Association of Internal Medicine Point of Care Ultrasound (POCUS) with Length of Stay, Hospitalization Costs, and Formal Imaging: a Prospective Cohort Study.

Background: Point of care ultrasound (POCUS) use has rapidly expanded among internal medicine (IM) physicians in practice and residency training programs. Many benefits have been established; however, studies demonstrating the impact of POCUS on system metrics are few and mostly limited to the emergency department or intensive care setting. The study objective was to evaluate the impact of inpatient POCUS on patient outcomes and hospitalization metrics. Methods: Prospective cohort study of 12,399 consecutive adult admissions to 22 IM teaching attendings, at a quaternary care teaching hospital (7/1/2011-6/30/2015), with or without POCUS available during a given hospitalization. Multivariable regression and propensity score matching (PSM) analyses compared multiple hospital metric outcomes (costs, length of stay, radiology-based imaging, satisfaction, etc.) between the "POCUS available" vs. "POCUS unavailable" groups as well as the "POCUS available" subgroups of "POCUS used" vs. "POCUS not used". Results: Patients in the "POCUS available" vs. "POCUS unavailable" group had lower mean total and per-day hospital costs ($17,474 vs. $21,803, p<0.001; $2,805.88 vs. $3,557.53, p<0.001), lower total and per-day radiology cost ($705.41 vs. $829.12, p<0.001; $163.11 vs. $198.53, p<0.001), fewer total chest X-rays (1.31 vs. 1.55, p=0.01), but more chest CTs (0.22 vs 0.15; p=0.001). Mean length of stay (LOS) was 5.77 days (95% CI = 5.63, 5.91) in the "POCUS available" group vs. 6.08 95% CI (5.66, 6.51) in the "POCUS unavailable" group (p=0.14). Within the "POCUS available" group, cost analysis with a 4:1 PSM (including LOS as a covariate) compared patients receiving POCUS vs. those that could have but did not, and also showed total and per-day cost savings in the "POCUS used" subgroup ($15,082 vs. 15,746; p<0.001 and $2,685 vs. $2,753; p=0.04). Conclusions: Availability and selected use of POCUS was associated with a meaningful reduction in total hospitalization cost, radiology cost, and chest X-rays for hospitalized patients.

RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing.

RNA splicing is an important biological process associated with cancer initiation and progression. However, the contribution of alternative splicing to pancreatic cancer (PDAC) development is not well understood. Here, we identify an enrichment of RNA binding proteins (RBPs) involved in splicing regulation linked to PDAC progression from a forward genetic screen using Sleeping Beauty insertional mutagenesis in a mouse model of pancreatic cancer. We demonstrate downregulation of RBFOX2, an RBP of the FOX family, promotes pancreatic cancer progression and liver metastasis. Specifically, we show RBFOX2 regulates exon splicing events in transcripts encoding proteins involved in cytoskeletal remodeling programs. These exons are differentially spliced in PDAC patients, with enhanced exon skipping in the classical subtype for several RBFOX2 targets. RBFOX2 mediated splicing of ABI1, encoding the Abelson-interactor 1 adapter protein, controls the abundance and localization of ABI1 protein isoforms in pancreatic cancer cells and promotes the relocalization of ABI1 from the cytoplasm to the periphery of migrating cells. Using splice-switching antisense oligonucleotides (AONs) we demonstrate the ABI1 ∆Ex9 isoform enhances cell migration. Together, our data identify a role for RBFOX2 in promoting PDAC progression through alternative splicing regulation.

Kurtosis analysis of sounds from down-the-hole pile installation and the implications for marine mammal auditory impairment.

Sounds from down-the-hole pile installation contain both impulsive and non-impulsive components. Kurtosis values (ß) were determined for two datasets to investigate the impulsiveness of piling sounds. When the hammer struck the pile(s), ß was 21-30 at 10 m and approximately 10 at 200 m. When the hammer was used for drilling without contacting the pile, ß was 4-6 at all distances. These findings suggest that a simple dichotomy of classifying sounds as impulsive or non-impulsive may be overly simplistic for assessing marine mammal auditory impacts and studies investigating the impacts from complex sound fields are needed.

Discovery and Mechanism of Small Molecule Inhibitors Selective for the Chromatin-Binding Domains of Oncogenic UHRF1.

