Neuroanatomical Correlates of Cognitive Dysfunction in 22q11.2 Deletion Syndrome.

22q11.2 Deletion Syndrome (22q11.2DS), the most common chromosomal microdeletion, presents as a heterogeneous phenotype characterized by an array of anatomical, behavioral, and cognitive abnormalities. Individuals with 22q11.2DS exhibit extensive cognitive deficits, both in overall intellectual capacity and focal challenges in executive functioning, attentional control, perceptual abilities, motor skills, verbal processing, as well as socioemotional operations. Heterogeneity is an intrinsic factor of the deletion's clinical manifestation in these cognitive domains. Structural imaging has identified significant changes in volume, thickness, and surface area. These alterations are closely linked and display region-specific variations with an overall increase in abnormalities following a rostral-caudal gradient. Despite the extensive literature developing around the neurocognitive and neuroanatomical profiles associated with 22q11.2DS, comparatively little research has addressed specific structure-function relationships between aberrant morphological features and deficient cognitive processes. The current review attempts to categorize these limited findings alongside comparisons to populations with phenotypic and structural similarities in order to answer to what degree structural findings can explain the characteristic neurocognitive deficits seen in individuals with 22q11.2DS. In integrating findings from structural neuroimaging and cognitive assessments, this review seeks to characterize structural changes associated with the broad neurocognitive challenges faced by individuals with 22q11.2DS.

Unruptured Arteriovenous Malformations in the Multidetector Computed Tomography Era: Frequency of Detection and Predictable Failures.

OBJECTIVES: While hemorrhage arising from ruptured arteriovenous malformations (AVMs) is usually evident on multidetector non-contrast computed tomography (NCCT), unruptured AVMs can be below the limits of detection. We performed a retrospective review of NCCT of patients with a proven diagnosis of unruptured AVM to determine if advances in CT technology have made them more apparent and what features predict their detection. MATERIAL AND METHODS: Twenty-five NCCTs met inclusion criteria of having angiography or MR proven AVM without hemorrhage, prior surgery, or other CNS disease. Demographic variables, clinical symptoms at presentation, abnormal CT imaging findings, attenuation of the superior sagittal sinus (SSS), and Spetzler-Martin grade of each AVM were recorded. We examined the relationship between AVM detection and SSS attenuation through Kruskal-Wallis test. Exploratory serial logistic principal components analysis was performed including demographics, symptoms, and CT features in the multivariate model. RESULTS: About 80% of the NCCTs showed an abnormality while 20% were normal. All those with an identifiable abnormality showed hyperdensity (80%). Logistic regression models indicate that clustered associations between several CT features, primarily calcifications, hyperdensity, and vascular prominence significantly predicted Spetzler-Martin grade (likelihood ratio 7.7, P = 0.006). SSS attenuation was significantly lower in subjects with occult AVMs when compared to those with CT abnormalities (median 47 vs. 55 HU, P < 0.04). CONCLUSION: Abnormal hyperdensity was evident in all detectable cases (80%) and multiple CT features were predictive of a higher Spetzler-Martin AVM grade. Moreover, SSS attenuation less than 50 HU was significantly correlated with a false-negative NCCT.

Radiology Performed Fluoroscopy-Guided Lumbar Punctures Decrease Volume of Diagnostic Study Interpretation - Impact on Resident Training and Potential Solutions.

