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To describe longitudinal trends in patients with obesity and Metabolic Syndrome (MetS) undergoing total knee arthroplasty (TKA) and the impact on complications.We identified primary TKA patients between 2006 and 2017 within the National Surgical Quality Improvement Program database. We recorded patient demographics and 30-day complications. We labeled those with an obese Body Mass Index (BMI ≥30), hypertension, and diabetes as having MetS. We used regression to evaluate trends in BMI and complications over time and variables associated with the odds of complication.We identified 270,846 TKA patients, 63.71% of which were obese (n = 172,333), 15.21% morbidly obese (n = 41,130), and 12.37% met the criteria for MetS (n = 33,470). Mean BMI increased by 0.03 per year (0.02-0.05). Despite this, the odds of adverse events in obese patients decreased: major complications by 0.94 (0.93-0.96) and minor complications by 0.94 (0.93-0.95). The proportion of patients with MetS remained stable; however, we found improvements in major (0.94 [0.91-0.97]) and minor complications (0.97 [0.94-1.00]) over time. MetS components (hypertension, diabetes, and BMI ≥40) were associated with major and minor complications in obese patients, while neuraxial anesthesia lowered the odds of major complications in obese patients (0.87 [0.81-0.92]).Mean BMI in primary TKA patients increased from 2006 to 2017. MetS components diabetes and hypertension elevated the odds of complications in obese patients. Rates of complications in patients with obesity and MetS exhibited a longitudinal decline. These findings may reflect increased awareness and improved management of these patients.

Background Reverse shoulder arthroplasty (RSA) is a viable option for posteriorly-eroded B2 glenoids. But little is known in this setting about the effect of baseplate version on impingement on the scapular neck, which affects the risk of notching, the risk of impingement-related instability, and the passive range of motion (ROM). Correcting retroversion with eccentric reaming leads to medialization to achieve full support of the baseplate, bringing the humerus closer to the scapula and potentially increasing impingement on the scapular neck. We hypothesized that correcting retroversion in B2 glenoids would result in increased medialization and worse impingement on the scapular neck. Methods Ten patients with Walch B2 glenoids underwent a simulated RSA. For each patient, a 25 mm baseplate was digitally implanted along the inferior margin of the glenoid, centered anterior-to-posterior, in 0˚ of inclination, with 100% backside contact, with a 36 mm glenosphere and 145˚ neck-shaft angle. Impingement-free ROM was then simulated with 17 different implant arrangements: baseplate version of P (the pathologic version), −15˚, -10˚, −5˚, 0˚, and baseplate lateralization +0, +3mm, +6mm. Two additional simulations consisted of half-wedge baseplates seated at the best fit (matching the paleoglenoid) and 0˚ version. The primary endpoint was external rotation at the side (ERS), based on in-vivo analyses that reveal this as the primary mode of notching and impingement-related instability. Data was analyzed using paired t-test, analysis of variance (ANOVA), and a multivariable regression analysis. Results In every simulation in every patient, correcting retroversion worsened scapular neck impingement with ERS, the primary mode of notching and impingement-related instability. Overall, implantation in retroversion led to 33% more ERS (P = .02). The magnitude of this effect was much greater with medialized glenoids: 100% more ERS for +0 baseplates and 23% more ERS for +6 (P = .008). Half-wedge baseplates resulted in more ERS than +0 baseplates: 2.3x more at 0˚ version (P = .02). Any correction of version resulted in increased medialization (all P Conclusion In B2 glenoids undergoing RSA, correcting the glenoid retroversion with eccentric reaming results in significantly more medialization, worsening scapular neck impingement with ERS. This can increase the risk of notching, may lead to impingement-related instability, and decreases passive ERS. Level of evidence Clinical science study

We cover the operative treatment of a neglected chronic femoral neck fracture nonunion treated at 6 months. We begin with a description of the case and concomitant injuries. The operative portion includes the direct lateral approach with the patient in lateral decubitus position, exposure of the fracture site, osteotomy of the neck, debridement of the nonunion site, broaching, trialing, recognition and treatment of an intraoperative proximal femur fracture using cerclage cabling above and below the lesser trochanter, cementation of final components, and reduction. We conclude with the patient's radiographs at 2 weeks and clinical outcome at 6-week follow-up.

Image guidance (IG) and robotic-assisted (RA) surgery are modern technological advancements that have provided novel ways to perform precise and accurate spinal surgery. These innovations supply real-time, three-dimensional imaging information to aid in instrumentation, decompression, and implant placement. Although nothing can replace the knowledge and expertise of an experienced spine surgeon, these platforms do have the potential to supplement the individual surgeon's capabilities. Specific advantages include more precise pedicle screw placement, minimally invasive surgery with less reliance on intraoperative fluoroscopy, and lower radiation exposure to the surgeon and staff. As these technologies have become more widely adopted over the years, novel uses such as tumor resection have been explored. Disadvantages include the cost of implementing IG and robotics platforms, the initial learning curve for both the surgeon and the staff, and increased patient radiation exposure in scoliosis surgery. Also, given the relatively recent transition of many procedures from inpatient settings to ambulatory surgery centers, access to current devices may be cost prohibitive and not as readily available at some centers. Regarding patient-related outcomes, much further research is warranted. The short-term benefits of minimally invasive surgery often bolster the perioperative and early postoperative outcomes in many retrospective studies on IG and RA surgery. Randomized controlled trials limiting such confounding factors are warranted to definitively show potential independent improvements in patient-related outcomes specifically attributable to IG and RA alone. Nonetheless, irrespective of these current unknowns, it is clear that these technologies have changed the field and the practice of spine surgery. Surgeons should be familiar with the potential benefits and tradeoffs of these platforms when considering adopting IG and robotics in their practices.

