision support of radiotherapy treatment planning: A data-driven machine learning strategy for patient-specific dosimetric decision making

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Publication date: Available online 20 November 2017
Source:Radiotherapy and Oncology
Author(s): Gilmer Valdes, Charles B. Simone, Josephine Chen, Alexander Lin, Sue S. Yom, Adam J. Pattison, Colin M. Carpenter, Timothy D. Solberg
Background and purposeClinical decision support systems are a growing class of tools with the potential to impact healthcare. This study investigates the construction of a decision support system through which clinicians can efficiently identify which previously approved historical treatment plans are achievable for a new patient to aid in selection of therapy.Material and methodsTreatment data were collected for early-stage lung and postoperative oropharyngeal cancers treated using photon (lung and head and neck) and proton (head and neck) radiotherapy. Machine-learning classifiers were constructed using patient-specific feature-sets and a library of historical plans. Model accuracy was analyzed using learning curves, and historical treatment plan matching was investigated.ResultsLearning curves demonstrate that for these datasets, approximately 45, 60, and 30 patients are needed for a sufficiently accurate classification model for radiotherapy for early-stage lung, postoperative oropharyngeal photon, and postoperative oropharyngeal proton, respectively. The resulting classification model provides a database of previously approved treatment plans that are achievable for a new patient. An exemplary case, highlighting tradeoffs between the heart and chest wall dose while holding target dose constant in two historical plans is provided.ConclusionsWe report on the first artificial-intelligence based clinical decision support system that connects patients to past discrete treatment plans in radiation oncology and demonstrate for the first time how this tool can enable clinicians to use past decisions to help inform current assessments. Clinicians can be informed of dose tradeoffs between critical structures early in the treatment process, enabling more time spent on finding the optimal course of treatment for individual patients.



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Short interactive workshops reduce variability in contouring treatment volumes for spine stereotactic body radiation therapy: Experience with the ESTRO FALCON programme and EduCase™ training tool

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Publication date: Available online 20 November 2017
Source:Radiotherapy and Oncology
Author(s): Berardino De Bari, Max Dahele, Miika Palmu, Scott Kaylor, Luis Schiappacasse, Matthias Guckenberger
We report the results of 4, 2-h contouring workshops on target volume definition for spinal stereotactic radiotherapy. They combined traditional teaching methods with a web-based contouring/contour-analysis platform and led to a significant reduction in delineation variability. Short, interactive workshops can reduce interobserver variability in spine SBRT target volume delineation.



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Effect of Shift, Schedule, and Volume on Interpretive Accuracy: A Retrospective Analysis of 2.9 Million Radiologic Examinations.

Effect of Shift, Schedule, and Volume on Interpretive Accuracy: A Retrospective Analysis of 2.9 Million Radiologic Examinations.

Radiology. 2017 Nov 20;:170555

Authors: Hanna TN, Lamoureux C, Krupinski EA, Weber S, Johnson JO

Abstract
Purpose To determine whether there is an association between radiologist shift length, schedule, or examination volume and interpretive accuracy. Materials and Methods This study was institutional review board approved and HIPAA compliant. A retrospective analysis of all major discrepancies from a 2015 quality assurance database of a teleradiology practice was performed. Board-certified radiologists provided initial preliminary interpretations. Discrepancies were identified during a secondary review by a practicing radiologist or through an internal quality assurance process and were vetted through a consensus radiology quality assurance committee. Unique anonymous radiologist identifiers were used to link the discrepancies to radiologists' shifts and schedules. Data were analyzed by using analysis of variance, t test, or χ(2) test. Results A total of 4294 major discrepancies resulted from 2 922 377 examinations (0.15%). There was a significant difference for shift length (P < .0001) and volume (P < .0001) for shifts with versus those without discrepancies. On average, errors occurred a mean (± standard deviation) of 8.97 hours ± 2.28 into the shift (median, 10 hours; interquartile range, 2.0 hours). Significantly more errors occurred late in shifts than early (P < .0001), peaking between 10 and 12 hours. The number of major discrepancies in a single shift ranged from one to four, with a significant difference in the number of discrepancies as a function of study volume (volume for all shifts, 67.60 ± 60.24; volume for shifts with major discrepancies, 118.96 ± 66.89; P < .001). Despite a trend for more discrepancies after more consecutive days worked, the difference was not significant (P = .0893). Conclusion Longer shifts and higher diagnostic examination volumes are associated with increased major interpretive discrepancies. These are more likely to occur later in a shift, peaking after the 10th hour of work. (©) RSNA, 2017.

PMID: 29156150 [PubMed - as supplied by publisher]



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Quantitative Evaluation of Vertebral Microvascular Permeability and Fat Fraction in Alloxan-induced Diabetic Rabbits.

Quantitative Evaluation of Vertebral Microvascular Permeability and Fat Fraction in Alloxan-induced Diabetic Rabbits.

Radiology. 2017 Nov 20;:170760

Authors: Hu L, Zha YF, Wang L, Li L, Xing D, Gong W, Wang J, Lin Y, Zeng FF, Lu XS

Abstract
Purpose To determine longitudinal relationships between lumbar vertebral bone marrow permeability and marrow adipose tissue in a rabbit diabetes model by using quantitative dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging and iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL IQ) sequence. Materials and Methods Twenty rabbits were randomly assigned to the diabetic (n = 10) or control (n = 10) group. All rabbits underwent sagittal MR imaging of the lumbar region at fixed time points (0, 4, 8, 12, and 16 weeks after alloxan injection). A linear mixed-effects model was used to analyze fat fraction (FF) and permeability parameter changes for 16 months after baseline. These parameters were compared between the two groups by using an independent-samples t test. Correlation of DCE MR imaging parameters with FF and with microvessel density (MVD) was analyzed by using the Spearman correlation coefficient. All statistical analyses were performed with software. Results Twelve weeks after injection, transfer constant (K(trans)) and rate constant (Kep) were markedly and significantly increased, while fractional plasma volume (Vp) significantly decreased. The volume of extravascular extracellular space (Ve) decreased significantly after 16 weeks in the diabetic group. MVD was negatively correlated with K(trans) and Kep and positively correlated with Ve and Vp, while FF was positively correlated with K(trans) and Kep and negatively correlated with Ve and Vp (P < .05 for all). Conclusion DCE MR imaging and the IDEAL IQ sequence can be used for quantitative evaluation of changes in vertebral microvascular permeability and vertebral fat deposition in alloxan-induced diabetic rabbits. This variation is highly associated with increased vertebral fat deposition. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29156149 [PubMed - as supplied by publisher]



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CM-101: Type I Collagen-targeted MR Imaging Probe for Detection of Liver Fibrosis.

CM-101: Type I Collagen-targeted MR Imaging Probe for Detection of Liver Fibrosis.