OBJECTIVES: Lumbar punctures performed in radiology departments have significantly increased over the last few decades and are typically performed in academic centers by radiology trainees using fluoroscopy guidance. Performing fluoroscopy-guided lumbar punctures (FGLPs) can often constitute a large portion of a trainee's workday and the impact of performing FGLPs on the trainee's clinical productivity (i.e. dictating reports on neuroradiology cross-sectional imaging) has not been studied. The purpose of the study was to evaluate the relationship between the number of FGLPs performed and cross-sectional neuroimaging studies dictated by residents during their neuroradiology rotation (NR). MATERIAL AND METHODS: The number of FGLPs and myelograms performed and neuroimaging studies dictated by radiology residents on our neuroradiology service from July 2008 to December 2017 were retrospectively reviewed. The relationship between the number of FGLPs performed and neuroimaging studies (CT and MRI) dictated per day by residents was examined. RESULTS: Radiology residents (n = 84) performed 3437 FGLPs and myelograms and interpreted 33402 cross-sectional studies. Poisson regression demonstrated an exponential decrease in number of studies dictated daily with a rising number of FGLPs performed (P = 0.0001) and the following formula was derived: Number of expected studies dictated per day assuming no FGLPs × e-0.25 x number of FGLPs = adjusted expected studies dictated for the day. CONCLUSION: We quantified the impact performing FGLPs can have on the number of neuroimaging reports residents dictate on the NR. We described solutions to potentially decrease unnecessary FGLP referrals including establishing departmental guidelines for FGLP referrals and encouraging bedside lumbar punctures attempts before referral. We also emphasized equally distributing the FGLPs among trainees to mitigate procedural burden.

Changes in brain functional connectivity and cognition related to white matter lesion burden in hypertensive patients from SPRINT.

PURPOSE: Hypertension is a risk factor for cognitive impairment; however, the mechanisms leading to cognitive changes remain unclear. In this cross-sectional study, we evaluate the impact of white matter lesion (WML) burden on brain functional connectivity (FC) and cognition in a large cohort of hypertensive patients from the Systolic Blood Pressure Intervention Trial (SPRINT) at baseline. METHODS: Functional networks were identified from baseline resting state functional MRI scans of 660 SPRINT participants using independent component analysis. WML volumes were calculated from structural MRI. Correlation analyses were carried out between mean FC of each functional network and global WML as well as WML within atlas-defined white matter regions. For networks of interest, voxel-wise-adjusted correlation analyses between FC and regional WML volume were performed. Multiple variable linear regression models were built for cognitive test performance as a function of network FC, followed by mediation analysis. RESULTS: Mean FC of the default mode network (DMN) was negatively correlated with global WML volume, and regional WML volume within the precuneus. Voxel-wise correlation analyses revealed that regional WML was negatively correlated with FC of the DMN's left lateral temporal region. FC in this region of the DMN was positively correlated to performance on the Montreal Cognitive Assessment and demonstrated significant mediation effects. Additional networks also demonstrated global and regional WML correlations; however, they did not demonstrate an association with cognition. CONCLUSION: In hypertensive patients, greater WML volume is associated with lower FC of the DMN, which in turn is related to poorer cognitive test performance. TRIAL REGISTRATION: NCT01206062.

Unveiling the silent threat among us: leveraging health information technology in the search for asymptomatic COVID 19 healthcare workers.

Assuring the safety of both patients and healthcare workers (HCWs) in hospitals has been the primary focus of every healthcare organization during the COVID 19 pandemic. This article discusses the NIH Clinical Center's interdisciplinary approach to deploying an organizational Asymptomatic Staff Testing System.

Lower Respiratory Tract Infection with Human Metapneumovirus: Chest CT Imaging Features and Comparison with Other Viruses.

PURPOSE: Human metapneumovirus has been increasingly identified as a cause of lower respiratory tract infection in adults worldwide. The CT imaging features of human metapneumovirus in adults have not been characterized. The purpose of this paper is to determine the imaging features of human metapneumovirus and to compare them with features of other viruses. METHODS: Two clinicians retrospectively reviewed the medical records of 104 adults with lower respiratory tract infection due to human metapneumovirus at four hospitals in the northeast USA over 32 months. CT images were evaluated by two chest radiologists for airspace consolidation, bronchiectasis, bronchial wall thickening, ground-glass opacities, pleural effusion and tree-in-bud opacities and the dominant imaging pattern. Results for human metapneumovirus were compared with results previously reported for other viruses. RESULTS: Human metapneumovirus predominantly caused an airway-centric pattern (71-81/104, 68-77%) of infection characterized by bronchial wall thickening, tree-in-bud opacities, peri-bronchial consolidation and/or peri-bronchial ground-glass opacities. The airway-centric pattern has been previously reported with other paramyxoviridae (parainfluenza virus and respiratory syncytial virus). However, human metapneumovirus was significantly more likely (p = 0.03-0.001) to cause bronchopneumonia (46-55%) than parainfluenza virus (17%) or respiratory syncytial virus (21%). Follow-up CT in 41 (39%) patients with hMPV revealed resolution of findings in 38/41 (91%). CONCLUSION: The paramyxoviridae, including human metapneumovirus, are known to have a propensity to infect ciliated respiratory cells and we have demonstrated this leads to a propensity to cause bronchitis, bronchiolitis and bronchopneumonia on CT scans. Of these, human metapneumovirus is most likely to cause bronchopneumonia. Healthcare providers should consider human metapneumovirus as a cause of pneumonia on chest CT.