Study Design:Retrospective cohort study.Objective:To evaluate inpatient outcomes in dialysis dependent patients undergoing elective cervical spine surgery.Methods:A total of 1605 dialysis dependent patients undergoing elective primary or revision cervical spine surgery for degenerative conditions were identified from the National Inpatient sample from 2002 to 2012 and compared to 1 450 642 nondialysis-dependent patients undergoing the same procedures. The National Inpatient Sample is a de-identified database; thus, no institutional review board approval was needed.Results:Dialysis dependence was associated with higher inpatient mortality rates (7.5% vs 1.9%; P < .001) as well as both major (17.3% vs 0.6%; P < .001) and minor (36.8% vs 10.5%; P < .001) complication rates as compared with nondialysis-dependent patients. Dialysis-dependent patients had substantially increased mean lengths of stay (9.8 days compared with 2.0 days; P < .001) and total hospital charges ($141 790 compared with $46 562; P < .001).Conclusion:Dialysis-dependence is associated with drastically increased complication rates, risk of mortality, and represent a significant financial and psychosocial burden to patients undergoing elective cervical spine surgery. Both surgeons and patients should be aware of these risks while planning elective surgeries.

Background Intramedullary nail (IMN) fixation of metacarpal fractures is an alternative to Kirschner wire (K-wire) fixation. The goal of this study was to compare the biomechanical properties of K-wire fixation with a threaded IMN (InNate; ExsoMed, Aliso Viejo, California). Methods The study design was based on previously described biomechanical models for evaluating metacarpal fractures. Sixteen fresh frozen small finger–matched and ring finger–matched pairs were randomized to either IMN or 0.045 in K-wire fixation after receiving a standardized neck osteotomy. Proper implant placement was confirmed with plain radiographs. Specimens then underwent loading in a 3-point bend configuration. Load to failure (LTF), stiffness, and fracture displacement were recorded. Mechanical failure was defined by a sharp change in the load-displacement curve. Results Age, sex, sidedness (left or right), and digit (ring or small finger) were evenly distributed between groups. The IMN had a significantly higher LTF than K-wires (546 N vs 154 N, P < .001). The K-wire fixation demonstrated plastic deformation between 75 and 150 N. Intramedullary nail stiffness was higher than that of K-wires (155.89 N/mm vs 59.28 N/mm, P < .001). Conclusions When surgical fixation is indicated for metacarpal neck and shaft fractures, the threaded IMN is biomechanically superior to crossed K-wires with the application of 3-point bend.

In reverse shoulder arthroplasty, Inferior tilt was originally promoted to decrease rates of baseplate failure. However, the literature is conflicting regarding the effect of tilt on scapular neck impingement, which has been associated with an increased risk of notching, increased risk of impingement-related instability, and decreased range of motion. We hypothesized that inferior tilt of -10° would lead to increased medialization and increased scapular neck impingement compared with 0° of tilt.Twenty patients without glenoid bone loss undergoing reverse shoulder arthroplasty (RSA) at a single institution underwent computed tomography scans of the entire scapula and proximal humerus for preoperative planning. For each patient, we digitally implanted a 25-mm glenoid baseplate flush with the inferior rim of the glenoid. We then simulated impingement-free range of motion with 16 different implant configurations: glenoid tilt (0° vs. -10°), baseplate lateralization (0 mm vs. +6 mm), glenosphere size (36 mm vs. 42 mm), and neck-shaft angle (135° vs. 145°). The primary endpoint was external rotation with the arm at the side (ERS), which is the primary mode of both notching and impingement-related instability, and the secondary endpoint was adduction (ADD). We recorded the RSA angle, preoperative scapular neck length (SNL), and postoperative SNL. Data were compared by paired t tests and a multivariable regression analysis.In every simulation, inferior tilt led to more impingement on the scapular neck. Inferior tilt of the glenoid component was associated with a mean 27% decrease in impingement-free external rotation (P.01 in all cases) and a mean 32% decrease in impingement-free ADD (P.01 in all cases). Inferior tilt removed 3.2 mm of additional SNL (P.001). Multivariable regression analysis showed that lateralization had the most impact on impingement-free external rotation and ADD (P.001), followed by glenosphere size (P.001), neck-shaft angle (P.001), postoperative SNL (P.001), glenoid tilt (P = .001), inclination (P.001), and RSA angle (P = .023 for ERS and P = .025 for ADD).Relative to 0° of tilt of the baseplate, inferior tilt of -10° was associated with increased scapular neck impingement in ERS and ADD, likely a result of the increased medialization necessary to seat an inferiorly tilted implant, which shortens the scapular neck and brings the humerus closer to the scapula. This scapular neck impingement increases the risk of notching and impingement-related instability.