Chromatin abnormalities are common hallmarks of cancer cells, which exhibit alterations in DNA methylation profiles that can silence tumor suppressor genes. These epigenetic patterns are partly established and maintained by UHRF1 (ubiquitin-like PHD and RING finger domain-containing protein 1), which senses existing methylation states through multiple reader domains, and reinforces the modifications through recruitment of DNA methyltransferases. Small molecule inhibitors of UHRF1 would be important tools to illuminate molecular functions, yet no compounds capable of blocking UHRF1-histone binding in the context of the full-length protein exist. Here, we report the discovery and mechanism of action of compounds that selectively inhibit the UHRF1-histone interaction with low micromolar potency. Biochemical analyses reveal that these molecules are the first inhibitors to target the PHD finger of UHRF1, specifically disrupting histone H3 arginine 2 interactions with the PHD finger. Importantly, this unique inhibition mechanism is sufficient to displace binding of full-length UHRF1 with histones in vitro and in cells. Together, our study provides insight into the critical role of the PHD finger in driving histone interactions, and demonstrates that targeting this domain through a specific binding pocket is a tractable strategy for UHRF1-histone inhibition.

Acoustic characteristics from an in-water down-the-hole pile drilling activity.

Sound generated by pile installation using a down-the-hole (DTH) hammer is not well documented and differs in character from sound generated by conventional impact and vibratory pile driving. This paper describes underwater acoustic characteristics from DTH pile drilling during the installation of 0.84-m shafts within 1.22-m steel piles in Ketchikan, Alaska. The median single-strike sound exposure levels were 138 and 142 dB re 1 µPa2s at 10 m for each of the two piles, with cumulative sound exposure levels of 185 and 193 dB re 1 µPa2s at 10 m, respectively. The sound levels measured at Ketchikan were significantly lower than previous studies, and the sound was determined to be non-impulsive in this study as compared to impulsive in previous studies. These differences likely result from the DTH hammer not making direct contact with the pile, as had been the case in previous studies. Therefore, we suggest using the term DTH pile drilling to distinguish from DTH pile driving when the hammer strikes the pile. Further research is needed to investigate DTH piling techniques and associated sound-generating mechanisms and to differentiate the various types of sound emitted, which has important implications for the underwater sound regulatory community.

Underwater noise characterization of down-the-hole pile driving activities off Biorka Island, Alaska.

Although down-the-hole (DTH) pile driving is increasingly used for in-water pile installation, the characteristics of underwater noise from DTH pile driving is largely undocumented and unstudied. This study presents a comprehensive analysis of the noise characteristics during DTH pile driving of two steel pipe piles in shallow waters off southeast Alaska. The results showed that single-strike sound exposure levels measured at 10 m were 147 and 145 dB re 1 µPa2s with a total of 21,742 and 38,631 hammer strikes, with cumulative sound exposure levels to install each pile at 192 and 191 dB re 1 µPa2s, respectively. Though noise levels from a single strike was lower than impact pile driving of a similar pile, the cumulative sound exposure levels are likely comparable due to the much higher striking rate.

Developing an AI project.

Artificial intelligence applications can very powerful in areas of speech recognition, image processing and identification, medical diagnosis and clustering to name a few. There is a perception that developing your own artificial intelligence (AI) application can be a daunting task, requiring in-depth knowledge and programming skills. This is not entirely true since many desktop and laptop systems have computing power that can accommodate machine- and deeplearning development, the available options for code development and a broad support base. A generic guide in developing a platform for AI project development is presented.

Reliable quantification of myocardial sympathetic innervation and regional denervation using [11C]meta-hydroxyephedrine PET.