Radiology. 2017 Nov 20;:170595

Authors: Farrar CT, Gale EM, Kennan R, Ramsay I, Masia R, Arora G, Looby K, Wei L, Kalpathy-Cramer J, Bunzel MM, Zhang C, Zhu Y, Akiyama TE, Klimas M, Pinto S, Diyabalanage H, Tanabe KK, Humblet V, Fuchs BC, Caravan P

Abstract
Purpose To evaluate the biodistribution, metabolism, and pharmacokinetics of a new type I collagen-targeted magnetic resonance (MR) probe, CM-101, and to assess its ability to help quantify liver fibrosis in animal models. Materials and Methods Biodistribution, pharmacokinetics, and stability of CM-101 in rats were measured with mass spectrometry. Bile duct-ligated (BDL) and sham-treated rats were imaged 19 days after the procedure by using a 1.5-T clinical MR imaging unit. Mice were treated with carbon tetrachloride (CCl4) or with vehicle two times a week for 10 weeks and were imaged with a 7.0-T preclinical MR imaging unit at baseline and 1 week after the last CCl4 treatment. Animals were imaged before and after injection of 10 µmol/kg CM-101. Change in contrast-to-noise ratio (ΔCNR) between liver and muscle tissue after CM-101 injection was used to quantify liver fibrosis. Liver tissue was analyzed for Sirius Red staining and hydroxyproline content. The institutional subcommittee for research animal care approved all in vivo procedures. Results CM-101 demonstrated rapid blood clearance (half-life = 6.8 minutes ± 2.4) and predominately renal elimination in rats. Biodistribution showed low tissue gadolinium levels at 24 hours (<3.9% injected dose [ID]/g ± 0.6) and 10-fold lower levels at 14 days (<0.33% ID/g ± 12) after CM-101 injection with negligible accumulation in bone (0.07% ID/g ± 0.02 and 0.010% ID/g ± 0.004 at 1 and 14 days, respectively). ΔCNR was significantly (P < .001) higher in BDL rats (13.6 ± 3.2) than in sham-treated rats (5.7 ± 4.2) and in the CCl4-treated mice (18.3 ± 6.5) compared with baseline values (5.2 ± 1.0). Conclusion CM-101 demonstrated fast blood clearance and whole-body elimination, negligible accumulation of gadolinium in bone or tissue, and robust detection of fibrosis in rat BDL and mouse CCl4 models of liver fibrosis. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29156148 [PubMed - as supplied by publisher]



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Electromagnetic Navigational Bronchoscopy versus CT-guided Percutaneous Sampling of Peripheral Indeterminate Pulmonary Nodules: A Cohort Study.

Electromagnetic Navigational Bronchoscopy versus CT-guided Percutaneous Sampling of Peripheral Indeterminate Pulmonary Nodules: A Cohort Study.

Radiology. 2017 Nov 20;:170893

Authors: Bhatt KM, Tandon YK, Graham R, Lau CT, Lempel JK, Azok JT, Mazzone PJ, Schneider E, Obuchowski NA, Bolen MA

Abstract
Purpose To compare the diagnostic yield and complication rates of electromagnetic navigational bronchoscopic (ENB)-guided and computed tomography (CT)-guided percutaneous tissue sampling of lung nodules. Materials and Methods Retrospectively identified were 149 patients sampled percutaneously with CT guidance and 146 patients who underwent ENB with transbronchial biopsy of a lung lesion between 2013 and 2015. Clinical data, incidence of complications, and nodule pathologic analyses were assessed through electronic medical record review. Lung nodule characteristics were reviewed through direct image analysis. Molecular marker studies and pathologic analyses from surgical excision were reviewed when available. Multiple-variable logistic regression models were built to compare the diagnostic yield and complication rates for each method and for different patient and disease characteristics. Results CT-guided sampling was more likely to be diagnostic than ENB-guided biopsy (86.0% [129 of 150] vs 66.0% [99 of 150], respectively), and this difference remained significant even after adjustments were made for patient and nodule characteristics (P < .001). Age, American Society of Anesthesiologists class, emphysema grade, nodule size, and distance from pleura were not significant predictors of increased diagnostic yield. Intraprocedural time for physicians was significantly lower with CT-guided sampling (P < .001). Similar yield for molecular analyses was noted with the two approaches (ENB-guided sampling, 88.9% [32 of 36]; CT-guided sampling, 82.0% [41 of 50]). The two groups had similar rates of major complications (symptomatic hemorrhage, P > .999; pneumothorax requiring chest tube and/or admission, P = .417). Conclusion CT-guided transthoracic biopsy provided higher diagnostic yield in the assessment of peripheral pulmonary nodules than navigational bronchoscopy with a similar rate of clinically relevant complications. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29156147 [PubMed - as supplied by publisher]



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Effectiveness of a Staged US and Unenhanced MR Imaging Algorithm in the Diagnosis of Pediatric Appendicitis.

Effectiveness of a Staged US and Unenhanced MR Imaging Algorithm in the Diagnosis of Pediatric Appendicitis.

Radiology. 2017 Nov 20;:162755

Authors: Dibble EH, Swenson DW, Cartagena C, Baird GL, Herliczek TW

Abstract
Purpose To establish, in a large cohort, the diagnostic performance of a staged algorithm involving ultrasonography (US) followed by conditional unenhanced magnetic resonance (MR) imaging for the imaging work-up of pediatric appendicitis. Materials and Methods A staged imaging algorithm in which US and unenhanced MR imaging were performed in pediatric patients suspected of having appendicitis was implemented at the authors' institution on January 1, 2011, with US as the initial modality followed by unenhanced MR imaging when US findings were equivocal. A search of the radiology database revealed 2180 pediatric patients who had undergone imaging for suspected appendicitis from January 1, 2011, through December 31, 2012. Of the 2180 patients, 1982 (90.9%) were evaluated according to the algorithm. The authors reviewed the electronic medical records and imaging reports for all patients. Imaging reports were reviewed and classified as positive, negative, or equivocal for appendicitis and correlated with surgical and pathology reports. Results The frequency of appendicitis was 20.5% (407 of 1982 patients). US alone was performed in 1905 of the 1982 patients (96.1%), yielding a sensitivity of 98.7% (386 of 391 patients) and specificity of 97.1% (1470 of 1514 patients) for appendicitis. Seventy-seven patients underwent unenhanced MR imaging after equivocal US findings, yielding an overall algorithm sensitivity of 98.2% (400 of 407 patients) and specificity of 97.1% (1530 of 1575 patients). Seven of the 1982 patients (0.4%) had false-negative results with the staged algorithm. The negative predictive value of the staged algorithm was 99.5% (1530 of 1537 patients). Conclusion A staged algorithm of US and unenhanced MR imaging for pediatric appendicitis appears to be effective. The results of this study demonstrate that this staged algorithm is 98.2% sensitive and 97.1% specific for the diagnosis of appendicitis in pediatric patients. (©) RSNA, 2017.

PMID: 29156146 [PubMed - as supplied by publisher]



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Fractional Flow Reserve Estimated at Coronary CT Angiography in Intermediate Lesions: Comparison of Diagnostic Accuracy of Different Methods to Determine Coronary Flow Distribution.