STUDY DESIGN A retrospective cohort study. OBJECTIVE The aim of this study was to evaluate the effect of metabolic syndrome (MetS) on 30-day morbidity and mortality following elective lumbar spinal fusion. SUMMARY OF BACKGROUND DATA MetS is a variable combination of hypertension, obesity, elevated fasting plasma glucose, and dyslipidemia.MetS has been associated with an increased risk of postoperative morbidity and mortality in multiple surgical settings. To our knowledge, the effect of MetS on 30-day outcomes following elective lumbar spinal fusion has not been well studied. METHODS An analysis of ACS-NSQIP data was performed between 2006 and 2013. Patients undergoing elective posterior lumbar fusion were identified. Emergency procedures, infections, tumor cases, and revision surgeries were excluded. Patients were defined as having MetS if they had a history of hypertension requiring medication, diabetes, and a body mass index (BMI) ≥30 kg/m. RESULTS One thousand five hundred ninety (10.2%) patients with MetS were identified. A mild increase in major (P = 0.040) and minor complications (P = 0.003) in patients with MetS was noted. MetS was associated with increased rates of pulmonary complications (1.9% compared with 1.0%; P = 0.001), sepsis (1.7% compared with 0.9%; P = 0.005), and acute post-op renal failure (0.4% compared with 0%; P

STUDY DESIGN Retrospective cohort study. OBJECTIVE To evaluate hospital outcomes in dialysis-dependent patients undergoing elective lumbar surgeries. SUMMARY OF BACKGROUND DATA Because of their overall poor health status and concomitant comorbidity burden, spinal surgery in dialysis-dependent patients represents a significant challenge to spine surgeons. Large studies evaluating their immediate postoperative outcomes in elective lumbar surgery are lacking. METHODS Utilizing the National Inpatient Sample, an estimated 1834 dialysis-dependent patients undergoing elective lumbar spine surgery for degenerative lumbar conditions were compared to an estimated 2,522,594 non-dialysis-dependent patients undergoing the same procedures between 2002 and 2012. Our primary outcomes measures included postoperative complication rates, hospital length of stay, and total hospital costs. RESULTS Mean age of dialysis-dependent patients was 64.2 years compared to 59.9 in the non-dialysis-dependent cohort (P

Objective The purpose of this study was to investigate potential differences of magnitudes and durations associated with dosed myofascial release (MFR) on human fibroblast proliferation, hypertrophy, and cytokine secretions. Methods Bioengineered tendons (BETs) attached to nylon mesh anchors were strained uniaxially using a vacuum pressure designed to model MFR varying in magnitudes (0%, 3%, 6%, 9%, and 12% elongation) and durations (0.5 and 1-5 minutes). Conditioned media were analyzed for cytokine secretion via protein microarray (n = 2). Bioengineered tendons were weighted and fibroblasts extracted from the BET were assessed for total cell protein and proliferation via double-stranded DNA quantification (n = 5). All data were compared by a 1-way analysis of variance with post hoc Dunnett test and Student t test. Results Changing MFR magnitude and duration did not have an effect on total fibroblast cellular protein or DNA accumulation. However, we observed a stepwise increase in BET weight with higher-magnitude MFR treatments. Longer durations of MFR resulted in progressive increase in the secretions of angiogenin, interleukin (IL)-3, IL-8, growth colony–stimulating factor, and thymus activation–regulated chemokine. Alternatively, increasing strain magnitude induced secretions of IL-1 β , monocyte chemoattractant cytokine, and regulated and normal T cell expressed and secreted chemotactic cytokine. Conclusion Cellular proliferation and hypertrophy were not significantly changed by any treatment. However, the change in total BET dry weight suggests that production of extracellular matrix protein may be up-regulated. Different MFR parameters induce secretions of a unique subset of cytokines and growth factors that can be further enhanced by increasing the magnitude and duration of treatment. If clinically translatable, these results suggest that variations to manual therapy biomechanical parameters may differentially affect physiological responses in vivo.

Skeletal muscle development is influenced by myogenic regulatory factors, including the expression of MyoD and myogenin. Our objective was to use the C2C12 cell culture model to test the hypothesis that both MyoD and myogenin were required for agrin-induced acetylcholine receptor (AChR) clustering and the fusion of myoblasts into myotubes. We induced fusion of myoblasts into myotubes by switching from growth medium (GM) to differentiation medium (DM). During myotube formation AChRs cluster spontaneously, but treatment with motor neuron derived agrin increases clustering of AChRs and other postsynaptic components of the neuromuscular synapse. We examined the normal expression pattern of MyoD and myogenin in C2C12 cell culture using immunofluorescence. MyoD was highly expressed while myoblasts were in GM, but expression declined within 72 hours after cell cultures were switched to DM. Myogenin expression was low in GM, but increased when cell cultures were switched to DM. Next we used antibodies to decrease MyoD and/or myogenin function. Fluorescence microscopy images were captured and then analyzed to assess agrin-induced AChR clustering with or without antibody treatment. Finally we calculated the proportion of nuclei in myotubes and myoblasts by creating digital overlays of phase contrast and DAPI stained microscopy images. This allowed the comparison of myotube formation with or without antibody treatment. We report that antibody to either MyoD or myogenin decreases the frequency of agrin-induced AChR clustering without affecting myotube formation. We conclude that agrin-induced AChR clustering requires both MyoD and myogenin.