Epilepsy Lesion Localization is not Predicted by Developmental Venous Anomaly Location or its FDG-PET Metabolic Activity.

BACKGROUND AND PURPOSE: This study's purpose is to correlate location and metabolic activity of developmental venous anomalies (DVAs) in epilepsy patients to the seizure focus as determined by ictal/interictal encephaloelectrogram (EEG). METHODS: A retrospective search was performed for epilepsy patients with DVAs who underwent brain 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET) and magnetic resonance imaging (MRI). MRI exams were analyzed to characterize DVA location and associated structural findings. MRI and PET images were co-registered and assessment of 18 F-FDG uptake in the DVA territory was performed. The electronic medical record was reviewed for each subject to determine seizure semiology and site of seizure focus by ictal/interictal EEG. RESULTS: Twenty-eight DVAs in 25 patients were included. Twelve DVAs demonstrated regional metabolic abnormality on 18 F-FDG-PET. There was no significant correlation between DVA site and seizure focus on EEG. DVA location was concordant with EEG seizure focus in three subjects, and all three demonstrated hypometabolism on 18 F-FDG-PET. This significance remains indeterminate, as one of these DVAs was associated with cavernoma, which could serve as the true seizure focus, and one of the patients underwent resection of the DVA without decrease in seizure frequency. Furthermore, there was no statistically significant relationship between DVA metabolic activity and DVA-EEG lobar or laterality concordance. CONCLUSIONS: In this sample, there is no significant correlation between location of DVA and seizure focus, and hypometabolism within the DVA territory is not predictive of EEG/DVA co-localization. As use of 18 F-FDG-PET for evaluation of epilepsy increases, knowledge of this poor correlation is important to avoid diagnostic confusion and potentially unnecessary surgery in epilepsy patients.

Genetic influences on neonatal cortical thickness and surface area.

Genetic and environmental influences on cortical thickness (CT) and surface area (SA) are thought to vary in a complex and dynamic way across the lifespan. It has been established that CT and SA are genetically distinct in older children, adolescents, and adults, and that heritability varies across cortical regions. Very little, however, is known about how genetic and environmental factors influence infant CT and SA. Using structural MRI, we performed the first assessment of genetic and environmental influences on normal variation of SA and CT in 360 twin neonates. We observed strong and significant additive genetic influences on total SA (a2 = 0.78) and small and nonsignificant genetic influences on average CT (a2 = 0.29). Moreover, we found significant genetic overlap (genetic correlation = 0.65) between these global cortical measures. Regionally, there were minimal genetic influences across the cortex for both CT and SA measures and no distinct patterns of genetic regionalization. Overall, outcomes from this study suggest a dynamic relationship between CT and SA during the neonatal period and provide novel insights into how genetic influences shape cortical structure during early development.

Reduced Intercarotid Artery Distance in Syndromic and Isolated Brachycephaly.

