Ambulatory Quality Improvement Despite COVID-19: Blueprint for a Successful System for Continuous Improvement.

ABSTRACT: In this article, we describe our experience developing and implementing a multipronged approach to improve performance across a strategic subset of quality measures within primary care. Detailed techniques include data visualization and analytics, process reengineering, team engagement, visual project management, continuous improvement methods and training, and incentives and recognition. We achieved positive change across 12 high priority measures which we deemed the "High Value Framework (HVF)" by fostering a collaborative, nonpunitive, problem-solving culture. We focused on measures that had the greatest potential for impact from a clinical, reimbursement, and reputational perspective. More importantly, we sustained gains despite the challenges posed by the COVID-19 pandemic, thereby demonstrating programmatic resilience and high process reliability. This systematic approach serves as a practical blueprint for other healthcare entities seeking to navigate the complexities of quality improvement in a dynamic environment. The model provides a strategic framework for prioritizing and standardizing quality measures, effectively engaging stakeholders, and managing organizational change. Our model emerged from a need to address real-world operational challenges, rather than as an academic or theoretical exercise, and was developed independently of existing literature on measure prioritization and standardization at the time of its inception.

Ligament Tension and Balance before and after Robotic-Assisted Total Knee Arthroplasty - Dynamic Changes with Increasing Applied Force.

The optimal force applied during ligament balancing in total knee arthroplasty (TKA) is not well understood. We quantified the effect of increasing distraction force on medial and lateral gaps throughout the range of knee motion, both prior to and after femoral resections in tibial-first gap-balancing TKA. Twenty-five consecutive knees in 21 patients underwent robotic-assisted TKA. The posterior cruciate ligament was resected, and the tibia was cut neutral to the mechanical axis. A digital ligament tensioning tool recorded gaps and applied equal mediolateral loads of 70 N (baseline), 90 N, and 110 N from 90 degrees to full extension. A gap-balancing algorithm planned the femoral implant position to achieve a balanced knee throughout flexion. After femoral resections, gap measurements were repeated under the same conditions. Paired t-tests identified gap differences between load levels, medial/lateral compartments, and flexion angle. Gaps increased from 0 to 20 degrees in flexion, then remain consistent through 90 degrees of flexion. Baseline medial gap was significantly smaller than lateral gap throughout flexion (p <0.05). Increasing load had a larger effect on the lateral versus medial gaps (p <0.05) and on flexion versus extension gaps. Increasing distraction force resulted in non-linear and asymmetric gap changes mediolaterally and from flexion to extension. Digital ligament tensioning devices can give better understanding of the relationship between joint distraction, ligament tension, and knee stiffness throughout the range of flexion. This can aid in informed surgical decision making and optimal soft tissue tensioning during TKA.

Intra-operative laxity and balance impact 2-year pain outcomes in TKA: a prospective cohort study.

PURPOSE: The objective of this study was to determine if intra-operatively measured joint gaps are associated with 2-year pain outcomes in total knee arthroplasty (TKA) and whether balance and laxity windows could be defined throughout flexion to optimize 2-year pain outcomes. Our hypothesis is that intra-operative joint gaps are associated with 2 year post-operative pain outcome. METHODS: A prospective study investigating 310 robotically assisted TKAs was performed. Final intra-operative joint gap data were recorded using a digital tensioner and component alignment data were recorded by the robotics system. Patient demographics and Knee Injury and Osteoarthritis Outcome Score (KOOS) were recorded pre-operatively and KOOS and Hospital for Special Surgery (HSS) satisfaction were recorded at 2 years post-op. A random search Simulated Annealing (SANN) optimisation algorithm was used to determine global optimum laxity and balance windows at different flexion angles which maximized the 2-year KOOS pain scores. The windows were combined to determine the impact of achieving optimal laxity and balance throughout flexion. To improve clinical utility, boundaries identified by the SANN algorithm were rounded to the nearest 0.5 mm before statistical analysis. RESULTS: Laxity and balance windows were defined in extension (Med lax: -2.0 to 2.5 mm, Lat lax: -0.5 to 2.5 mm, Balance: -3.0 to 0.0 mm), mid-flexion (Med lax: -1.0 to 2.5 mm, Lat lax: -0.5 to 3.0 mm, Balance: -2.0 to 2.0 mm), and flexion (Med lax: -2.0 to 3.5 mm, Lat lax: -2.0 to 1.5 mm, Balance: -3.0 to 3.0 mm). When all windows were satisfied, the greatest difference in KOOS pain score was observed (100.0 vs 94.4, p < 0.0001). The highest percentage of knees satisfying the Patient Acceptable Symptom State (PASS) for KOOS pain was also observed in knees which satisfied all windows compared to knees which did not (93% vs 71%, p = 0.0009). The proportion of knees which satisfy the PASS threshold decreased in knees which only satisfied 1-3 (29%) or 4-6 (69%) windows (p ≤ 0.0018). No optimal windows were found between component alignment and KOOS pain outcome (p ≥ 0.1180). High satisfaction was found across all groups (≥ 95%). CONCLUSION: Intra-operatively measured joint gaps are associated with all KOOS sub-score outcomes at 2 years after TKA. Optimal windows for a clinically relevant improvement in post-operative KOOS pain were defined for laxity and balance but not for alignment indicating balance may have a greater impact on outcome than alignment. LEVEL OF EVIDENCE: II.