PURPOSE: Cardiac sympathetic nervous system (SNS) dysfunction is associated with poor prognosis in chronic heart failure patients. This study characterized the reproducibility and repeatability of [11C]meta-hydroxyephedrine (HED) positron emission tomography (PET) quantification of cardiac SNS innervation, regional denervation, and myocardial blood flow (MBF). METHODS: Dynamic HED PET-CT scans were performed 47 ± 22 days apart in 20 patients with stable heart failure and reduced ejection fraction. Three observers, blinded to clinical data, used FlowQuant® to evaluate the test-retest repeatability and inter- and intra-observer reproducibility of HED tracer uptake and clearance rates to measure global (LV-mean) retention index (RI), volume of distribution (VT), and MBF. Values were also compared with and without regional partial-volume correction. Regional denervation was quantified as %LV defect size of values < 75% of the LV-maximum. Test-retest repeatability and observer reproducibility were evaluated using intra-class-correlation (ICC) and Bland-Altman coefficient of repeatability (NPC). RESULTS: Intra- and inter-observer correlations of both VT and RI were excellent (ICC = 0.93-0.99). Observer reproducibility (NPC = 3-13%) was lower than test-retest repeatability (NPC = 12-61%). Both regional (%LV defect size) and global (LV-mean) measures of sympathetic innervation were more repeatable using the simple RI model compared to VT (NPC = 12% vs. 19% and 30% vs. 54%). Using either model, quantification of regional denervation (defect size) was consistently more reliable than the global LV-mean values of RI or VT. Regional partial-volume correction degraded repeatability of both the global and regional VT measures by 2-12%. Test-retest repeatability of MBF estimation was relatively poor (NPC = 30-61%) compared with the RI. CONCLUSIONS: Quantitative measures of global and regional SNS innervation were most repeatable using the simple RI method of analysis compared with the more complex VT. Observer variability was significantly lower than the test-retest repeatability using a highly automated analysis program. These results support the use of the simple RI method for reliable analysis of HED PET images in clinical research studies for future evaluation of new therapies and for risk stratification in patients with heart failure.

Reproducible quantification of cardiac sympathetic innervation using graphical modeling of carbon-11-meta-hydroxyephedrine kinetics with dynamic PET-CT imaging.

BACKGROUND: Graphical methods of radiotracer kinetic modeling in PET are ideal for parametric imaging and data quality assurance but can suffer from noise bias. This study compared the Logan and Multilinear Analysis-1 (MA1) graphical models to the standard one-tissue-compartment (1TC) model, including correction for partial-volume effects, in dynamic PET-CT studies of myocardial sympathetic innervation in the left ventricle (LV) using [11C]HED. METHODS: Test and retest [11C]HED PET imaging (47 ± 22 days apart) was performed in 18 subjects with heart failure symptoms. Myocardial tissue volume of distribution (VT) was estimated using Logan and MA1 graphical methods and compared to the 1TC standard model values using intraclass correlation (ICC) and Bland-Altman analysis of the non-parametric reproducibility coefficient (NPC). RESULTS: A modeling start-time of t* = 5 min gave the best fit for both Logan and MA1 (R2 = 0.95) methods. Logan slightly underestimated VT relative to 1TC (p = 0.002), whereas MA1 did not (p = 0.96). Both the MA1 and Logan models exhibited good-to-excellent agreement with the 1TC (MA1-1TC ICC = 0.96; Logan-1TC ICC = 0.93) with no significant differences in NPC between the two comparisons (p = 0.92). All methods exhibited good-to-excellent test-retest repeatability with no significant differences in NPC (p = 0.57). CONCLUSIONS: Logan and MA1 models exhibited similar agreement and variability compared to the 1TC for modeling of [11C]HED kinetics. Using t* = 5 min and partial-volume correction produced accurate estimates of VT as an index of myocardial sympathetic innervation.

Image-Guided Neurosurgery.

Image-guided surgery provides more precise targeting, is less invasive, and has improved outcomes when compared with conventional surgical approaches. Imaging is used to plan, monitor progress, and assess results. Because no one modality offers real-time physiological and anatomical information, a wide range of imaging modalities are used at each phase of the surgery. This article will discuss how various modalities are used in image-guided neurosurgery for common brain pathologies.

Factors Influencing Non-cardiac Side Effects of Dipyridamole When Used for Myocardial Perfusion Stress Testing.