Fractional Flow Reserve Estimated at Coronary CT Angiography in Intermediate Lesions: Comparison of Diagnostic Accuracy of Different Methods to Determine Coronary Flow Distribution.

Radiology. 2017 Nov 20;:162620

Authors: Kishi S, Giannopoulos AA, Tang A, Kato N, Chatzizisis YS, Dennie C, Horiuchi Y, Tanabe K, Lima JAC, Rybicki FJ, Mitsouras D

Abstract
Purpose To compare the diagnostic accuracy of different computed tomographic (CT) fractional flow reserve (FFR) algorithms for vessels with intermediate stenosis. Materials and Methods This cross-sectional HIPAA-compliant and human research committee-approved study applied a four-step CT FFR algorithm in 61 patients (mean age, 69 years ± 10; age range, 29-89 years) with a lesion of intermediate-diameter stenosis (25%-69%) at CT angiography who underwent FFR measurement within 90 days. The per-lesion diagnostic performance of CT FFR was tested for three different approaches to estimate blood flow distribution for CT FFR calculation. The first two, the Murray law and the Huo-Kassab rule, used coronary anatomy; the third used contrast material opacification gradients. CT FFR algorithms and CT angiography percentage diameter stenosis (DS) measurements were compared by using the area under the receiver operating characteristic curve (AUC) to detect FFRs of 0.8 or lower. Results Twenty-five lesions (41%) had FFRs of 0.8 or lower. The AUC of CT FFR determination by using contrast material gradients (AUC = 0.953) was significantly higher than that of the Huo-Kassab (AUC = 0.882, P = .043) and Murray law models (AUC = 0.871, P = .033). All three AUCs were higher than that for 50% or greater DS at CT angiography (AUC = 0.596, P < .001). Correlation of CT FFR with FFR was highest for gradients (Spearman ρ = 0.80), followed by the Huo-Kassab rule (ρ = 0.68) and Murray law (ρ = 0.67) models. All CT FFR algorithms had small biases, ranging from -0.015 (Murray) to -0.049 (Huo-Kassab). Limits of agreement were narrowest for gradients (-0.182, 0.147), followed by the Huo-Kassab rule (-0.246, 0.149) and the Murray law (-0.285, 0.256) models. Conclusion Clinicians can perform CT FFR by using a four-step approach on site to accurately detect hemodynamically significant intermediate-stenosis lesions. Estimating blood flow distribution by using coronary contrast opacification variations may improve CT FFR accuracy. (©) RSNA, 2017 Online supplemental material is available for this article.

PMID: 29156145 [PubMed - as supplied by publisher]



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From Images to Actions: Opportunities for Artificial Intelligence in Radiology.

From Images to Actions: Opportunities for Artificial Intelligence in Radiology.

Radiology. 2017 Dec;285(3):719-720

Authors: Kahn CE

PMID: 29155645 [PubMed - in process]



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Radiogenomics Map: A Novel Approach for Noninvasive Identification of Molecular Properties?

Radiogenomics Map: A Novel Approach for Noninvasive Identification of Molecular Properties?

Radiology. 2017 Dec;285(3):1060-1061

Authors: Chen S, Ning Z, He X, Qi X

PMID: 29155644 [PubMed - in process]



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Structural and Functional Network Dysfunction in Parkinson Disease.

Structural and Functional Network Dysfunction in Parkinson Disease.

Radiology. 2017 Dec;285(3):725-727

Authors: Herrington TM, Briscoe J, Eskandar E

PMID: 29155643 [PubMed - in process]



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Extracting Regional Oxygen Tension from Multibreath Wash-in (3)He MR Imaging.

Extracting Regional Oxygen Tension from Multibreath Wash-in (3)He MR Imaging.

Radiology. 2017 Dec;285(3):1056-1057

Authors: Möller HE

PMID: 29155642 [PubMed - in process]



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Pulsed Focused Ultrasound Stimulates the Release of Tumor Biomarkers into the Blood Circulation.

Pulsed Focused Ultrasound Stimulates the Release of Tumor Biomarkers into the Blood Circulation.

Radiology. 2017 Dec;285(3):1058-1060

Authors: Pan H, Zhou W, Wang S

PMID: 29155641 [PubMed - in process]



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Recurrence of Renal Cell Cancers after Thermal Ablation.

Recurrence of Renal Cell Cancers after Thermal Ablation.

Radiology. 2017 Dec;285(3):1061-1063

Authors: Bai Y

PMID: 29155640 [PubMed - in process]



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When Machines Think: Radiology's Next Frontier.

When Machines Think: Radiology's Next Frontier.

Radiology. 2017 Dec;285(3):713-718

Authors: Dreyer KJ, Geis JR

Abstract
Artificial intelligence (AI), machine learning, and deep learning are terms now seen frequently, all of which refer to computer algorithms that change as they are exposed to more data. Many of these algorithms are surprisingly good at recognizing objects in images. The combination of large amounts of machine-consumable digital data, increased and cheaper computing power, and increasingly sophisticated statistical models combine to enable machines to find patterns in data in ways that are not only cost-effective but also potentially beyond humans' abilities. Building an AI algorithm can be surprisingly easy. Understanding the associated data structures and statistics, on the other hand, is often difficult and obscure. Converting the algorithm into a sophisticated product that works consistently in broad, general clinical use is complex and incompletely understood. To show how these AI products reduce costs and improve outcomes will require clinical translation and industrial-grade integration into routine workflow. Radiology has the chance to leverage AI to become a center of intelligently aggregated, quantitative, diagnostic information. Centaur radiologists, formed as a synergy of human plus computer, will provide interpretations using data extracted from images by humans and image-analysis computer algorithms, as well as the electronic health record, genomics, and other disparate sources. These interpretations will form the foundation of precision health care, or care customized to an individual patient. (©) RSNA, 2017.

PMID: 29155639 [PubMed - in process]



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2017: A Look Back.

2017: A Look Back.

Radiology. 2017 Dec;285(3):702-704

Authors: Kressel HY

PMID: 29155638 [PubMed - in process]



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2017 Manuscript Reviewers: A Note of Thanks.

2017 Manuscript Reviewers: A Note of Thanks.

Radiology. 2017 Dec;285(3):705-711

Authors: Ehman RL, Kressel HY

PMID: 29155637 [PubMed - in process]



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Hepatic Imaging in Neonates and Young Infants: State of the Art.

Hepatic Imaging in Neonates and Young Infants: State of the Art.