Unsupervised Pharmaceutical Polymorph Identification and Multicomponent Particle Mapping of ToF-SIMS Data by Non-Negative Matrix Factorization.

Crystal polymorphism of pharmaceutical compounds directly impacts resulting physicochemical characteristics, a critical aspect in active pharmaceutical ingredient (API) production. Tools to characterize and chemically map these polymorphs at the single particle scale remain important to advancing directed manufacture of targeted polymorphs. Here, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed for chemically imaging inkjet printed acetaminophen samples. ToF-SIMS generates large data sets of high spatial resolution images. Extracting relevant data and peaks of interest can be laborious for, and biased by, users. Advances in machine learning approaches have introduced many supervised and unsupervised methods for data analysis. In this study, we apply non-negative matrix factorization (NMF) for the unsupervised analysis of ToF-SIMS chemical image data. More specifically, an expanded variant of NMF, NMFk, was employed to determine the data set's latent dimensionality. NMFk combines the spectral unmixing of traditional NMF with k-means clustering of the resulting factors and an optimization of the reconstruction and clustering. The method was used to identify the number of polymorph phases-and their representative mass spectra-generated from inkjet printed acetaminophen samples. Amorphous, crystalline form I, and crystalline form II polymorphs were observed. The learned polymorph mass spectra were then used to map the learned polymorphs onto subsequent particle samples of acetaminophen. Finally, NMFk also enabled the decomposition of mixed particle samples (i.e., migraine medicine), learning the number of compounds and their composition. The extracted constituent phase mass spectra-representing single compounds-were searched against mass spectral libraries for identification.

Impact of Component Alignment and Soft Tissue Release on 2-Year Outcomes in Total Knee Arthroplasty.

BACKGROUND: The objective of this study was to investigate the impact of alignment and soft tissue release on patient outcomes following total knee arthroplasty (TKA). METHODS: In a multicenter study, soft tissue releases during TKA were prospectively documented in 330 robotic-assisted TKAs. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were captured postoperatively. Delphi analysis was used to determine inlier and outlier component alignment boundaries: Tibia Coronal (TC): ±3°, Femur Coronal (FC): ±3°, Femoral Axial (FA): 3°Int-6°Ext, Hip-Knee-Ankle (HKA): 3°Val-4°Var, and Tibiofemoral Axial (TFA): 3°Int-6°Ext. Kruskal-Wallis analysis of variance tests were used to compare groups. RESULTS: No significant differences were found between any individual or grouped inlier and outlier alignment criterion and KOOS at any timepoint. Outlier alignment frequencies were: TC: 0%, FC: 12%, FA: 8%, HKA: 9%, TFA: 8%, and Any: 23%. Soft tissue releases were performed in 18% of cases. Knees with soft tissue releases reported significantly worse KOOS scores at: 6M: Symptoms (80.0 versus 75.3, P = .03), activities of daily living (ADL) (86.2 versus 80.8, P = .030), quality of life (70.1 versus 60.9, P = .008), 12M ADL (90.0 versus 85.1, P = .023), and 24M ADL (91.9 versus 87.2, P = .016). A higher proportion of patients achieved Minimal Clinically Important Difference for pain at 6 months for those having no releases versus released (92.3% versus 81.0%, P = .021). No significant associations were found between preoperative deformity and preoperative or postoperative KOOS. CONCLUSION: The addition of soft tissue releases after bony cuts is associated with worse KOOS scores out to 2 years and was more prevalent in knees with worse deformity, while no such association was found for alignment.

