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Background Exposure to inhalational hazards during post-9/11 deployment to Southwest Asia and Afghanistan puts military personnel at risk for respiratory symptoms and disease. Pulmonary function and qualitative chest high resolution computed tomography (HRCT) are often normal in “deployers” with persistent respiratory symptoms. We explored the utility of quantitative HRCT imaging markers of large and small airways abnormalities, including airway wall thickness, emphysema, and air trapping, in symptomatic deployers with clinically-confirmed lung disease compared to controls. Methods Chest HRCT images from 45 healthy controls and 82 symptomatic deployers with asthma, distal lung disease or both were analyzed using Thirona Lung quantification software to calculate airway wall thickness (by Pi10), emphysema (by percentage of lung volume with attenuation < -950 Hounsfield units [LAA%-950]), and three parameters of air trapping (expiratory/inspiratory total lung volume and mean lung density ratios, and LAA%-856). SAS v.9.4 was used to compare demographic and clinical characteristics between deployers and controls using Chi-Square, Fisher Exact or t-tests. Linear regression was used to assess relationships between pulmonary function and quantitative imaging findings. Results Gender and smoking status were not statistically significantly different between groups, but deployers were significantly younger than controls (42 vs 58 years, p < 0.0001), had higher body mass index (31 vs 28 kg/m 2 , p = 0.01), and had fewer total smoking pack-years (8 vs. 26, p = 0.007). Spirometric measures were not statistically significantly different between groups. Pi10 and LAA%-950 were significantly elevated in deployers compared to controls in unadjusted analyses, with the emphysema measure remaining significantly higher in deployers after adjustment for age, sex, smoking, BMI, and expiratory total lung volume. Air trapping parameters were more common in control images, likely due to differences in age and smoking between groups. Among deployers, LAA%-950 and Pi10 were significantly correlated with spirometric markers of obstruction based on ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) and/or percent predicted FEV1. Conclusions Quantitative chest HRCT imaging analysis identifies emphysema in deployers with asthma and distal lung disease, and may be useful in detecting and monitoring deployment-related lung disease in a population where spirometry is typically normal.

CT is crucial for diagnosing chest diseases, with image quality affected by spatial resolution. Thick-slice CT remains prevalent in practice due to cost considerations, yet its coarse spatial resolution may hinder accurate diagnoses. Our multicenter study develops a deep learning synthetic model with Convolutional-Transformer hybrid encoder-decoder architecture for generating thin-slice CT from thick-slice CT on a single center (1576 participants) and access the synthetic CT on three cross-regional centers (1228 participants). The qualitative image quality of synthetic and real thin-slice CT is comparable ( p  = 0.16). Four radiologists’ accuracy in diagnosing community-acquired pneumonia using synthetic thin-slice CT surpasses thick-slice CT ( p  < 0.05), and matches real thin-slice CT ( p  > 0.99). For lung nodule detection, sensitivity with thin-slice CT outperforms thick-slice CT ( p  < 0.001) and comparable to real thin-slice CT ( p  > 0.05). These findings indicate the potential of our model to generate high-quality synthetic thin-slice CT as a practical alternative when real thin-slice CT is preferred but unavailable.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease characterized by worsening dyspnea and lung function and has a median survival of 2–3 years. Forced vital capacity (FVC) is the primary endpoint used most commonly in IPF clinical trials as it is the best surrogate for mortality. This study assessed quantitative scores from high-resolution computed tomography (HRCT) developed by machine learning as a secondary efficacy endpoint in a 26-week phase II study of BMS-986020 – an LPA1 receptor antagonist – in patients with IPF. Methods: HRCT scans from 96% (137/142) of randomized subjects were utilized. Quantitative lung fibrosis (QLF) scores were calculated from the HRCT images. QLF improvement was defined as ⩾2% reduction in QLF score from baseline to week 26. Results: In the placebo arm, 5% of patients demonstrated an improvement in QLF score at week 26 compared with 15% and 27% of patients in the BMS-986020 600 mg once daily (QD) and twice daily (BID) arms, respectively [versus placebo: p = 0.08 (600 mg QD); p = 0.0098 (600 mg BID)]. Significant correlations were found between changes in QLF and changes in percent predicted FVC, diffusing capacity for carbon monoxide (DLCO), and shortness of breath at week 26 (ρ = −0.41, ρ = −0.22, and ρ = 0.27, respectively; all p < 0.01). Conclusions: This study demonstrated the utility of quantitative HRCT as an efficacy endpoint for IPF in a double-blind, placebo-controlled clinical trial setting. The reviews of this paper are available via the supplemental material section.