INTRODUCTION: The morphology of the skull base can be altered in craniosynostoses. The objective of this study is to evaluate the reduced intercarotid artery distance in the lacerum segment in patients with syndromic and isolated brachycephaly. MATERIALS AND METHODS: The distances between the inner walls of the carotid canal at the lacerum segment were measured on high-resolution CT scans in children with Crouzon (25), Pfeiffer (21), Apert (26), Saethre-Chotzen (7) syndromes, isolated bicoronal synostosis (9), and compared to an age-matched control group (30). RESULTS: A significantly smaller mean distance between carotid canal walls was observed in Crouzon (11.1 ± 4.9 mm), Pfeiffer (9.6 ± 5.1 mm), Apert (12.3 ± 4.3 mm), Saethre-Chotzen (14.8 ± 3.0 mm) syndromes, and isolated bicoronal synostosis (14.9 ± 3.7 mm) as compared to the control group (19.7 ± 2.4 mm, P < 0.001, P < 0.001, P < 0.001, P = 0.005, and P = 0.002, respectively). There was no statistically significant difference in intercarotid canal distance among the Apert, Saethre-Chotzen and isolated bicoronal synostosis groups. Overall, the brachycephalic group showed reduced intercarotid canal distance comparing to controls (P < 0.001). DISCUSSION AND CONCLUSIONS: There is significant reduction of the distance between carotid canals in brachycephalic patients. This distance is more significantly altered in FGFR-related brachycephaly syndromes (especially Crouzon and Pfeiffer syndromes), than Saethre-Chotzen syndrome (TWIST1 mutation) and isolated non-syndromic bicoronal synostosis. This study highlights the importance of FGFRs in shaping the skull base. Altered vascular course of the internal carotid arteries can have important implications in planning skull base surgery in brachycephalic patients.

Trends in Fluoroscopy Time in Fluoroscopy-Guided Lumbar Punctures Performed by Trainees Over an Academic Year.

RATIONALE AND OBJECTIVES: Fluoroscopy-guided lumbar puncture (FGLP) is an operator-dependent procedure that can contribute to lifetime cumulative radiation dose. Benchmark fluoroscopic times (FTs) have been published for ranges of body mass index (BMI), but trends in FT in FGLPs performed by neuroradiology trainees during their training have not been studied. The purpose of this study was to investigate the trends in FTs in FGLPs performed by neuroradiology fellows in an academic year. MATERIALS AND METHODS: We retrospectively reviewed FGLPs performed at our institution from July 2013 to June 2015 and determined the FT average and standard deviation of residents and non-neuroradiology fellows, neuroradiology fellows, and neuroradiology attendings. We used the Kruskal-Wallis test to evaluate group differences in FT in operator groups and academic quarters and by patient age, BMI, and needle length. Linear and Poisson regression analyses were performed to directly examine the relationship between the number of FGLPs performed and FTs. RESULTS: A total of 776 patients had successful FGLPs; 594 cases (77%) were performed by neuroradiology fellows (n = 14). The average FT and variance for neuroradiology fellows significantly decreased over the year (P = 0.004 and P < 0.001) with an estimated decrease of 0.01 minute of FT per FGLP. BMI, long needle length, and age ≥65 years old significantly affected the average FT (P = 0.03, P < 0.001, and P < 0.001) and FT decreased in all of these subgroups in the academic year. CONCLUSIONS: FT in FGLP cases performed by neuroradiology fellows decreases during the year. Our data can be utilized by radiology training programs and practices as a benchmark to monitor individual operator FT.

Utility of fat-suppressed sequences in differentiation of aggressive vs typical asymptomatic haemangioma of the spine.