Study design Review of the 2011 to 2015 minimum clinically important difference (MCID)-related publications in Spine, Spine Journal, Journal of Neurosurgery-Spine, and European Spine Journal. Objective To summarize the various determinations of MCID and to analyze its usage in the spine literature of the past 5 years in order to develop a basic reference to help practitioners interpret or utilize MCID. Summary of background data MCID represents the smallest change in a domain of interest that is considered beneficial to a patient or clinician. The many sources of variation in calculated MCID values and inconsistency in its utilization have resulted in confusion in the interpretation and use of MCID. Methods All articles from 2011 to 2015 were reviewed. Only clinical science articles utilizing patient reported outcome scores (PROs) were included in the analysis. A keyword search was then performed to identify articles that used MCID. MCID utilization in the selected papers was characterized and recorded. Results MCID was referenced in 264/1591 (16.6%) clinical science articles that utilized PROs: 22/264 (8.3%) independently calculated MCID values and 156/264 (59.1%) used previously published MCID values as a gauge of their own results. Despite similar calculation methods, there was a two- or three-fold range in the recommended MCID values for the same instrument. Half the studies recommended MCID values within the measurement error. Most studies (97.2%) using MCID to evaluate their own results relied on generic MCID. The few studies using specific MCID (MCID calculated for narrowly defined indications or treatments) did not consistently match the characteristics of their sample to the specificity of the MCID. About 48% of the studies compared group averages instead of individual scores to the MCID threshold. Conclusion Despite a clear interest in MCID as a measure of patient improvement, its current developments and uses have been inconsistent. Level of evidence N/A.

Cyclic short-duration stretches (CSDS) such as those resulting from repetitive motion strain increase the risk of musculoskeletal injury. Myofascial release is a common technique used by clinicians that applies an acyclic long-duration stretch (ALDS) to muscle fascia to repair injury. When subjected to mechanical strain, fibroblasts within muscle fascia secrete IL-6, which has been shown to induce myoblast differentiation, essential for muscle repair. We hypothesize that fibroblasts subjected to ALDS following CSDS induce myoblast differentiation through IL-6. Fibroblast conditioned media and fibroblast-myoblast cocultures were used to test fibroblasts' ability to induce myoblast differentiation. The coculture system applies strain to fibroblasts only but still allows for diffusion of potential differentiation mediators to unstrained myoblasts on coverslips. To determine the role of IL-6, we utilized myoblast unicultures ± IL-6 (0–100 ng/ml) and cocultures ± α-IL-6 (0–200 μg/ml). Untreated uniculture myoblasts served as a negative control. After 96 h, coverslips ( n = 6–21) were microscopically analyzed and quantified by blinded observer for differentiation endpoints: myotubes per square millimeter (>3 nuclei/cell), nuclei/myotube, and fusion efficiency (%nuclei within myotubes). The presence of fibroblasts and fibroblast conditioned media significantly enhanced myotube number ( P < 0.05). However, in coculture, CSDS applied to fibroblasts did not reproduce this effect. ALDS following CSDS increased myotube number by 78% and fusion efficiency by 96% vs. CSDS alone ( P < 0.05). Fibroblasts in coculture increase IL-6 secretion; however, IL-6 secretion did not correlate with enhanced differentiation among strain groups. Exogenous IL-6 in myoblast uniculture failed to induce differentiation. However, α-IL-6 attenuated differentiation in all coculture groups ( P < 0.05). Fibroblasts secrete soluble mediators that have profound effects on several measures of myoblast differentiation. Specific biophysical strain patterns modify these outcomes, and suggest that myofascial release after repetitive strain increases myoblast differentiation and thus may improve muscle repair in vivo. Neutralization of IL-6 in coculture significantly reduced differentiation, suggesting fibroblast-IL-6 is necessary but not sufficient in this process.

Detailed rate equation modeling of the laser-excited sodium-molecular nitrogen system was conducted to investigate the applicability of the steady-state three-level model to prediction of sodium laser-induced fluorescence intensities. Redistribution of vibrational population in the nitrogen molecules can, under some conditions, produce a transition to a second-state condition not predicted by the simple three-level model. The feasibility of a major species number density measurement using tracer gas impurity laser-induced fluorescence is discussed in light of the sodium-nitrogen modeling results.

A seroprevalence survey of markers of hepatitis B virus (HBV) infection in children aged 0-16 years was conducted in a mixed-race township in western New South Wales. A total of 408 children were screened representing 95% of the total 0-16-year-old population. Of the Aboriginal subjects, 69% had seromarkers which indicated previous infection with HBV and 14% were hepatitis B surface antigen (HBsAg) seropositive. In the non-Aboriginal subjects the prevalence of seromarkers was 10% with no subjects HBsAg positive. The township provided an ideal setting for studying possible crossinfection from children in a high risk (Aboriginal) population group to children in a low-risk (non-Aboriginal) group. The ratio of children in the high-risk group for HBV infection to those in the low-risk group was approximately 2.7:1. Although HBsAg was highly endemic in the Aboriginal population, the data indicate that little crossinfection has occurred. We conclude that in this and similar mixed-race communities action should be taken to accelerate vaccination programmes aimed at reducing HBV infection among neonates and children in the high-risk groups. This will provide an immediate overall reduction of potential risk to both high-risk and low-risk groups while the issue of universal vaccination is considered further.