Improving particle collection efficiency of sampling wipes used for trace chemical detection.

Improvement of the particle collection efficiency of sampling wipes is desirable for optimizing the performance of many wipe-based chemical analysis techniques used for trace chemical screening applications. In this note, commercially available Teflon coated fiberglass and calendered Nomex sampling wipes were modified by mechanically scoring the wipe surface to produce topography that promoted enhanced and localized particle collection. Wipe surface modifications improved particle collection efficiency, relative to unmodified wipes, by factors of 3 to 13 depending on sampling conditions, wipe type, and surface sampled. Improvements were demonstrated for both model polystyrene latex microspheres and inkjet printed explosive particles. The modifications also concentrated particles into pre-defined locations on the wipe which can be engineered to ensure maximum overlap with the thermal desorber of a trace contraband detection system allowing for more effective analysis of collected trace residues.

Improved total knee arthroplasty pain outcome when joint gap targets are achieved throughout flexion.

PURPOSE: Achieving a balanced knee is accepted as an important goal in total knee arthroplasty; however, the definition of ideal balance remains controversial. This study therefore endeavoured to determine: (1) whether medio-lateral gap balance in extension, midflexion, and flexion are associated with improved outcome scores at one-year post-operatively and (2) whether these relationships can be used to identify windows of optimal gap balance throughout flexion. METHODS: 135 patients were enrolled in a multicenter, multi-surgeon, prospective investigation using a robot-assisted surgical platform and posterior cruciate ligament sacrificing gap balancing technique. Joint gaps were measured under a controlled tension of 70-90 N from 10°-90° flexion. Linear correlations between joint gaps and one-year KOOS outcomes were investigated. KOOS Pain and Activities of Daily Living sub-scores were used to define clinically relevant joint gap target thresholds in extension, midflexion, and flexion. Gap thresholds were then combined to investigate the synergistic effects of satisfying multiple targets. RESULTS: Significant linear correlations were found throughout extension, midflexion, and flexion. Joint gap thresholds of an equally balanced or tighter medial compartment in extension, medial laxity ± 1 mm compared to the final insert thickness in midflexion, and a medio-lateral imbalance of less than 1.5 mm in flexion generated subgroups that reported significantly improved KOOS pain scores at one year (median ∆ = 8.3, 5.6 and 2.8 points, respectively). Combining any two targets resulted in further improved outcomes, with the greatest improvement observed when all three targets were satisfied (median ∆ = 11.2, p = 0.002). CONCLUSION: Gap thresholds identified in this study provide clinically relevant and achievable targets for optimising soft tissue balance in posterior cruciate ligament sacrificing gap balancing total knee arthroplasty. When all three balance windows were achieved, clinically meaningful pain improvement was observed. LEVEL OF EVIDENCE: Level II.

Early feeding after percutaneous endoscopic gastrostomy tube placement in patients who require trauma and surgical intensive care: A retrospective cohort study.

BACKGROUND: Critically ill patients experience interruptions in enteral nutrition (EN). For ventilated patients who undergo percutaneous endoscopic gastrostomy (PEG) tube placement, postprocedure fasting times vary from 1 to 24 h depending on the surgeon's preference. There is no evidence to support delayed feeding (DF) after PEG placement. This study's purpose was to determine if there is an increased complication rate associated with early feeding (EF) after PEG. METHODS: 150 adult ventilated patients in the trauma and surgical intensive care unit (TSICU) at a level I trauma center underwent PEG placement in March 2015 through May 2018 by one of six surgical intensivists. Retrospective review revealed variable post-PEG fasting practices: one started EN at 1 h, two started at 4 h, two started at 6 h, and one started at 24 h. Time to initiation of EN and complication rates were assessed. Patients were divided into EF (<4) and DF (≥4 h) groups. RESULTS: Median postprocedure fasting time was 5.5 h. The overall complication rate was 3.3%, with a feeding intolerance rate of 0.7% and aspiration rate of 0%. There was no difference in complication rate for EF (3.1%) as compared with DF (3.4%) (odds ratio, 0.92; 95% CI, 0.10-8.52; P = 0.7). CONCLUSION: Complication rates following PEG placement in ventilated TSICU patients are low and do not change with EF compared with DF. EF is probably safe.