Radiology. 2017 Dec;285(3):763-777

Authors: Shamir SB, Kurian J, Kogan-Liberman D, Taragin BH

Abstract
Neonatal liver disease is an important source of morbidity in the pediatric population. The manifestation of liver disease in young infants may be different than in older patients, and there are a number of diagnoses that are unique to this age group. Familiarity with these entities is important as imaging plays a key role in the diagnostic workup, and prompt diagnosis is necessary to prevent complications. This article reviews the spectrum of liver pathologies that can manifest in the first 6 months of life and is intended to educate the general radiologist who may be faced with interpretation of neonatal liver imaging. Categories of disease that will be reviewed include cholestatic diseases, tumors, vascular anomalies, and acquired diseases. The authors will also review optimization of ultrasonography (US) and magnetic resonance imaging of the liver and present a systematic method for interpretation of neonatal liver US findings in the context of clinical and laboratory findings. (©) RSNA, 2017.

PMID: 29155636 [PubMed - in process]



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Case 248: Cystic Duodenal Dystrophy with Groove Pancreatitis.

Case 248: Cystic Duodenal Dystrophy with Groove Pancreatitis.

Radiology. 2017 Dec;285(3):1045-1051

Authors: Patil AR, Nandikoor S, Mallarajapatna G, Shivakumar S

Abstract
History A 59-year-old man presented to the gastroenterology outpatient department with acute abdominal pain centered in the epigastrium. He had experienced similar episodes of abdominal pain in the past that had been treated with surgery. He reported multiple failed attempts at upper gastrointestinal endoscopy. Laboratory tests were performed at the time of admission and revealed a serum glutamic-oxaloacetic transaminase level of 9 U/L [0.15 μkat/L] (normal range, 5-40 U/L [0.08-0.67 μkat/L]), a serum glutamic-pyruvic transaminase level of 34 U/L [0.57 μkat/L] (normal range, 5-45 U/L [0.08-0.75 μkat/L]), a serum γ-glutamyltransferase level of 210 U/L (3.50 μkat/L) (normal range, 10-50 U/L [0.17-0.83 μkat/L]), a serum alkaline phosphatase level of 157 U/L (2.62 μkat/L) (normal range, 30-120 U/L [0.50-2.0 μkat/L]), a serum amylase level of 210 U/L (3.50 μkat/L) (normal range, 30-100 U/L [0.50-1.66 μkat/L]), a serum lipase level of 391 U/L (6.52 μkat/L) (normal range, 13-60 U/L [0.21-1.0 μkat/L]), an α-fetoprotein level of 3.81 ng/ mL (normal range, 0-9 ng/mL), a total protein level of 4.6 g/dL (normal range, 6.0-8.5 g/dL), and an albumin level of 2.6 g/dL (normal range, 3.5-5.2 g/dL). The rest of the laboratory data were unremarkable. The patient underwent erect abdominal radiography, contrast material-enhanced multidetector row computed tomography (CT) of the abdomen with 100 mL of iohexol (300 mg iodine per milliliter, Omnipaque; GE Healthcare, Shanghai, China) followed by combined positron emission tomography (PET) and CT (hereafter, PET/CT) with 6.9 mCi of fluorodeoxyglucose (FDG) and magnetic resonance (MR) imaging of the upper abdomen.

PMID: 29155635 [PubMed - in process]



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How Does Imaging of Congenital Zika Compare with Imaging of Other TORCH Infections?

How Does Imaging of Congenital Zika Compare with Imaging of Other TORCH Infections?

Radiology. 2017 Dec;285(3):744-761

Authors: Levine D, Jani JC, Castro-Aragon I, Cannie M

Abstract
The acronym TORCH is used to refer to congenital infections, such as toxoplasmosis, other infections (such as syphillis, varicella-zoster, and parvovirus B19), cytomegalovirus, and herpes simplex virus. The classic findings in patients with TORCH infections include rash in the mother during pregnancy and ocular findings in the newborn. Zika virus has emerged as an important worldwide congenital infection. It fits well with other congenital TORCH infections since there is a rash in the mother and there are commonly ocular abnormalities in the newborn. TORCH infections are recognized to have neurologic effects, such as ventriculomegaly, intraventricular adhesions, subependymal cysts, intracerebral calcifications, and microcephaly; however, the Zika virus is intensely neurotropic. Thus, it targets neural progenitor cells, leading to a more severe spectrum of central nervous system abnormalities than is typically seen in other TORCH infections, while relatively sparing the other organ systems. In this review, nonspecific findings of congenital infections initially will be described, then individual TORCH infections will be described and compared with the imaging findings associated with congenital Zika virus infection. For the radiologist, awareness of imaging features of common congenital infections may facilitate early diagnosis and may, at times, lead to prompt initiation of therapy. Online supplemental material is available for this article.

PMID: 29155634 [PubMed - in process]



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Robert McLelland, MD.

Robert McLelland, MD.

Radiology. 2017 Dec;285(3):1066

Authors: Pisano E

PMID: 29155633 [PubMed - in process]



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Regional Fractional Ventilation by Using Multibreath Wash-in (3)He MR Imaging.

Regional Fractional Ventilation by Using Multibreath Wash-in (3)He MR Imaging.

Radiology. 2017 Dec;285(3):1063

Authors: Hamedani H, Clapp JT, Kadlecek SJ, Emami K, Ishii M, Gefter WB, Xin Y, Cereda M, Shaghaghi H, Siddiqui S, Rossman MD, Rizi RR

PMID: 29155632 [PubMed - in process]



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Minimum unit pricing for alcohol clears final legal hurdle in Scotland

Scotland’s journey to a minimum unit price for alcohol has taken 10 years. It can be traced to a 2007 report by SHAAP, the coalition of Scottish Medical Royal Colleges and Faculties.1 The Scottish...
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Povidone iodine versus silver nitrate in induction of sclerosing cholangitis in hepatic hydatid cysts surgery

Abstract

There are several scolicidal agents for inactivation of hydatid cyst protoscolices during surgery, but most of them are associated with adverse side effects such as sclerosing cholangitis and liver necrosis. The present study aims to evaluate the adverse effects of povidone iodine versus silver nitrate in producing sclerosing cholangitis in animal model. Twenty guinea pigs weighing 250–350 g were used in this study. In one group, 0.3 ml 10% povidone iodine was used for 5 min in the biliary tree while in the second group, 0.3 ml 0.5% silver nitrate was used for the same amount of time. After 4 months, the animals were euthanized, and the livers, common bile ducts, and duodenums were resected and immediately sent for cholangiographic studies. Eight animals showed sclerosing cholangitis in the povidone iodine group (80%), whereas only two showed (20%) sclerosing cholangitis in the silver nitrate group. The difference between the two groups was statistically significant. There was a significant risk of sclerosing cholangitis after administration of 10% povidone iodine as a protoscolicidal agent.