Patient satisfaction has become an essential metric in addition to the type of care they receive. Phone calls, emails, and text to patients after their healthcare visit are the typical way of obtaining the data reflecting patient satisfaction. The purpose of this retrospective quality improvement study is to compare the traditional post-outpatient clinic survey method with an onsite concise two-question survey using a tablet method immediately after the patient visit using Net Promoter Score (NPS) questions. Data were collected retrospectively from February to August 2018 from an outpatient subspecialty clinic in southern California using an existing database from two different sources: the traditional method (TM) and the tablet-based tool (TBT), using NPS. The TM data were obtained from a third-party company using two questions via phone, email, and text collected 2-4 weeks after the patient's visit. The TBT has only two questions that were given to patients upon their visit check-out. These two questions assessed both provider and clinic's performance using the NPS method. In total, there were 1708 patients seen from February to August 2018. In the TM, the total outgoing messages during this period were 580 (34.0%) with 156 responses (27%). In the TBT, 648 out of 1708 (37.9%) surveys were collected with a 100% response rate. The NPS score showed that 99.2% of the providers were promoters. The NPS score for the clinic was 96% which reflects a promoter score. Our results indicate that when using the TBT immediately after their visit to the clinic, a higher response rate was noted. In addition, both methods had similar outcomes in terms of patient satisfaction NPS scores. Future prospective studies with a larger sample size are warranted to evaluate the effectiveness of the TBT tool in assessing patient satisfaction.

BackgroundPrior work suggests different interstitial lung diseases (ILDs) that share the radiological usual interstitial pneumonia (UIP) pattern have an overall worse prognosis. However, epidemiological data with longitudinal sampling and replication remains lacking.MethodsData was used from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=932) and a meta-cohort of ILD research studies (n=1579). Linear mixed-effects models and Cox proportional hazard models were used to determine forced vital capacity (FVC) slopes and 5-year transplant-free survival, respectively, by ILD diagnosis and UIP radiological pattern. Secondarily, we examined FVC and survival by diagnosis and radiological fibrosis quantified by data-driven texture analysis (DTA) in the PFF-PR. Models were adjusted for age, sex, smoking and antifibrotic and immunosuppression medication use.ResultsThe proportions of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease (CTD)-ILD were the following for PFF-PR (70%, 11%, 19%) and meta-cohort (21%, 32%, 47%). In the PFF-PR, CTD-ILD with UIP CT pattern was associated with slower FVC decline (−34.4 mL/year) compared with IPF (−158.4 mL/year) and longer transplant-free survival (HR 0.50, 95% CI 0.29 to 0.85). This was replicated in the meta cohort for FVC (−53.1 vs −185.9 mL/year, p<0.0001) and survival (HR 0.38, 95% CI 0.27 to 0.53). A similar pattern was seen using DTA to objectively categorise patients into higher and lower radiological fibrosis. Between IPF and FHP-UIP, FVC decline was not significantly different in the PFF-PR (−203.4 vs −158.4 mL/year, p=0.58) and meta-cohort (−124.0 vs −185.9 mL/year, p=0.25).ConclusionsEven in the presence of a UIP CT pattern, there may still be differences in lung function over time and survival, particularly for CTD-ILD.