Open port sampling interface mass spectrometry of wipe-based explosives, oxidizers, and narcotics for trace contraband detection.

Rapid screening for chemical traces of explosives and narcotics is widely used to support homeland security and law enforcement. These target compounds span a range of physicochemical properties from organic to inorganic, with preferential ionization pathways in both negative and positive mode operation. Nonvolatile inorganic oxidizers present in homemade fuel-oxidizer mixtures, pyrotechnics, and propellants create a unique challenge to traditional thermal desorption-based technologies. Developments in solid-liquid extraction techniques, specifically, open port sampling interface mass spectrometry (OPSI-MS) provide compelling capabilities to address these hurdles. In this proof of concept study, we investigated the trace detection of wipe-based (i.e., common swipe sampling collection method) explosives, oxidizers, and narcotics using an OPSI source and compact single quadrupole mass analyzer. The liquid dissolution and extraction capabilities of OPSI enabled detection of both traditional military-grade explosives and homemade explosive oxidizers. OPSI-MS sensitivities to a series of seven target compounds from polytetrafluoroethylene (PTFE) coated fiberglass sampling wipes were on the order of several nanograms to sub-nanogram levels. Comparisons with direct solution-based sample analysis enabled quantification of wipe-based sample extraction effects. The system demonstrated quick temporal responses, polarity switching capabilities, and rapid signal decay with minimal carryover, all critical to high throughput screening applications. Coupling traditional swipe sampling with OPSI-MS offers a promising tool for contraband screening applications.

Impact of intra-operative predictive ligament balance on post-operative balance and patient outcome in TKA: a prospective multicenter study.

INTRODUCTION: New technologies exist which may assist surgeons to better predict final intra-operative joint balance. Our objectives were to compare the impact of (1) a predictive digital joint tensioning tool on intra-operative joint balance; and (2) joint balance and flexion joint laxity on patient-reported outcomes. MATERIALS AND METHODS: Two-hundred Eighty patients received posterior cruciate ligament sacrificing TKA with ultra-congruent tibial inserts using a robotic-assisted navigation platform. Patients were divided into those in which a Predictive Plan with a digital joint-tensioning device was used (PP) and those in which it was not (NPP), in all cases final post-operative joint gaps were collected immediately before final implantation. Demographics and KOOS were collected pre-operatively. KOOS, complications and satisfaction were collected at 3, 6 and 12 months post-operatively. Optimal balance difference between PP and NPP was defined and compared using area-under-the-curve analysis (AUC). Outcomes were then compared according to the results from the AUC. RESULTS: AUC analysis yielded a balance threshold of 1.5 mm, in which the PP group achieved a higher rate of balance throughout flexion compared to the NPP group: extension: 83 vs 52%; Midflexion: 82 vs 55%; Flexion 89 vs 68%; Flexion to Extension 80 vs 49%; p ≤ 0.003. Higher KOOS scores were observed in knees balanced within 1.5 mm across all sub-scores at various time points, however, differences did not exceed the minimum clinically important difference (MCID). Patients with > 1.5 mm flexion laxity medially or laterally had an increased likelihood of 2.2 (1.1-4.4) and 2.5 (1.3-4.8), respectively, for failing to achieve the Patient Acceptable Symptom State for KOOS Pain at 12 months. Patient satisfaction was high in both the PP and NPP groups (97.4 and 94.7%, respectively). CONCLUSIONS: Use of a predictive joint tensioning tool improved the final balance in TKA. Improved outcomes were found in balanced knees; however, this improvement did not achieve the MCID, suggesting further studies may be required to define optimal balance targets. Limiting medial and lateral flexion laxity resulted in an increased likelihood of achieving the Patient Acceptable Symptom State for KOOS Pain.

Universal Toxicity Gene Signatures for Early Identification of Drug-Induced Tissue Injuries in Rats.