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Bilateral Testicular Infarction from IgA Vasculitis of the Spermatic Cords

A 51-year-old man with type 2 diabetes mellitus and chronic obstructive pulmonary disease presented to the emergency room with increasing bilateral leg pain, rash, and scrotal swelling with pain. Skin biopsy from his thigh revealed IgA-associated vasculitis. Due to hematuria, a renal biopsy was performed and showed an IgA glomerulonephritis with focal fibrinoid necrosis and neutrophil accumulation. Bilateral orchiectomies were performed in two separate procedures ten and thirteen days after the renal biopsy, as a result of uncontrolled abscess formation in testicles. Microscopically, both testicles revealed large abscess formation destroying almost the entire testicular parenchyma without tumor cells. Spermatic cord margins were further scrutinized microscopically to show bilateral vasculitis in many small size vessels, confirmed by positive endothelial staining for IgA. Some of the affected arteries revealed central organizing thrombi with recanalization features, highly suggestive of vasculitis-associated thrombi formation, resulting in testicular ischemic infarction and abscess formation. We conclude that this adult patient developed a severe form of Henoch-Schönlein purpura, with vasculitis affecting multiple organs, including the most serious and unusual complication of bilateral testicular infarction.

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Prospective Validation of the Decalogue, a Set of Doctor-Patient Communication Recommendations to Improve Patient Illness Experience and Mood States within a Hospital Cardiologic Ambulatory Setting

Strategies to improve doctor-patient communication may have a beneficial impact on patient’s illness experience and mood, with potential favorable clinical effects. We prospectively tested the psychometric and clinical validity of the Decalogue, a tool utilizing 10 communication recommendations for patients and physicians. The Decalogue was administered to 100 consecutive patients referred for a cardiologic consultation, whereas 49 patients served as controls. The POMS-2 questionnaire was used to measure the total mood disturbance at the end of the consultation. Structural equation modeling showed high internal consistency (Cronbach alpha 0.93), good test-retest reproducibility, and high validity of the psychometric construct (all > 0.80), suggesting a positive effect on patients’ illness experience. The total mood disturbance was lower in the patients exposed to the Decalogue as compared to the controls ( versus , ). In an additional questionnaire, patients in the Decalogue group showed a trend towards a better understanding of their state of health (). In a cardiologic ambulatory setting, the Decalogue shows good validity and reliability as a tool to improve patients’ illness experience and could have a favorable impact on mood states. These effects might potentially improve patient engagement in care and adherence to therapy, as well as clinical outcome.

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Compound Wumei Powder Inhibits the Invasion and Metastasis of Gastric Cancer via Cox-2/PGE2-PI3K/AKT/GSK3β/β-Catenin Signaling Pathway

To explore the role of CWP in invasion and migration of gastric cancer cells and its underlying molecular mechanism, we performed the experiment in SGC-7901 cells both in vitro and in vivo. In the cell experiment, we evaluated cell proliferation by MTT assay. The results showed that CWP can inhibit the growth of SGC-7901 cells. The influence on cell migration and invasion was detected by wound-healing and Transwell invasion assays. The results showed that the abilities of invasion and migration are restrained in CWP group. Western blot showed that CWP can decrease the expression of Cox-2 and inhibit the PI3K/AKT/GSK3β/β-catenin signaling pathway. In the animal experiment, we observed that CWP had an inhibitory effect on the growth of xenograft tumors of nude mice. IHC assay, ELISA, RT-PCR assay, and Western blot assay were used to test relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3β/β-catenin pathway. The results showed that CWP can suppress relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3β/β-catenin pathway. In conclusion, we suggest that CWP inhibits the invasion and metastasis of SGC-7901 cells via Cox-2/PGE2-PI3K/AKT/GSK3β/β-catenin signaling pathway.

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Facilitation of Vaginal Delivery in an Infant with Complete Heart Block Secondary to Maternal Anti-Ro Antibodies

Congenital heart block (CHB) is a rare disorder that may be associated with a high morbidity and even mortality, with a risk of death both in utero and during infancy. Women with serum titres of anti-Ro and/or anti-La antibodies carry a risk of CHB of 1–5% in their offspring, with a recurrence risk of approximately 20%. We present a case of a 36-year-old female with a pregnancy complicated by congenital heart block. Autoimmune profiling at booking showed she was positive for lupus anticoagulant and anti-Ro antibodies. A fetal echocardiogram at 21 + 3 showed complete heart block. She was monitored throughout the remainder of her pregnancy with serial growth scans, cardiovascular profiling, and BPP scoring. She had a normal vaginal delivery at term to a female infant.

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The Bioinformatic Analysis of the Dysregulated Genes and MicroRNAs in Entorhinal Cortex, Hippocampus, and Blood for Alzheimer’s Disease

Aim. The incidence of Alzheimer’s disease (AD) has been increasing in recent years, but there exists no cure and the pathological mechanisms are not fully understood. This study aimed to find out the pathogenesis of learning and memory impairment, new biomarkers, potential therapeutic targets, and drugs for AD. Methods. We downloaded the microarray data of entorhinal cortex (EC) and hippocampus (HIP) of AD and controls from Gene Expression Omnibus (GEO) database, and then the differentially expressed genes (DEGs) in EC and HIP regions were analyzed for functional and pathway enrichment. Furthermore, we utilized the DEGs to construct coexpression networks to identify hub genes and discover the small molecules which were capable of reversing the gene expression profile of AD. Finally, we also analyzed microarray and RNA-seq dataset of blood samples to find the biomarkers related to gene expression in brain. Results. We found some functional hub genes, such as ErbB2, ErbB4, OCT3, MIF, CDK13, and GPI. According to GO and KEGG pathway enrichment, several pathways were significantly dysregulated in EC and HIP. CTSD and VCAM1 were dysregulated significantly in blood, EC, and HIP, which were potential biomarkers for AD. Target genes of four microRNAs had similar GO_terms distribution with DEGs in EC and HIP. In addtion, small molecules were screened out for AD treatment. Conclusion. These biological pathways and DEGs or hub genes will be useful to elucidate AD pathogenesis and identify novel biomarkers or drug targets for developing improved diagnostics and therapeutics against AD.

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Development of an Analytical Protocol for Determination of Cyanide in Human Biological Samples Based on Application of Ion Chromatography with Pulsed Amperometric Detection

A simple and accurate ion chromatography (IC) method with pulsed amperometric detection (PAD) was proposed for the determination of cyanide ion in urine, sweat, and saliva samples. The sample pretreatment relies on alkaline digestion and application of Dionex OnGuard II H cartridge. Under the optimized conditions, the method showed good linearity in the range of 1–100 μg/L for urine, 5–100 μg/L for saliva, and 3–100 μg/L for sweat samples with determination coefficients . Low detection limits (LODs) in the range of 1.8 μg/L, 5.1 μg/L, and 5.8 μg/L for urine, saliva, and sweat samples, respectively, and good repeatability (CV

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Computational Design Scheme for Wind Turbine Drive-Train Based on Lagrange Multipliers

The design optimization of wind turbines and their subsystems will make them competitive as an ideal alternative for energy. This paper proposed a design procedure for one of these subsystems, which is the Wind Turbine Drive-Train (WTDT). The design of the WTDT is based on the load assumptions and considered as the most significant parameter for increasing the efficiency of energy generation. In industry, these loads are supplemented by expert assumptions and manipulated to design the transmission elements. In contrary, in this work, the multibody system approach is used to estimate the static as well as dynamic loads based on the Lagrange multipliers. Lagrange multipliers are numerical parameters associated with the holonomic and nonholonomic constraints assigned in the drive-train model. The proposed scheme includes computational manipulations of kinematic constraints, mapping the generalized forces into Cartesian respective, and enactment of velocity-based constrains. Based on the dynamic model and the obtained forces, the design process of a planetary stage of WTDT is implemented with trade-off’s optimization in terms of gearing parameters. A wind turbine of 1.4 megawatts is introduced as an evaluation study of the proposed procedure, in which the main advantage is the systematic nature of designing complex systems in motion.