PURPOSE: This study evaluates whether patient demographic information can be used to predict the non-cardiac side effects experienced during myocardial perfusion imaging (MPI) procedures using dipyridamole. BACKGROUND: Heart disease is a major cause of death in the industrialized world. MPI of coronary blood flow using radiopharmaceuticals is frequently used to assess coronary artery disease. Pharmacological methods can be used to increase coronary blood flow with vasodilators such as dipyridamole or adenosine, or inotropic and chronotropic agents such as dobutamine or arbutamine. The side effects of these agents are recognized, but little is known about the factors that influence their frequency and severity. METHODS: One hundred and nineteen patients scheduled for myocardial perfusion pharmacological stress testing using dipyridamole participated in the study. Patient demographic data, which included age, sex, body mass index (BMI), diabetic status, smoker status, and daily aspirin usage, were collected before the start of the procedure. Patients underwent a 1-day rest and stress MPI procedure. The radiopharmaceuticals used were 99mTc-Myoview or 201Tl. The pharmacological stress procedure used dipyridamole injections based on body weight. Aminophylline was injected at the end of the stress session. Gated single photon emission computed tomography was performed for both rest and stress images. Once the patients completed the procedure, they were given a questionnaire that asked them to report the severity of any side effects experienced from the dipyridamole. Specific data types determined the statistical test best suited for analysis. The Chi-square test was used to evaluate the nominal scale data (sex, diabetic status, aspirin usage, and smoker status), Mann-Whitney test was used to compare nominal scale data and ordinal scale data (side effect severity), Student's t-test r was used for ratio scale data (age, BMI, and percent of population), and multiple linear regression and multiple logistic regression tests were used to evaluate multiple variables. RESULTS: A total of 119 patients were surveyed (58 male, 61 female). The average age was 67.7 years (10.7 year standard deviation). There were no statistically significant differences in the male and female demographics except for daily aspirin usage (more common with males). Headaches were the most common side effect (50% of all patients), followed by dizziness (26%), flushing (24%), chest pain (19%), and nausea (18%). Correlations were found between patients experiencing no side effects with age (r = -0.607) and sex (P = .034); headaches with age (r = -0.706) and BMI (r = 0.464); chest pain with diabetic status (P = .017); dizziness with diabetic status (P = .039); and nausea with age (r = -0.612). CONCLUSION: Side effects of dipyridamole are generally known, but the factors influencing incidence and severity are not. This study has shown that patient demographic information normally gathered before MPI procedures can help determine the frequency and severity of some side effects. Providing more accurate information to a patient on the possible side effects could help reduce patient anxiety and improve patient cooperation.

The perception of children's computer-imaged facial profiles by patients, mothers and clinicians.

OBJECTIVE: To demonstrate the usefulness of a new imaging system for comparing the morphometric bases of children's self-perception of their facial profile with the perceptions of their mothers and treating clinicians. MATERIALS AND METHODS: Rather than choosing among a series of static images, a computer imaging program was developed to elicit a range of acceptable responses or tolerance for change from which a midpoint of acceptability was derived. Using the method of Giddon et al, three profile features (upper and lower lips and mandible) from standardized images of 24 patients aged 8- 15 years were distorted and presented to patients, parents, and clinicians in random order as slowly moving images (four frames per second) from retrusive and protrusive extremes. Subjects clicked the mouse when the image became acceptable and released it when it was no longer acceptable. Subjects responded similarly to a neutral facial profile. RESULTS: Patients and their mothers overestimated the protrusiveness of the mandible of the actual pretreatment profile. Consistent with related studies, mothers had a smaller tolerance for change in the soft tissue profile than the children or clinicians. The magnitudes of the children's self-preference and preferred change in a neutral face were also significantly correlated. Both patients and mothers preferred a more protrusive profile than that of the actual or neutral face for the patient and neutral face. CONCLUSION: Imaging software can be used with children to compare their preferences with those of parents and clinicians to facilitate treatment planning and patient satisfaction.

Second-hand tobacco smoke in Oklahoma: a preventable cause of morbidity and mortality and means of reducing exposure.

Evidence has mounted in recent years establishing second-hand tobacco smoke exposure as a cause of morbidity and mortality in nonsmokers. The ratio of deaths is approximately one nonsmoker dying from illness caused by second-hand smoke exposure for every eight smokers who die from diseases caused by tobacco use. This is equivalent to about 750 nonsmoker deaths each year in Oklahoma caused by exposure to second-hand smoke. This article reviews the components of second-hand smoke, its health effects, its prevalence in Oklahoma, and the means of protecting children and nonsmoking adults from exposure. Oklahoma physicians are encouraged to advise their patients about the harmful effects of second-hand smoke and to actively support public policies that decrease exposure to second-hand smoke in public places and workplaces.

Thinking about things not thought of: why it is important to volunteer and thank those who do.

The director of the dental ethics program at Columbia University School of Dental and Oral Surgery reflects on 9-11. Thinking about the sacrifices of volunteers on the Dental ID Team and the ethics program underscores how dependent our society is on the quiet efforts of a few who volunteer on numerous fronts to support and protect many of the values we hold dear. We, as a society, need to be more cognizant of the importance of these efforts and to give thanks, even where none is expected.