A new safety testing paradigm that relies on gene expression biomarker panels was developed to easily and quickly identify drug-induced injuries across tissues in rats prior to drug candidate selection. Here, we describe the development, qualification, and implementation of gene expression signatures that diagnose tissue degeneration/necrosis for use in early rat safety studies. Approximately 400 differentially expressed genes were first identified that were consistently regulated across 4 prioritized tissues (liver, kidney, heart, and skeletal muscle), following injuries induced by known toxicants. Hundred of these "universal" genes were chosen for quantitative PCR, and the most consistent and robustly responding transcripts selected, resulting in a final 22-gene set from which unique sets of 12 genes were chosen as optimal for each tissue. The approach was extended across 4 additional tissues (pancreas, gastrointestinal tract, bladder, and testes) where toxicities are less common. Mathematical algorithms were generated to convert each tissue's 12-gene expression values to a single metric, scaled between 0 and 1, and a positive threshold set. For liver, kidney, heart, and skeletal muscle, this was established using a training set of 22 compounds and performance determined by testing a set of approximately 100 additional compounds, resulting in 74%-94% sensitivity and 94%-100% specificity for liver, kidney, and skeletal muscle, and 54%-62% sensitivity and 95%-98% specificity for heart. Similar performance was observed across a set of 15 studies for pancreas, gastrointestinal tract, bladder, and testes. Bundled together, we have incorporated these tissue signatures into a 4-day rat study, providing a rapid assessment of commonly seen compound liabilities to guide selection of lead candidates without the necessity to perform time-consuming histopathologic analyses.

Selection for ancient periodic motifs that do not impart DNA bending.

A ~10-11 bp periodicity in dinucleotides imparting DNA bending, with shorter periods found in organisms with positively-supercoiled DNA and longer periods found in organisms with negatively-supercoiled DNA, was previously suggested to assist in DNA compaction. However, when measured with more robust methods, variation in the observed periods between organisms with different growth temperatures is not consistent with that hypothesis. We demonstrate that dinucleotide periodicity does not arise solely by mutational biases but is under selection. We found variation between genomes in both the period and the suite of dinucleotides that are periodic. Whereas organisms with similar growth temperatures have highly variable periods, differences in periods increase with phylogenetic distance between organisms. In addition, while the suites of dinucleotides under selection for periodicity become more dissimilar among more distantly-related organisms, there is a core set of dinucleotides that are strongly periodic among genomes in all domains of life. Notably, this core set of periodic motifs are not involved in DNA bending. These data indicate that dinucleotide periodicity is an ancient genomic architecture which may play a role in shaping the evolution of genes and genomes.

Detection of fuel-oxidizer explosives utilizing portable capillary electrophoresis with wipe-based sampling.

Portable analytical instrumentation that can provide an alarm indication for the presence of explosives and related components is critical for the identification of explosives-based hazards and threats. Many explosives incident reports involve an inorganic oxidizer-fuel mixture which can include pyrotechnics, fireworks, flash powders, black powders, black powder substitutes, and improvised or homemade explosives. A portable CE instrument with targeted analysis of common inorganic oxidizer ions, for example, chlorate, perchlorate, and nitrate, was used here as a rapid detection platform. Unlike frequently used gas-phase separation and detection instrumentation such as ion mobility spectrometry (IMS), an automated liquid extraction mechanism is required for CE separation using acetate paper sample collection wipes. Target inorganic oxidizers were inkjet-printed onto sample wipes to investigate instrument response relative to the collected analyte spatial distribution. Overall, analyte signal intensities increased with off-center sample deposition due to improved sample extraction from wipes and no change in response was observed for varied array distributions across wipes. The system demonstrated sub 200 ng detection limits for all target analytes, with further improvement when normalizing to an internal standard.

Improved patient access and outcomes with the integration of an eConsult program (teledermatology) within a large academic medical center.

BACKGROUND: Insurance, racial, and socioeconomic health disparities continue to pose significant challenges for access to dermatologic care. Studies applying teledermatology to increase access to underinsured individuals and ethnic minorities are limited. OBJECTIVE: To determine how the implementation of a teledermatology program affects access to health care and patient outcomes. METHODS: A cross-sectional evaluation was performed of all ambulatory dermatology referrals and electronic dermatology consultations (eConsults) at Ohio State University within a 25-month period. RESULTS: Compared with ambulatory referrals, eConsults served more nonwhite patients (612 of 1698 [36.0%] vs 4040 of 16,073 [25.1%]; P < .001) and more Medicaid enrollees (459 of 1698 patients [27.0%] vs 3266 of 16,073 [20.3%]; P < .001). In addition, ambulatory referral patients were significantly less likely to attend their scheduled appointment compared with eConsult patients, as either "no-shows" (246 of 2526 [9.7%] vs 3 of 62 [4.8%]) or cancellations (742 of 2526 [29.4%] vs 8 of 62 [12.9%]; P = .003). There were fewer median days to extirpation for eConsult patients compared with ambulatory referral patients (interquartile range; 80.7 ± 79.8 vs 116.9 ± 86.6 days; P = .004). CONCLUSION: Integrating dermatologic care through a telemedicine system can result in improved access for underserved patients through improved efficiency outcomes.