OBJECTIVE: While haemangiomas are common benign vascular lesions involving the spine, some behave in an aggressive fashion. We investigated the utility of fat-suppressed sequences to differentiate between benign and aggressive vertebral haemangiomas. METHODS: Patients with the diagnosis of aggressive vertebral haemangioma and available short tau inversion-recovery or T2 fat saturation sequence were included in the study. 11 patients with typical asymptomatic vertebral body haemangiomas were selected as the control group. Region of interest signal intensity (SI) analysis of the entire haemangioma as well as the portion of each haemangioma with highest signal on fat-saturation sequences was performed and normalized to a reference normal vertebral body. RESULTS: A total of 8 patients with aggressive vertebral haemangioma and 11 patients with asymptomatic typical vertebral haemangioma were included. There was a significant difference between total normalized mean SI ratio (3.14 vs 1.48, p = 0.0002), total normalized maximum SI ratio (5.72 vs 2.55, p = 0.0003), brightest normalized mean SI ratio (4.28 vs 1.72, p < 0.0001) and brightest normalized maximum SI ratio (5.25 vs 2.45, p = 0.0003). Multiple measures were able to discriminate between groups with high sensitivity (>88%) and specificity (>82%). CONCLUSION: In addition to the conventional imaging features such as vertebral expansion and presence of extravertebral component, quantitative evaluation of fat-suppression sequences is also another imaging feature that can differentiate aggressive haemangioma and typical asymptomatic haemangioma. ADVANCES IN KNOWLEDGE: The use of quantitative fat-suppressed MRI in vertebral haemangiomas is demonstrated. Quantitative fat-suppressed MRI can have a role in confirming the diagnosis of aggressive haemangiomas. In addition, this application can be further investigated in future studies to predict aggressiveness of vertebral haemangiomas in early stages.

Back to the future: sagittal CT in the evaluation of COPD.

OBJECTIVES: To identify features of obstructive airway disease on sagittal reconstruction, compare the accuracy of findings to traditional imaging characteristics of COPD, and determine the fraction of additional cases identified using new characteristics. METHODS: The study was approved by the centre's Institutional Review Board and is HIPAA compliant. Two hundred sixteen patients with HRCT and spirometry within a 3-month window were included. Four radiologists evaluated each HRCT for traditional characteristics of COPD and new quantitative and qualitative features of obstruction on axial and sagittal reconstructions. Imaging characteristics were assessed for correlation with the spirometric diagnosis of obstructive airway disease. RESULTS: Quantitative and qualitative findings on sagittal reconstruction are highly specific for COPD (specificity >90 %). Features of hyperinflation on sagittal reconstruction are more accurate predictors of obstruction than traditional axial measures, with greater interobserver reliability (hyperinflation left hemidiaphragm: accuracy: 70.08 % ± 2.49 %; kappa: 0.511 versus traditional measures: accuracy: 62.00 % ± 5.38 %; kappa: 0.407). Sagittal reconstruction identified 27-70 % more patients with COPD than traditional axial findings (p < 0.05). CONCLUSIONS: Analysis of sagittal reconstruction enables greater accuracy and specificity in the diagnosis of obstructive airway disease compared to traditional measures on axial imaging. Use of sagittal reconstructions can help identify up to 70 % more patients with COPD than traditional imaging findings alone. KEY POINTS: • HRCT sagittal reconstruction is useful in the evaluation of obstructive lung disease. • Findings on sagittal reconstructions allow physicians to more accurately diagnose COPD. • Routine use of sagittal reconstructions increases the sensitivity for diagnosing COPD.

Small pulmonary artery defects are not reliable indicators of pulmonary embolism.