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Nontrivial Solution for the Fractional -Laplacian Equations via Perturbation Methods

We study the existence of nontrivial solution of the following equation without compactness: ,   where ,  ,   is the fractional -Laplacian, and the subcritical -superlinear term is 1-periodic in for . Our main difficulty is that the weak limit of (PS) sequence is not always the weak solution of fractional -Laplacian type equation. To overcome this difficulty, by adding coercive potential term and using mountain pass theorem, we get the weak solution of perturbation equations. And we prove that as . Finally, by using vanishing lemma and periodic condition, we get that is a nontrivial solution of fractional -Laplacian equation.

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Contents Vol. 82, 2016


Hum Hered 2016;82:I-II

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The exquisite marble that sculptor Michelangelo couldn’t use

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Workers at the Cervaiole quarry have supplied marble to Auguste Rodin and Henry Moore. But the beautiful rock was discovered 500 years ago by Michelangelo

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We got a good look at the interstellar asteroid and it’s weird

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Our first detailed glimpse at ‘Oumuamua, the interstellar asteroid that recently flew by Earth, shows it’s one of the weirdest asteroids we’ve ever seen

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More or less likely to offend? Young adults with a history of identified developmental language disorders

Abstract

Background

There is now substantial literature demonstrating that a disproportionate number of young people who come into contact with youth justice services evidence unidentified language difficulties. These young people, therefore, have received little or no professional input in this area. Conversely, there is a dearth of research pertaining to criminality outcomes among those individuals with identified developmental language disorders (DLD) who have received such interventions.

Aims

To examine police-initiated contact and substance use outcomes of young adults with a history of identified DLD versus age-matched peers (AMP). Additionally, self-reported rule breaking behaviours and aggression are considered. We hypothesize that early identification/intervention reduces engagement with risky behaviour such as substance and alcohol use as well as offending-related behaviours.

Methods & Procedures

Adversarial police-initiated contacts were examined in 84 young adults with a history of DLD and 88 AMP. Rule-breaking and aggression were evaluated using the Achenbach Adult Self-Report for ages 18–59 years.

Outcomes & Results

Adults with a history of DLD who received targeted intervention during their school years reported less contact with their local police service compared with AMPs at age 24. Comparable proportions of both groups reported current alcohol consumption, but group differences were found relating to alcohol use. No group differences in rule-breaking behaviours were found, but the DLD group was found to have a statistically significant higher raw score on the aggressive behaviour scale.

Conclusions & Implications

There is a need for early identification of children with DLD. Early intervention aimed at ameliorating such difficulties could possibly have distal outcomes in relation to offending.



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Speech deterioration in amyotrophic lateral sclerosis (ALS) after manifestation of bulbar symptoms

Abstract

Background

The symptoms and their progression in amyotrophic lateral sclerosis (ALS) are typically studied after the diagnosis has been confirmed. However, many people with ALS already have severe dysarthria and loss of adequate speech at the time of diagnosis. Speech-and-language therapy interventions should be targeted timely based on communicative need in ALS.

Aims

To investigate how long natural speech will remain functional and to identify the changes in the speech of persons with ALS.

Methods & Procedures

Altogether 30 consecutive participants were studied and divided into two groups based on the initial type of ALS, bulbar or spinal. Their speech disorder was evaluated on severity, articulation rate and intelligibility during the 2-year follow-up.

Outcome & Results

The ability to speak deteriorated to poor and necessitated augmentative and alternative communication (AAC) methods with 60% of the participants. Their speech remained adequate on average for 18 months from the first bulbar symptom. Severity, articulation rate and intelligibility declined with nearly all participants during the study. To begin with speech deteriorated more in the bulbar group than in the spinal group and the difference remained during the whole follow-up with some exceptions.

Conclusions & Implications

The onset of bulbar symptoms indicated the time to loss of speech better than when assessed from ALS diagnosis or the first speech therapy evaluation. In clinical work, it is important to take the initial type of ALS into consideration when determining the urgency of AAC measures as people with bulbar-onset ALS are more susceptible to delayed evaluation and AAC intervention.



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Struggle and failure on clinical placement: a critical narrative review

Abstract

Background

Clinical placements are crucial to the development of skills and competencies in speech–language pathology (SLP) education and, more generally, a requirement of all health professional training programmes. Literature from medical education provides a context for understanding how the environment can be vital to all students’ learning. Given the increasing costs of education and demands on health services, students who struggle or fail on clinical placement place an additional burden on educators. Therefore, if more is known or understood about these students and their experience in relation to the clinical learning environment, appropriate strategies and support can be provided to reduce the burden. However, this literature does not specifically explore marginal or failing students and their experience.

Aims

To review existing research that has explored failing and struggling health professional students undertaking clinical placements and, in particular, SLP students.

Methods & Procedures

A critical narrative review was undertaken. Three electronic databases, ProQuest, CINAHL and OVID (Medline 1948–), were searched for papers exploring marginal and failing students in clinical placement contexts across all health professions, published between 1988 and 2017. Data were extracted and examined to determine the breadth of the existing research, and publications were critically appraised and major research themes identified.

Main Contribution

Sixty-nine papers were included in the review. The majority came from medicine and nursing in the United States and United Kingdom, with other allied health disciplines less well represented. The review identified key themes with the majority of papers focused on identification of at risk students and support and remediation. The review also highlighted the absence of literature relating to the student voice and in the allied health professions.

Conclusions & Implications

This review highlighted the limited research related to failing/struggling student learning in clinical contexts, and only a handful of papers have specifically addressed marginal or failing students in allied health professions. The complexity of interrelated factors in this field has been highlighted in this review. Further research needs to include the student's voice to develop greater understanding and insights of struggle and failure in clinical contexts.



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Spoken sentence production in college students with dyslexia: working memory and vocabulary effects

Abstract

Background

Individuals with dyslexia demonstrate syntactic difficulties on tasks of language comprehension, yet little is known about spoken language production in this population.

Aims

To investigate whether spoken sentence production in college students with dyslexia is less proficient than in typical readers, and to determine whether group differences can be attributable to cognitive differences between groups.

Methods & Procedures

Fifty-one college students with and without dyslexia were asked to produce sentences from stimuli comprising a verb and two nouns. Verb types varied in argument structure and morphological form and nouns varied in animacy. Outcome measures were precision (measured by fluency, grammaticality and completeness) and efficiency (measured by response times). Vocabulary and working memory tests were also administered and used as predictors of sentence production performance.