The Direct Simulation Monte Carlo (DSMC) computational technique was used to simulate the interaction between a carbon monoxide jet and a high velocity freesteam of oxygen atoms oriented at 90° to the jet flow axis at 150km simulated altitude. The results of a study to characterize the sensitivity of predicted CO vibrational excitation to the vibrational excitation cross section and the nozzle exit plane profile are presented in this paper. A literature value of the vibrational excitation cross section is used as a baseline, and comparative simulations are made for cross sections that vary around that value. Similarly, the nozzle exit plane profile is varied from a “flat” profile to a fully developed laminar boundary layer profile to obtain sensitivities to the jet inflow startline. SMILE, a software system based on the DSMC method, developed at the Institute of Theoretical and Applied Mechanics, Novosibirsk, Russia, has been utilized for this study. The results demonstrate a generally linear scaling of the vibrational excitation with cross section, except for cross sections that produce excitation rates in excess of the VHS gas kinetic rate. The jet exit‐plane boundary layer profile was found to be a factor in the amount of CO excited state produced in the interaction region.

PURPOSE. To explore the use of helical CT-derived Quantitative Textural Analysis (QTA) parameters in identifying elevated rates of intrachromosomal copy number aberrations in mPC and secondarily in revealing post-treatment QTA prognostic markers. MATERIALS AND METHODS. Metastatic tumor sites were biopsied and molecularly profiled in a cohort patients with mPC (n=35). 85% of the cohort had 1-3 previous treatment regimens, and the remaining 15% had 4-6. Intrachromosal copy number were assessed by CGH in tumor specimens, and patients were treated with commercially available cytotoxic regimens based on these individual molecular profiling results1. Patients with available pre-biopsy transverse abdominal portal-venous phase CT scans were obtained for retrospective analysis (n=17). Analysis of pre-biopsy pancreas imaging was performed by drawing regions of interest around the primary pancreas adenocarcinoma (n=15) and the normal pancreas tissue when available (n=12). Two patients did not have any quantifiable imaging due to surgery or local structural obfuscation and were not included in our cohort. There were 9 males and 6 females all with stage IV cancer from 34 - 71 years old (median 59). QTA parameters were derived using the TexRAD platform at texture filtering densities of medium (3 pixels) and coarse (5 pixels). There values were compared to intrachromosomal copy number aberrations per tumor and overall survival post-treatment using a Spearman's rank correlation coefficient. RESULTS. Intrachromosomal copy number aberrations (median: 14; range: 5 - 52) were negatively correlated with the kurtosis value of the primary tumor mass (median: -0.146; range: -0.810 - 0.633) using medium texture filtering (p = 0.034, n = 15). Secondary analysis of the normal pancreas with coarse texture filtering yielded a correlation between reduced overall survival time post-treatment and increasing entropy (p = 0.0014, n = 12). Using entropy as a cutoff value (median: 4.165; range 2.686 - 4.891), median overall survival was greater in the entropy < 4.165 group versus the entropy > 4.165 group (6.1 v 2.0 months, respectively; hazards ratio [HR] = 11.5; 95% CI 1.36 - 97.4; p = 0.025, n = 12). Median survival for the entire cohort was 120 days and ranged from 1 day to 372 days post-treatment. CONCLUSION. This exploratory study with admittedly limited sample size raises interesting questions about the use of QTA parameters as diagnostic tools and/or biopsy adjuncts in assessing pancreatic adenocarcinoma susceptibility to commercially available cytotoxics. Secondarily, entropy, a potential marker of heterogeneity and inflammation in the normal pancreas, represents an intriguing possibility for gauging prognosis in mPC. (Clinical trial supported by a grant from the SU2C/AACR-pancreatic dream team) REFERENCES. 1. Ramanathan RK et al AACR Annual Meeting. LB-221. 2012. Citation Format: David H. Campbell, Michael Barrett, Ramesh K. Ramanathan, Daniel D. Von Hoff, Ronald Korn. Quantitative Textural Analysis (QTA) in CT imaging: Identifying markers for genetic instability and overall survival in cohort of previously treated metastatic pancreatic cancer (mPC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1885. doi:10.1158/1538-7445.AM2014-1885

Background Non-invasive characterization of a tumor's molecular features could enhance treatment management. Quantitative computed tomography (CT) based texture analysis (QTA) has been used to derive tumor heterogeneity information, and the appearance of the tumors has been shown to relate to patient outcome in non-small cell lung cancer (NSCLC) and other cancers. In this study, we examined the potential of tumoral QTA to differentiate K-ras mutant from pan-wildtype tumors and its prognostic potential using baseline pre-treatment non-contrast CT imaging in NSCLC. Methods Tumor DNA from patients with early-stage NSCLC was analyzed on the LungCarta Panel. Cases with a K-ras mutation or pan-wildtype for 26 oncogenes and tumor suppressor genes were selected for QTA. QTA was applied to regions of interest in the primary tumor. Non-parametric Mann Whitney test assessed the ability of the QTA, clinical and patient characteristics to differentiate between K-ras mutation from pan-wildtype. A recursive decision tree was developed to determine whether the differentiation of K-ras mutant from pan-wildtype tumors could be improved by sequential application of QTA parameters. Kaplan-Meier survival analysis assessed the ability of these markers to predict survival. Results QTA was applied to 48 cases identified, 27 had a K-ras mutation and 21 cases were pan-wildtype. Positive skewness and lower kurtosis were significantly associated with the presence of a K-ras mutation. A five node decision tree had sensitivity, specificity, and accuracy values (95% CI) of 96.3% (78.1–100), 81.0% (50.5–97.4), and 89.6% (72.9–97.0); respectively. Kurtosis was a significant predictor of OS and DFS, with a lower kurtosis value linked with poorer survival. Conclusions Lower kurtosis and positive skewness are significantly associated with K-ras mutations. A QTA feature such as kurtosis is prognostic for OS and DFS. Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with patient survival.