Electrons with a linear energy/momentum dispersion are called massless Dirac electrons and represent the low-energy excitations in exotic materials such as graphene and topological insulators. Dirac electrons are characterized by notable properties such as a high mobility, a tunable density and, in topological insulators, a protection against backscattering through the spin–momentum locking mechanism. All those properties make graphene and topological insulators appealing for plasmonics applications. However, Dirac electrons are expected to present also a strong nonlinear optical behaviour. This should mirror in phenomena such as electromagnetic-induced transparency and harmonic generation. Here we demonstrate that in Bi 2 Se 3 topological insulator, an electromagnetic-induced transparency is achieved under the application of a strong terahertz electric field. This effect, concomitantly determined by harmonic generation and charge-mobility reduction, is exclusively related to the presence of Dirac electron at the surface of Bi 2 Se 3 , and opens the road towards tunable terahertz nonlinear optical devices based on topological insulator materials. The terahertz response of topological insulator surface states, in which relativistic electrons are protected from backscattering, possesses potential optic and plasmonic applications. Here, the authors demonstrate a nonlinear absorption response of Bi 2 Se 3 to terahertz electric fields.

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole 1 – 4 . The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity 5 . With a baseline of 17 years of observations, there was a shift in the jet’s transverse position, possibly arising from an 8- to 10-year quasi-periodicity 3 . However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense–Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation. This study analyses radio observations of the jet in galaxy M87, from which the existence of a spinning black hole that induces Lense–Thirring precession of a misaligned accretion disk is inferred.

Human mesenchymal stem/progenitor cells (hMSCs) from bone marrow and other tissues are currently being administered to large numbers of patients even though there are no biomarkers that accurately predict their efficacy in vivo. Using a mouse model of chemical injury of the cornea, we found that bone-marrow–derived hMSCs isolated from different donors varied widely in their efficacy in modulating sterile inflammation. Importantly, RT-PCR assays of hMSCs for the inflammation-modulating protein TSG-6 expressed by the TNFα-stimulated gene 6 ( TSG-6 or TNFAIP6 ) predicted their efficacy in sterile inflammation models for corneal injury, sterile peritonitis, and bleomycin-induced lung injury. In contrast, the levels of TSG-6 mRNA were negatively correlated with their potential for osteogenic differentiation in vitro and poorly correlated with other criteria for evaluating hMSCs. Also, a survey of a small cohort suggested that hMSCs from female donors compared with male donors more effectively suppressed sterile inflammation, expressed higher levels of TSG-6 , and had slightly less osteogenic potential. Significance The clinical trials with human mesenchymal stem/progenitor cells (hMSCs) from bone marrow and other tissues are proceeding even though cultures of the cells are heterogeneous and there is large variability among preparations of hMSCs due to differences among donors, culture conditions, and inconsistent tissue sampling. However, there is currently no in vitro bioassay for the evaluation of hMSC efficacy in vivo. Therefore, the value of the data obtained from current clinical trials may well be compromised by variations in the quality of the hMSCs used. This study provides, to our knowledge, the first biomarker that can predict the efficacy of hMSCs in suppressing sterile inflammation in vivo.

Necrotizing enterocolitis (NEC) is an idiopathic, inflammatory bowel necrosis of premature infants. Clinical studies have linked NEC with antecedent red blood cell (RBC) transfusions, but the underlying mechanisms are unclear. Here we report a neonatal murine model to investigate this association. C57BL/6 mouse pups rendered anemic by timed phlebotomy and then given RBC transfusions develop NEC-like intestinal injury with prominent necrosis, inflammation, and submucosal edema/separation of the lamina propria in the ileocecal region and colon within 12–24 h. The anemic intestine is infiltrated by inflammatory macrophages, which are activated in situ by RBC transfusions via a Toll-like receptor (TLR)-4-mediated mechanism and cause bowel injury. Chelation of RBC degradation products with haptoglobin, absence of TLR4, macrophage depletion, and inhibition of macrophage activation is protective. Intestinal injury worsens with increasing severity and the duration of anemia prior to transfusion, indicating a need for the re-evaluation of current transfusion guidelines for premature infants. The development of neonatal necrotising enterocolitis has been temporally associated with red blood cell transfusions in retrospective human studies. Here, the authors develop a neonatal mouse model of necrotising enterocolitis in anaemic mice receiving red blood cell transfusion that recapitulates features of the human condition.

Background. We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. Methods. Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. Results. Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%–12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%–52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. Conclusions. This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.