Discriminative potential of ion mobility spectrometry for the detection of fentanyl and fentanyl analogues relative to confounding environmental interferents.

The opioid crisis and emergence of fentanyl, fentanyl analogues, and other synthetic opioids has highlighted the need for sensitive and robust detection for interdiction at screening points, notably vehicles at border crossings and packages at postal facilities. This work investigates the discriminative potential, sensitivity and specificity, of ion mobility spectrometry (IMS) for the detection of fentanyl and fifteen (15) fentanyl-related compounds (analogues, other opioids, and metabolites) relative to confounding environmental interferents. The environmental background interferent levels, frequency and intensity, were derived from over 10 000 screening samples collected from delivery vehicles entering a federal site. A receiver operating characteristic (ROC) curve methodology was employed to quantify the relationship between sensitivity and specificity for these target compounds on two instruments/configurations. These instrument configurations differed in desorption and drift tube temperatures, reactant ion dopant chemistry, and analysis time. This work identified reduced mobility areas of high interference that resulted in increased false positive rates (FPR), effectively reducing sensitivity (true positive rate: TPR) in those regions. Except for a few target compounds on either of the instruments that exhibited elevated FPRs, detection of fentanyl and fentanyl-related species was achieved at single to tens of nanograms with ≥90% TPR and ≤2% FPR. This work established the importance of systematic environmental background characterization at each specific screening setting in evaluating a platform's true performance.

Imageless, robotic-assisted total knee arthroplasty combined with a robotic tensioning system can help predict and achieve accurate postoperative ligament balance.

BACKGROUND: Achieving balanced gaps is a key surgical goal in total knee arthroplasty, yet most methods rely on subjective surgeon feel and experience to assess and achieve knee balance intraoperatively. Our objective was to evaluate the ability to quantitatively plan and achieve a balanced knee throughout the range of motion using robotic-assisted instrumentation in a tibia-first, gap-balancing technique. METHODS: A robotic-assisted, gap-balancing technique was used in 121 consecutive knees. After resection of the proximal tibia, a computer-controlled tensioning device was inserted into the knee joint and the pre-femoral-resection knee gaps were acquired dynamically throughout flexion under controlled load. Predicted gap profiles were used to plan the femoral implant by adjusting the implant alignment and position within certain boundaries to achieve a balanced knee throughout the range of flexion. Femoral cuts were then made according to this plan using a miniature robotic-assisted cutting guide. The tensioning device used to measure the pre-femoral-resection gaps was then reinserted into the joint to quantify the final gap balance under known tension. The final gap profiles were then compared with the predictive gap plans. RESULTS: The overall root mean square error between the predicted and achieved gaps was 1.3 mm and 1.5 mm for the medial and lateral sides, respectively. Use of robotic assistance resulted in over 90% of knees having mediolateral balance within 2 mm across the flexion range. Gaps at 0° flexion were 2 mm smaller than the gaps at 90°. This difference decreased to less than 1 mm when comparing the tibiofemoral gaps at 10°, 45°, and 90°. CONCLUSIONS: Imageless, robotic-assisted total knee arthroplasty accurately predicts postoperative gaps before femoral resections. This allows surgeons to virtually plan femoral implant alignment and optimize gap balance throughout the range of motion. The accurate prediction of gaps throughout the arc of motion combined with precise, robotically assisted femoral resection produces accurate postoperative ligament balance consistently.

The 17-Gene Genomic Prostate Score Assay Predicts Outcome After Radical Prostatectomy Independent of PTEN Status.