An AFRL/NRL team has recently been selected to develop a scalable, parallel, reacting, multidimensional (SUPREM) Direct Simulation Monte Carlo (DSMC) code for the DoD user community under the High Performance Computing Modernization Office (HPCMO) Common High Performance Computing Software Support Initiative (CHSSI). This paper will introduce the JANNAF Exhaust Plume community to this three-year development effort and present the overall goals, schedule, and current status of this new code.

OBJECTIVE To evaluate the uptake of hepatitis B vaccination by staff of a metropolitan district general hospital and associated community health service in order to determine if the existing vaccination program was adequate. DESIGN, SETTING AND PARTICIPANTS A cross-sectional survey of all 1464 staff of a 304-bed district general hospital and associated community health service, serving a population of approximately 240,000 people in a middle socioeconomic area of northern Sydney, by means of a self-reported anonymous questionnaire. RESULTS The overall response rate was 56.4%, with 61.9% of high-risk and 48.7% of low-risk staff responding to the survey. The overall vaccination rate was 55.8%. Of high-risk respondents, 70.7% had been or were in the process of being vaccinated, compared with 29.4% of low-risk respondents. Of those already vaccinated, only 45.9% had subsequently been tested for antibody to hepatitis B surface antigen (anti-HBs); 12% of this group did not know whether their response to the vaccine had been adequate and 18% reported being advised to have another anti-HBs test later. Vaccination rates were higher in younger staff (68.7% of 20-29-year-olds) than in older staff (42.7% of 50-59-year-olds). There was no significant difference in vaccination rates between men (55.6%) and women (55.8%). Vaccination rates for doctors, dentists and nurses were 69%, 80% and 74.6%, respectively. CONCLUSION The vaccination rate among high-risk staff is suboptimal: more than half did not know whether their vaccination had induced a suitable level of antibodies; more than 10% had been vaccinated more than five years previously; and 5% had not completed the full course of three injections. High-risk staff should be targeted in future vaccination programs.

Rats tend to prefer flavors previously consumed under low deprivation to flavors previously consumed under high deprivation (Capaldi & Myers, 1982). We attempted to distinguish among possible associative explanations by determining whether this conditioning phenomenon was based upon conditioned preferences, conditioned aversions, or both. We compared preference for flavors presented exclusively under either high or low deprivation with preference for a neutral flavor. In Experiments 1A and 1B the neutral flavor was one that had been randomly paired with both high and low deprivation, whereas in Experiments 2 and 3 the neutral flavors had not been associated with either high or low deprivation. Our results strongly suggest that this conditioning phenomenon is based upon an actual increase in preference for the flavor consumed under low deprivation rather than on any form of aversion conditioning.

108, March 1972, Air Force Flight Dynamics Lab., Wright-Patterson Air Force Base, Ohio. Harder, R. L. and Rodden, W. P., "Kernel Function for Nonplanar Oscillating Surfaces in Supersonic Flow," Journal of Aircraft, Vol. 8, No. 8, Aug. 1971, pp. 677-679. Cunningham, A. M., Jr., "The Application of General Aerodynamic Lifting Surface Elements to Problems in Unsteady Transonic Flow," CR-112264, Feb. 1973, NASA. Multhopp, H., "Methods for Calculating the Lift Distribution of Wings," (Appendix I, Contributed by W. Mangier), Rept. Aero-2353, January 1950, Royal Aircraft Establishment, Farnborough, Great Britain.

In three experiments experience with shock was shown to reduce the effectiveness of shock as a reinforcer or motivator. In Experiment 1 rats were given signaled shock in a box separate from the runway where they were subsequently punished. These rats were less suppressed by shock punishment than rats that had no previous shock experience. In Experiment 2 preshocked rats were less suppressed by punishment and were slower to learn an escape-avoidance response than nonpreshocked rats, whether the preshock was signaled or unsignaled. In Experiment 3 as number of CS-shock pairings increased, fear of the CS decreased as did fear of the context. These results suggest that some central adaptation process produced by experience with shock reduces the effectiveness of shock as a reinforcer whenever shock is used repeatedly. This is independent of other effects, such as context blocking, that can affect responding after shock preexposure.

In five experiments, rats’ preference for a flavor was greater if the flavor had previously been consumed under low rather than high deprivation. This preference was conditioned in as few as three flavor-deprivation pairings (Experiment 1), and persisted through 28 test days, half under each deprivation level (Experiment 2). Rats never preferred the flavor associated with high deprivation even when calories were increased by giving 40 ml of 8% sucrose or when caloric density was increased to the equivalent of 20% sucrose. The preference for the low-deprivation flavor was greater when saccharin solutions were used rather than sucrose solutions, but the preference did emerge when sucrose solutions were used as testing proceeded and when a lower concentration of sucrose was used. We suggest that these preferences may be a result of flavor-taste associations rather than associations between flavors and postingestive consequences, and that the taste of the solutions under low deprivation is preferred to the taste under high deprivation.