Outcomes & Results

Relative to non-dyslexic peers, students with dyslexia responded significantly slower and produced sentences that were significantly less precise in terms of fluency, grammaticality and completeness. The primary predictors of precision and efficiency were working memory, which differed between groups, and vocabulary, which did not.

Conclusions & Implications

College students with dyslexia were significantly less facile and flexible on this spoken sentence-production task than typical readers, which is consistent with previous studies of school-age children with dyslexia. Group differences in performance were traced primarily to limited working memory, and were somewhat mitigated by strong vocabulary.



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Comparison of animal, action and phonemic fluency in aphasia

Abstract

Background

The ability to generate words that follow certain constraints, or verbal fluency, is a sensitive indicator of neurocognitive impairment, and is impacted by a variety of variables.

Aims

To investigate the effect of post-stroke aphasia, elicitation category and linguistic variables on verbal fluency performance.

Methods & Procedures

Twenty-eight persons with aphasia (PWA) with a single left-hemisphere lesion and 40 age-matched neurotypical community-dwelling adults were administered three verbal fluency tasks: two semantic (animals and actions) and one phonemic (the letters F, A and S). Data analysis included comparison of total scores, clusters and perseverations. Individual responses were coded for frequency of occurrence, age of acquisition and syllable length to investigate qualitative differences in word generation.

Outcomes & Results

PWA performed worse than neurotypical participants across all verbal fluency tasks, and animal fluency scores were farthest from neurotypical performance. PWAs’ animal and action fluency were correlated with other language measures, while phonemic fluency was uncorrelated with language measures. While some PWAs showed dissociations between verbal fluency tasks, the dissociations did not pattern along with aphasia fluency. PWAs produced fewer clusters and responses with higher word frequency across all three verbal fluency tasks. Responses had earlier age of acquisition and shorter word length for animal and phonemic fluency, but not action fluency.

Conclusions & Implications

Verbal fluency, particularly animal fluency, is sensitive to even mild aphasia. PWA produced lexically simpler responses than their neurotypical peers. This study identifies the relevance of qualitative analysis of verbal fluency responses.



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Vocabulary intervention for adolescents with language disorder: a systematic review

Abstract

Background

Language disorder and associated vocabulary difficulties can persist into adolescence, and can impact on long-term life outcomes. Previous reviews have shown that a variety of intervention techniques can successfully enhance students’ vocabulary skills; however, none has investigated vocabulary intervention specifically for adolescents with language disorder.

Aims

To carry out a systematic review of the literature on vocabulary interventions for adolescents with language disorder.

Methods & Procedures

A systematic search of 14 databases and other sources yielded 1320 studies, of which 13 met inclusion criteria. Inclusion criteria were: intervention effectiveness studies with a focus on enhancing oral receptive and/or expressive vocabulary skills in the study's aims; participants in the age range 11;0–16;11 with receptive and/or expressive language difficulties of any aetiology.

Main Contribution

There was a high degree of diversity between studies. Types of intervention included: semantic intervention (four studies); comparison of phonological versus semantic intervention (two); and combined phonological–semantic intervention (seven). The strongest evidence for effectiveness was found with a combined phonological–semantic approach. The evidence suggested a potential for all models of delivery to be helpful (individual, small group and whole class).

Conclusions & Implications

Tentative evidence is emerging for the effectiveness of a phonological–semantic approach in enhancing the vocabulary skills of adolescents who have language disorder. Future research needs to refine and develop the methodologies used in this diverse group of studies in order to replicate their findings and to build consensus.



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Biosensors, Vol. 7, Pages 54: A Gal-MµS Device to Evaluate Cell Migratory Response to Combined Galvano-Chemotactic Fields

Biosensors, Vol. 7, Pages 54: A Gal-MµS Device to Evaluate Cell Migratory Response to Combined Galvano-Chemotactic Fields

Biosensors doi: 10.3390/bios7040054

Authors: Shawn Mishra Maribel Vazquez

Electric fields have been studied extensively in biomedical engineering (BME) for numerous regenerative therapies. Recent studies have begun to examine the biological effects of electric fields in combination with other environmental cues, such as tissue-engineered extracellular matrices (ECM), chemical gradient profiles, and time-dependent temperature gradients. In the nervous system, cell migration driven by electrical fields, or galvanotaxis, has been most recently studied in transcranial direct stimulation (TCDS), spinal cord repair and tumor treating fields (TTF). The cell migratory response to galvano-combinatory fields, such as magnetic fields, chemical gradients, or heat shock, has only recently been explored. In the visual system, restoration of vision via cellular replacement therapies has been limited by low numbers of motile cells post-transplantation. Here, the combinatory application of electrical fields with other stimuli to direct cells within transplantable biomaterials and/or host tissues has been understudied. In this work, we developed the Gal-MµS device, a novel microfluidics device capable of examining cell migratory behavior in response to single and combinatory stimuli of electrical and chemical fields. The formation of steady-state, chemical concentration gradients and electrical fields within the Gal-MµS were modeled computationally and verified experimentally within devices fabricated via soft lithography. Further, we utilized real-time imaging within the device to capture cell trajectories in response to electric fields and chemical gradients, individually, as well as in combinatory fields of both. Our data demonstrated that neural cells migrated longer distances and with higher velocities in response to combined galvanic and chemical stimuli than to either field individually, implicating cooperative behavior. These results reveal a biological response to galvano-chemotactic fields that is only partially understood, as well as point towards novel migration-targeted treatments to improve cell-based regenerative therapies.



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The Protein Expression Level of a Heterogeneous Gene Inserted in LIPI-1 of the Listeria ivanovii Genome Relies on Its Insertion Orientation

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Due to its capability to multiply in either phagocytic or nonphagocytic cells, and to subsequently elicit a robust cellular immune response, Listeria ivanovii (LI) is thought to be feasible for developing bacteria-based live attenuated vaccines. We previously generated several recombinant LI strains expressing Mycobacterium tuberculosis antigens. Since the expression level of heterogeneous protein was sometimes very low, we attempted to elucidate the principle of heterogeneous protein expression in such recombinant LI strains. In this study, we inserted the M. tuberculosis antigen gene Rv0129c into LI strains at the same site as the genome but with a different insertion orientation. RT-qPCR and Western blot showed that when the insertion orientation of the heterogeneous gene was opposite to the LIorfXYZ gene in the Listeria pathogenicity island 1 in the bacterial genome, the heterogeneous gene could be transcribed well but the protein expression level seemed limited, both in vitro and in vivo. When inserted at an orientation consistent with LIorfXYZ at the same site in the genome, the expected 43-kD protein was observed in vitro as well as in a mouse model. Bacterial virulence was found to have decreased after recombination. This work confirms that the protein expression level of the heterogenous gene in such genome-recombinant LI-based vaccines is related to its inserted orientation in the bacterial genome, and a foreign gene inserted at this position of LIPI-1 will abolish Listeria virulence without affecting its growth.
J Mol Microbiol Biotechnol 2017;27:269-276