OBJECTIVE: To compare the ability of loss of phosphatase and tensin homolog (PTEN) and Genomic prostate score assay (GPS) in predicting the biochemical-recurrence (BCR) and clinical-recurrence (CR) after radical prostatectomy (RP) for clinically localized prostate cancer (PCa). METHODS: Three hundred seventy seven patients with and without CR were retrospectively selected by stratified cohort sampling design from RP database. PTEN status (by immunohistochemistry [IHC] and fluorescence in situ hybridization [FISH]) and GPS results were determined for RP specimens. BCR was defined as Prostate Specific Antigen (PSA) ≥ 0.2 ng/mL or initiation of salvage therapy for a rising PSA. CR was defined as local recurrence and/or distant metastases. RESULTS: Baseline mean age, PSA, and GPS score for the cohort were 61.1 years, 8 ng/dL, and 32.8. PTEN loss was noted in 38% patients by FISH and 25% by IHC. The concordance between FISH and IHC for PTEN loss was 66% (Kappa coefficient 0.278; P < .001). On univariable analysis, loss of PTEN by FISH or IHC was associated with BCR and CR (P < .05). However, after adjusting for GPS results, PTEN loss was not a significant predictor for CR or BCR (P > .1). The GPS result remained strongly associated with CR and BCR after adjusting for PTEN status (P < .001). PTEN status and GPS results only weakly correlated. GPS was widely distributed regardless of PTEN status indicating the biological heterogeneity of PCa even in PTEN-deficient cases. CONCLUSION: GPS is a significant predictor of aggressive PCa, independent of PTEN status. After adjustment for GPS results, PTEN was not independently associated with recurrence for PCa.

A New Wipe-Sampling Instrument for Measuring the Collection Efficiency of Trace Explosives Residues.

Trace explosives detection, a crucial component of many security screening environments, commonly employs wipe-sampling. Since collection of an explosive residue is necessary for detection, it is important to have a thorough understanding of the parameters that affect the efficiency of collection. Current wipe-sampling evaluation techniques for explosive particles have their limits: manual sampling (with fingers or a wand) is limited in its ability to isolate a single parameter and the TL-slip/peel tester is limited to a linear sample path. A new wipe-sampling instrument, utilizing a commercial off-the-shelf (COTS) 3D printer repurposed for its XYZ stage, was developed to address these limitations. This system allowed, for the first time, automated two-dimensional wipe-sampling patterns to be studied while keeping the force and speed of collection constant for the length of the sampling path. This new instrument is not only capable of investigating the same parameters as current technology (wipe materials, test surfaces, forces of collection, and linear sample patterns), it has added capabilities to investigate additional parameters such as directional wipe patterns (i.e. "L" and "U" shapes, square, and serpentine) and allowing for multiple lines to be sampled during a single collection without the need for adjustments by the user. In this work, parametric studies were completed using 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and the COTS 3D printer for wipe-sampling to establish collection efficiencies for numerous scenarios. Trace explosives detection in field screening environments could be greatly improved with the ability to comprehensively investigate how a wide range of parameters individually affect collection by wipe-sampling. A screener who knows how to properly interrogate any given surface will be much more efficient at detecting trace explosives.

Chromosome architecture constrains horizontal gene transfer in bacteria.

Despite significant frequencies of lateral gene transfer between species, higher taxonomic groups of bacteria show ecological and phenotypic cohesion. This suggests that barriers prevent panmictic dissemination of genes via lateral gene transfer. We have proposed that most bacterial genomes have a functional architecture imposed by Architecture IMparting Sequences (AIMS). AIMS are defined as 8 base pair sequences preferentially abundant on leading strands, whose abundance and strand-bias are positively correlated with proximity to the replication terminus. We determined that inversions whose endpoints lie within a single chromosome arm, which would reverse the polarity of AIMS in the inverted region, are both shorter and less frequent near the replication terminus. This distribution is consistent with the increased selection on AIMS function in this region, thus constraining DNA rearrangement. To test the hypothesis that AIMS also constrain DNA transfer between genomes, AIMS were identified in genomes while ignoring atypical, potentially laterally-transferred genes. The strand-bias of AIMS within recently acquired genes was negatively correlated with the distance of those genes from their genome's replication terminus. This suggests that selection for AIMS function prevents the acquisition of genes whose AIMS are not found predominantly in the permissive orientation. This constraint has led to the loss of at least 18% of genes acquired by transfer in the terminus-proximal region. We used completely sequenced genomes to produce a predictive road map of paths of expected horizontal gene transfer between species based on AIMS compatibility between donor and recipient genomes. These results support a model whereby organisms retain introgressed genes only if the benefits conferred by their encoded functions outweigh the detriments incurred by the presence of foreign DNA lacking genome-wide architectural information.