In three experiments rats were given go no go discrimination training with flavors as cues and sucrose and quinine as differential consequences. Following discrimination training conditioned preference for the flavor cues was assessed. Go no go discrimination was used as a measure of differential consequence expectancies associated with the two flavor cues. In Experiments 1 and 2 rats did acquire specific flavor-consequence expectancies as evidenced by successful go no go discrimination learning mediated by flavor cues. Subjects also acquired a conditioned preference for the sucrose-paired flavor. In Experiment 3 the predictive relationship between flavor cues and consequences was explicitly reversed between two separate training contexts. Subjects were able to learn this conditional go no go discrimination, suggesting acquisition of context-specific flavor-consequence expectancies, but no context-specific conditioned preference was observed. This suggests the operation of different conditioning mechanisms in simple expectancy learning and preference conditioning. These data confirm that rats can use flavor cues as discriminative stimuli for instrumental behavior when consequences are like those used in preference/aversion conditioning.

In “irrelevant incentive learning” information stored about an incentive when it is not desired is used later when the incentive is desired. In “habit learning” responses learned under one motive state continue to be made under a new motive state even though they produce goal events that are not appropriate to that motive state. Experiment 1 showed that both types of learning occur simultaneously whether flavor or texture cues are used and whether or not position is also a relevant cue. Thus, contrary to previous suggestions, irrelevant incentive learning is not limited to interoceptive cues, nor is habit learning limited to exteroceptive cues. In both Experiments 1 and 2 it was also shown that motivation affects what is learned as well as affecting current performance. This contrasts with views of motivation as solely a determinant of performance.

The structure of the flow of argon through a 2-cm-long, 4-mm-diam tube, around the tube lip, and into vacuum has been investigated using the Direct Simulation Monte Carlo technique. Two lip geometries have been compared, and the shape and thickness of the lip were found to have a significant influence on the flow field structure and the total flux into the backflow. The effects of the temperature and scattering characteristics of the front lip surface were investigated and found to affect the backflow only for certain lip shapes. The number density and temperature of the gas were also found to have a significant effect on the backflow due to changes in the collisional processes in the expansion flow, which affects the freezing of the parallel component of the random motion of the gas. HE expansion of gases out of a rocket nozzle or out- gassing orifice into a low-density background is an impor- tant problem with importance to spacecraft contamination, heat transfer, and infrared sensor interference. The expansion of gases around the nozzle lip and into the region upstream of the nozzle exit plane, usually referred to as the backflow region, is a particularly complex gas dynamic problem. It has been recognized for many years*~6 that the expansion of the subsonic and lower Mach number supersonic regions of the boundary layer around a nozzle lip can produce significant flux into the high-angle backflow region not predicted by the conventional Prandtl-Meyer uniform supersonic flow analysis. It has recently been recognized that nonequilibrium effects,7 due to the rapid rarefaction of the flow out of a nozzle exiting to vacuum or near vacuum, can affect the structure of the flow around a nozzle lip. Consequently, accurate modeling of the flowfield around a nozzle lip and into the high-angle backflow region cannot be obtained using standard equilibrium gas dynamic models. The Direct Simulation Monte Carlo (DSMC) modeling technique,8 which models a gas flow by following some representative number of molecules through simulated collisions, does account for nonequilibrium effects, and is essentially the only technique presently available for accurate prediction of these flows. The shape of the nozzle lip may play an important role in determining the flux into the backflow. Pipes et al. 9 observed some effects of nozzle-lip shape on the flowfield at the exit plane for carbon dioxide and nitrogen expansions from small nozzles, with a pronounced dependence of the effect on the level of condensation in the flow. Direct evidence of lip shape effects on flow into the backflow region was observed by Chirivella10 for pure nitrogen flows. Hueser et al. 11 used the DSMC technique to study the detailed flowfield around the nozzle lip for conditions simulating the inertial upper stage IUS motor at 282-km altitude. They found large differences between the flowfield predicted by the DSMC technique and that predicted by the equilibrium Method of Characteristi cs technique. They modeled a nozzle lip with finite thickness, but investigated only one lip shape and one lip thickness for one set of initial flow conditions. The results of a detailed DSMC theoretical analysis of the effects of lip shape and lip thickness on the flowfield around the lip of a nozzle with zero half angle (tube) will be presented in this paper. In addition, the effects of upstream conditions (gas density and temperature), front lip surface temperature, and front lip surface accommodation coefficient on the backflow structure have been investigated and will be de- scribed. As will be shown, the degree of translation nonequi- librium in the gas expansion, which is dependent on the gas density and temperature, can significantly affect the structure and degree of backflow. In addition, translation nonequi- librium processes interact with the different lip shapes and thicknesses in a nonsimple manner.

In three experiments, counterconditioning was found to reduce fear less effectively than extinction. In Experiments 1 and 2, the resistance to extinction of avoidance was greater if food was given during extinction of fear to the CS than if no food was given, even when exposure to the CS and numbers of food and no food confinement trials were equated. It is suggested that these results could be attributed to contextual control of fear extinction by the food cue and/or to frustration produced by removing food for the counterconditioning group. Experiment 3 also found counterconditioning to be less effective than extinction and provided evidence that this difference occurs because of contextual control of fear extinction by the food cue. Measuring conditioned suppression of licking, in a test with no food present, less fear was shown if no food had been present during fear extinction, and greater fear was shown if no food had been present during fear conditioning. These results indicate that food is an important part of the context controlling fear and fear extinction. It is suggested that there may be no unique counterconditioning process. Rather, when counterconditioning procedures are employed, rules governing interference paradigms in general may apply. Thus, in a test for fear following counterconditioning, fear will be shown to the extent the test situation is similar to that in which fear conditioning occurred rather than that in which fear reduction occurred.