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IJMS, Vol. 18, Pages 2479: Ergostane-Type Sterols from King Trumpet Mushroom (Pleurotus eryngii) and Their Inhibitory Effects on Aromatase

IJMS, Vol. 18, Pages 2479: Ergostane-Type Sterols from King Trumpet Mushroom (Pleurotus eryngii) and Their Inhibitory Effects on Aromatase

International Journal of Molecular Sciences doi: 10.3390/ijms18112479

Authors:Takashi KikuchiNaoki MotoyashikiTakeshi YamadaKanae ShibataniKiyofumi NinomiyaToshio MorikawaReiko Tanaka

Two new ergostane-type sterols; (22E)-5α,6α-epoxyergosta-8,14,22-triene-3β,7β-diol (1) and 5α,6α-epoxyergost-8(14)-ene-3β,7α-diol (2) were isolated from the fruiting bodies of king trumpet mushroom (Pleurotus eryngii), along with eight known compounds (3–10). All isolated compounds were evaluated for their inhibitory effects on aromatase. Among them, 4 and 6 exhibited comparable aromatase inhibitory activities to aminoglutethimide.



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Toxicity of 4-chloroaniline in early life-stages of zebrafish (Danio rerio): II. Cytopathology and regeneration of liver and gills after prolonged exposure to water-borne 4-chloroaniline

Ultrastructural alterations in liver and gills of embryonic and larval zebrafish (Danio rerio) following prolonged exposure to waterborne 0.05, 0.5, and 5 mg/L 4-chloroaniline for up to 31 days as well as after a 14-day regeneration period were investigated by means of light and electron microscopy. Acute toxicity was also tested at 25 and 50 mg/L. Survival of zebrafish embryos and larvae was only impaired from 25 mg/L 4-chloroaniline, but—after a transient stimulation following exposure to 0.5 mg/L—4-chloroaniline hatching was retarded after exposure to ≥5 mg/L, and fish displayed increasing rates of abnormal development and pigmentation. In contrast, hepatocytes displayed a time- and dose-dependent response from 0.05 mg/L 4-chloroaniline, including changes in nuclei, mitochondria, peroxisomes, endoplasmic reticulum, Golgi fields, lysosomes, and hepatic glycogen and lipid stores, as well as invasion of macrophages. In gills, dose-dependent effects were evident from 0.5 mg/L 4-chloroaniline and included deformation of secondary lamellae due to vacuolization and desquamation of respiratory epithelial cells in conjunction with dilation of intercellular spaces. Respiratory epithelial cells displayed progressive mitochondrial changes, induction of cytoplasmic myelinated structures, augmentation of lysosomes, and modifications of Golgi fields. Erythrocytes were severely deformed. A 14-day regeneration period was sufficient for almost complete recovery of pathological symptoms in both liver and gills. Only minor volumetric changes in hepatocellular organelles and a limited number of myelinated bodies, lysosomes, and cytoplasmic vacuoles were reminiscent of prior 4-chloroaniline exposure. In both qualitative and quantitative terms, most effects in hepatocytes after exposure of embryonic and larval zebrafish to waterborne 4-chloroaniline are comparable to the reaction of hepatocytes in adult zebrafish liver after prolonged sublethal exposure as well as in larval zebrafish after microinjection. Morphological changes in erythrocytes indicate disturbance of respiration as an additional mode of action of 4-chloroaniline.

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Genes, Vol. 8, Pages 336: Assessment of Bifidobacterium Species Using groEL Gene on the Basis of Illumina MiSeq High-Throughput Sequencing

Genes, Vol. 8, Pages 336: Assessment of Bifidobacterium Species Using groEL Gene on the Basis of Illumina MiSeq High-Throughput Sequencing

Genes doi: 10.3390/genes8110336

Authors: Lujun Hu Wenwei Lu Linlin Wang Mingluo Pan Hao Zhang Jianxin Zhao Wei Chen

The next-generation high-throughput sequencing techniques have introduced a new way to assess the gut’s microbial diversity on the basis of 16S rRNA gene-based microbiota analysis. However, the precise appraisal of the biodiversity of Bifidobacterium species within the gut remains a challenging task because of the limited resolving power of the 16S rRNA gene in different species. The groEL gene, a protein-coding gene, evolves quickly and thus is useful for differentiating bifidobacteria. Here, we designed a Bifidobacterium-specific primer pair which targets a hypervariable sequence region within the groEL gene that is suitable for precise taxonomic identification and detection of all recognized species of the genus Bifidobacterium so far. The results showed that the novel designed primer set can specifically differentiate Bifidobacterium species from non-bifidobacteria, and as low as 104 cells of Bifidobacterium species can be detected using the novel designed primer set on the basis of Illumina Miseq high-throughput sequencing. We also developed a novel protocol to assess the diversity of Bifidobacterium species in both human and rat feces through high-throughput sequencing technologies using groEL gene as a discriminative marker.



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Genes, Vol. 8, Pages 335: Differential Expression Patterns of Pleurotus ostreatus Catalase Genes during Developmental Stages and under Heat Stress

Genes, Vol. 8, Pages 335: Differential Expression Patterns of Pleurotus ostreatus Catalase Genes during Developmental Stages and under Heat Stress

Genes doi: 10.3390/genes8110335

Authors: Lining Wang Xiangli Wu Wei Gao Mengran Zhao Jinxia Zhang Chenyang Huang

Catalases are ubiquitous hydrogen peroxide-detoxifying enzymes. They participate in fungal growth and development, such as mycelial growth and cellular differentiation, and in protecting fungi from oxidative damage under stressful conditions. To investigate the potential functions of catalases in Pleurotus ostreatus, we obtained two catalase genes from a draft genome sequence of P. ostreatus, and cloned and characterized them (Po-cat1 and Po-cat2). Po-cat1 (group II) and Po-cat2 (group III) encoded putative peptides of 745 and 528 amino acids, respectively. Furthermore, the gene structures were variant between Po-cat1 and Po-cat2. Further research revealed that these two catalase genes have divergent expression patterns during different developmental stages. Po-cat1/Po-cat1 was at a barely detectable level in mycelia, accumulated gradually during reproductive growth, and was maximal in separated spores. But no catalase activity of Po-cat1 was detected by native-PAGE during any part of the developmental stages. In contrast, high Po-cat2/Po-cat2 expression and Po-cat2 activity found in mycelia were gradually lost during reproductive growth, and at a minimal level in separated spores. In addition, these two genes responded differentially under 32 °C and 40 °C heat stresses. Po-cat1 was up-regulated under both temperature conditions, while Po-cat2 was up-regulated at 32 °C but down-regulated at 40 °C. The accumulation of catalase proteins correlated with gene expression. These results indicate that the two divergent catalases in P. ostreatus may play different roles during development and under heat stress.



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