OBJECTIVES: To evaluate the rate of agreement of pulmonary embolism diagnosis in computed tomography (CT) pulmonary angiogram studies and to evaluate the rate of inaccurate interpretations in the community hospital setting. METHODS: Using the keywords "pulmonary embolism/embolus/emboli," the radiology information system was searched for CT pulmonary angiograms performed over a 3-year period at three U.S. community hospitals. Studies containing probable or definite pulmonary emboli were independently reviewed by four subspecialty thoracic radiologists. MEASUREMENTS AND MAIN RESULTS: Agreement about the presence of pulmonary embolism progressively decreased with decreasing diameter of pulmonary vascular lesions (P < 0.0001). There was a sharp fall in observer agreement for pulmonary embolism of subsegmental lesions (P < 0.0001). The frequency of agreement decreased with decreasing quality of the imaging examination (P < 0.0001). Community radiologists were prone to false-positive pulmonary embolism diagnosis of subsegmental and/or small pulmonary arterial defects. The probability of a false-positive diagnosis and indeterminate examinations progressively increased with: (1) more peripheral location of the lesion, (2) decreased size (short-axis diameter) of the lesion, and (3) diminishing quality of the CT examination. Forty-eight of 177 (27%) of subsegmental vascular defects identified by community radiologists were deemed indeterminate, and 27 of 177 (15%) of subsegmental vascular defects were judged to be false positive for pulmonary embolism by the consensus diagnosis. Fifty-four of 274 (20%) vascular defects with short axis less than 6 mm were indeterminate for pulmonary embolism, and 37 of 274 (14%) of vascular defects with short axis less than 6 mm were false positive for pulmonary embolism. Eleven of 13 (85%) of vascular lesions identified as pulmonary emboli on the lowest-quality CT examinations were false positive or indeterminate for pulmonary embolism. False-positive examinations were most often due to respiratory motion artifact (19/38, 50%). CONCLUSIONS: There is relatively poor interobserver agreement for subsegmental and/or small pulmonary artery defects, especially in CT pulmonary angiograms degraded by technical artifacts. These factors can lead to an increased frequency of inaccurate interpretation or indeterminate diagnosis of subsegmental and/or small defects. Caution is indicated in interpreting the significance of small vascular defects in CT pulmonary angiograms.

Match day: online search trends reflect growing interest in IR training.

Google Trends was used to characterize the relationship between the interventional radiology (IR) applicant pool and related Internet queries for "IR fellowship" from July 2006 to July 2013. Results were compared with National Residency Match Panel data by regression analysis and one-way analysis of variance. Search traffic for IR fellowship demonstrated a statistically significant linear annual increase (R(2) = 0.87; P = .0013). Total IR applicants increased by 184% (R(2) = 0.98; P = .0216). Search traffic was predictive of applicants for each match year (R(2) = 0.92; P = .0004) and programs filled (R(2) = 0.93; P = .0003). Internet queries mirror trainee professional interests, with significant increases in search traffic related to IR fellowship and strong correlation with growth in applicants.

A seroprevalence study of primate workers for asymptomatic rhesus cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus (HCMV) infection can cause severe disease in neonates and immunocompromised persons, and infectious mononucleosis in healthy adults. While, rhesus CMV (RhCMV) infects human cells in culture, it is unknown whether the virus can infect humans. OBJECTIVES: We sought to determine whether primate workers, including those with injuries from animals, might be infected asymptomatically with RhCMV. STUDY DESIGN: We developed serologic assays that distinguish RhCMV from HCMV antibodies. We tested two groups of primate workers: those with documented injuries or mucosal splashes associated with rhesus macaques, and those with no documented exposure who worked with these animals. RESULTS: None of over 200 primate workers, including 119 with injuries or mucosal splashes associated with exposures to macaques, were seropositive for RhCMV. CONCLUSIONS: The frequency of asymptomatic RhCMV infection in persons who work with rhesus macaques was <0.5% (<1/200 primate workers).

Comparative taphonomy, taphofacies, and bonebeds of the Mio-Pliocene Purisima Formation, central California: strong physical control on marine vertebrate preservation in shallow marine settings.