In four experiments we showed that rats prefer a flavor associated with a delayed edible consequence if the delayed consequence contains calories; the greater the number of calories, the greater the preference. We obtained conditioned preferences with delayed consequences of dextrose plus quinine, 8% polycose, 8% sucrose, 10 g of high fat mash, and 14 g of lab chow. No conditioned preferences were obtained with delayed consequences of saccharin, 10 g of low fat mash, 1% polycose, or 1% sucrose. Thus, it seems that flavor preferences based on delayed caloric consequences occur only if there are appreciable calories in the consequence.

A full vibrational–rotational level rate equation model has been used to investigate the application of laser-induced fluorescence techniques to number density measurements of hydroxide in a combustion environment. The extent of deviation of the population in the laser-pumped vibrational and rotational levels from the-two-level model prediction, due to collisional exchange mechanisms, was investigated for a range of pressures, temperatures, laser powers, and collisional exchange rates.

There is a great deal of interest in obtaining a better understanding of the important chemical mechanisms occuring in solid propellant flames [1]. Some of the best methods of obtaining this chemical information are the recently developed laser-based combustion diagnostics, such as laser-induced fluorescence (LIF)(e.g., [2]). Solid propellant flames are quite complex, so a complete description of the flame down to the level that simple flames have been analyzed is not feasible at present. What is needed is a better understanding of the flame structure and major reaction pathways in solid propellant flames as a function of pressure and propellant composition. The distribution of radicals such as CN, NH, and OH, as seen in laser-induced fluorescence, will be a key part of this improved understanding of solid propellant flame chemistry.

A seroepidemiological study of markers of infection with hepatitis B virus was conducted in Brewarrina, a mixed-race township in north-western New South Wales. Six hundred and forty-three subjects, who represented 41.5% of the town's population, were screened for a range of serological markers of hepatitis B virus infection. Of the Aboriginal subjects, 72% had markers which indicated previous infection with hepatitis B virus, with 19.2% of subjects being identified as hepatitis B surface antigen (HBsAg)-seropositive. In the non-Aboriginal subjects, the prevalence of infection with markers of hepatitis B virus was 13.1%, with 2.2% of subjects being HBsAg-seropositive. The marker prevalences for Aboriginal and non-Aboriginal subjects in the 15- to 19-year-old age-group were 86.7% and 28%, respectively. The prevalence of hepatitis B virus infection in the total non-Aboriginal sample was higher than it is in the general Australian blood-donor population. The extent to which hepatitis B virus infection may result from cross-infection between coexisting "high-risk" and "low-risk" population groups is speculative. Furthermore, the risk of infection to non-Aborigines is unlikely to be spread evenly across the non-Aboriginal community. The cost of vaccine remains high, and until further data become available, mass vaccination of the population probably is not warranted. Initially, control measures should concentrate on the reduction of hepatitis B virus infection in the Aboriginal population and in non-Aboriginal households which contain a HBsAg-seropositive member.

We investigated in rats whether giving a sweet substance following a food (a 'dessert') would reinforce a preference for that food. The sweet substance had the reverse effect--rats preference for a flavor decreased if the flavor was given in a food preceding a sweet substance (saccharin or sucrose). If the substances were given in the reverse order, so the sweet substance preceded the food, the rats preferred a sweet substance that had been followed by food to one that had not been followed by food. We suggested two hypotheses to account for the data. Perhaps the sweet substance elicits a negative reaction that is unpleasant unless food is given. Thus, food following a sweet substance is reinforcing, while a sweet substance following food is not. A not incompatible alternative is that anticipatory contrast or comparison effects are involved. Assuming the sweet substance is preferred to the non-sweet, following food by a sweet substance could make the food less valued (anticipatory negative contrast), whereas following a sweet substance by food could make the sweet substance more valued (anticipatory positive contrast).

The laser-induced fluorescence technique was investigated via detailed rate equation modeling of hydroxide in a simulated premixed atmospheric methane-air flame environment. The extent of deviation from the simple two-level model, due to buildup of population in the vibrational bath levels from quenching and vibrational exchange collisions, was addressed as were the effects of variation in the magnitude of the collision -al energy exchange rate constants. Typical results show a breakdown in the two-level model on a nanosecond time scale and indicate that OH number density measurements with accuracies better than an order of magnitude will require (1) better information on detailed quenching rates and (2) laboratory measurements which address the time history of the fluorescent signal on a nanosecond time scale.

The application of laser-induced fluorescence (LIF) to the study of high pressure solid propellant flames is described. The distribution of the OH and CN radicals was determined in several solid propellant flames at pressures up to 3.5 MPa. The greatest difficulty in these measurements was the separation of the desired LIF signals from the large scattering at the laser wavelength from the very optically thick propellant flames. Raman experiments using 308-nm excitation were also attempted in the propellant flames but were unsuccessful due to LIF interferences from OH and NH.