BACKGROUND: Taphonomic study of marine vertebrate remains has traditionally focused on single skeletons, lagerstätten, or bonebed genesis with few attempts to document environmental gradients in preservation. As such, establishment of a concrete taphonomic model for shallow marine vertebrate assemblages is lacking. The Neogene Purisima Formation of Northern California, a richly fossiliferous unit recording nearshore to offshore depositional settings, offers a unique opportunity to examine preservational trends across these settings. METHODOLOGY/PRINCIPAL FINDINGS: Lithofacies analysis was conducted to place vertebrate fossils within a hydrodynamic and depositional environmental context. Taphonomic data including abrasion, fragmentation, phosphatization, articulation, polish, and biogenic bone modification were recorded for over 1000 vertebrate fossils of sharks, bony fish, birds, pinnipeds, odontocetes, mysticetes, sirenians, and land mammals. These data were used to compare both preservation of multiple taxa within a single lithofacies and preservation of individual taxa across lithofacies to document environmental gradients in preservation. Differential preservation between taxa indicates strong preservational bias within the Purisima Formation. Varying levels of abrasion, fragmentation, phosphatization, and articulation are strongly correlative with physical processes of sediment transport and sedimentation rate. Preservational characteristics were used to delineate four taphofacies corresponding to inner, middle, and outer shelf settings, and bonebeds. Application of sequence stratigraphic methods shows that bonebeds mark major stratigraphic discontinuities, while packages of rock between discontinuities consistently exhibit onshore-offshore changes in taphofacies. CONCLUSIONS/SIGNIFICANCE: Changes in vertebrate preservation and bonebed character between lithofacies closely correspond to onshore-offshore changes in depositional setting, indicating that the dominant control of preservation is exerted by physical processes. The strong physical control on marine vertebrate preservation and preservational bias within the Purisima Formation has implications for paleoecologic and paleobiologic studies of marine vertebrates. Evidence of preservational bias among marine vertebrates suggests that careful consideration of taphonomic overprint must be undertaken before meaningful paleoecologic interpretations of shallow marine vertebrates is attempted.

Effect of facial material softness and applied force on face mask dead volume, face mask seal, and inhaled corticosteroid delivery through an idealized infant replica.

BACKGROUND: During the aerosol delivery device design and optimization process, in vitro lung dose (LD) measurements are often performed using soft face models, which may provide a more clinically relevant representation of face mask dead volume (MDV) and face mask seal (FMS) than hard face models. However, a comparison of MDV, FMS, and LD for hard and soft face models is lacking. METHODS: Metal, silicone, and polyurethane represented hard, soft, and very soft facial materials, respectively. MDV was measured using a water displacement technique. FMS was measured using a valved holding chamber (VHC) flow rate technique. The LD of beclomethasone dipropionate (BDP) delivered via a 100-µg Qvar® pressurized metered dose inhaler with AeroChamber Plus® Flow-Vu® VHC and Small Mask, defined as that which passes through the nasal airways of the idealized infant geometry, was measured using a bias tidal flow system with a filter. MDV, FMS, and LD were measured at 1.5 lb and 3.5 lb of applied force. A mathematical model was used to predict LD based on experimental measurements of MDV and FMS. RESULTS: Experimental BDP LD measurements for ABS, silicone, and polyurethane at 1.5 lb were 0.9 (0.6) µg, 2.4 (1.9) µg, and 19.3 (0.9) µg, respectively. At 3.5 lb, the respective LD was 10.0 (1.5) µg, 13.8 (1.4) µg, and 14.2 (0.9) µg. Parametric analysis with the mathematical model showed that differences in FMS between face models had a greater impact on LD than differences in MDV. CONCLUSIONS: The use of soft face models resulted in higher LD than hard face models, with a greater difference at 1.5 lb than at 3.5 lb. A lack of a FMS led to decreased dose consistency; therefore, a sealant should be used when measuring LD with a hard ABS or soft silicone face model at 1.5 lb of applied force or less.

Occupational exposure to hepatitis C virus: early T-cell responses in the absence of seroconversion in a longitudinal cohort study.

BACKGROUND: T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss. METHODS: Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months. RESULTS: All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell response and 42% developed responses in interferon-gamma enzyme-linked immunosorbent spot assays, with 29 healthy HCV-unexposed controls used to define assay cutoffs. The response prevalence was associated with the transmission risk score. T-cell responses peaked at week 4 and returned to baseline by week 12 after exposure. They predominantly targeted nonstructural HCV proteins, which are not part of the HCV particle and thus must have been synthesized in infected cells. CONCLUSIONS: Subclinical transmission of HCV occurs frequently, resulting in infection and synthesis of nonstructural proteins despite undetectable systemic viremia. T-cell responses are more sensitive indicators of this low-level HCV exposure than antibodies.