Generalizable turbulent flow forecasting for adaptive optics control.

In this work, we characterize the capability of artificial neural network predictive models for generalizable turbulence forecasting, particularly for use in predictive adaptive optics (AO) applications. Predictive AO control, which utilizes future state predictions of an optical wavefront propagated through a turbulent medium to drive correction, is a promising technology for optical propagation in high-disturbance and low-signal environments. The dynamics describing the evolution of turbulent flow can vary greatly. Accordingly, a generalizable approach to turbulence forecasting has key benefits in allowing for prediction across a range of conditions, thus enabling continuous predictive AO operation in dynamic environments and having reduced sensitivity to changes in conditions. We present a model for generalizable turbulence forecasting, which demonstrated consistent high performance over a range of compressible flow conditions outside those included in the training sample, with only a minimal increase in prediction error compared with a hypothetical baseline model, which assumes perfect a priori characterization. These results demonstrate a clear ability to extract useful dynamics from a limited domain of turbulent conditions and apply these appropriately for forecasting, which could inform future design of predictive AO systems.

Dynamic mode decomposition based predictive model performance on supersonic and transonic aero-optical wavefront measurements.

Air density variations around an airborne directed energy system distort a beam's wavefront, resulting in degraded performance after propagation into the far field. Adaptive optics (AO) can be used to correct for these rapidly evolving aero-optical aberrations; however, in some conditions, the inherent latency between measurement and correction in state-of-the-art AO systems results in significantly reduced performance. Predictive AO control methods utilize future state predictions to compensate for rapidly evolving distortions and are promising techniques for mitigating this limitation. This paper demonstrates an application of the dynamic mode decomposition (DMD) method on turbulent boundary layer wavefront data from supersonic and transonic wind tunnel flow from the Air Force Research Laboratory's Aero-Effects Laboratory. DMD is a lightweight algorithm used to isolate spatiotemporal patterns in a dataset into physically meaningful modes with associated dynamics, which were used to predict future states from a given wavefront. This method showed notable improvements in simulated wavefront correction, providing a reduction of residual wavefront distortion, measured as root mean square over the aperture, by up to 25.4% over a simulated latency model, which could accordingly result in higher laser system performance.

Esrrb-Cre excises loxP-flanked alleles in early four-cell embryos.

Among transgenic mice with ubiquitous Cre recombinase activity, all strains to date excise loxP-flanked (floxed) alleles either at or before the zygote stage or at nondescript stages of development. This manuscript describes a new mouse strain, in which Cre recombinase, integrated into the Esrrb locus, efficiently excises floxed alleles in pre-implantation embryos at the onset of the four-cell stage. By enabling inactivation of genes only after the embryo has undergone two cleavages, this strain should facilitate in vivo studies of genes with essential gametic or zygotic functions. In addition, this study describes a new, highly pluripotent hybrid C57BL/6J x 129S1/SvImJ mouse embryonic stem cell line, HYB12, in which this knockin and additional targeted alleles have been generated.

Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice.

BACKGROUND & AIMS: Augmenter of liver regeneration (ALR, encoded by GFER) is a widely distributed pleiotropic protein originally identified as a hepatic growth factor. However, little is known about its roles in hepatic physiology and pathology. We created mice with liver-specific deletion of ALR to study its function. METHODS: We developed mice with liver-specific deletion of ALR (ALR-L-KO) using the albumin-Cre/LoxP system. Liver tissues were collected from ALR-L-KO mice and ALR(floxed/floxed) mice (controls) and analyzed by histology, reverse-transcription polymerase chain reaction, immunohistochemistry, electron microscopy, and techniques to measure fibrosis and lipids. Liver tissues from patients with and without advanced liver disease were determined by immunoblot analysis. RESULTS: Two weeks after birth, livers of ALR-L-KO mice contained low levels of ALR and adenosine triphosphate (ATP); they had reduced mitochondrial respiratory function and increased oxidative stress, compared with livers from control mice, and had excessive steatosis, and hepatocyte apoptosis. Levels of carbamyl-palmitoyl transferase 1a and ATP synthase subunit ATP5G1 were reduced in livers of ALR-L-KO mice, indicating defects in mitochondrial fatty acid transport and ATP synthesis. Electron microscopy showed mitochondrial swelling with abnormalities in shapes and numbers of cristae. From weeks 2-4 after birth, levels of steatosis and apoptosis decreased in ALR-L-KO mice, and numbers of ALR-expressing cells increased, along with ATP levels. However, at weeks 4-8 after birth, livers became inflamed, with hepatocellular necrosis, ductular proliferation, and fibrosis; hepatocellular carcinoma developed by 1 year after birth in nearly 60% of the mice. Hepatic levels of ALR were also low in ob/ob mice and alcohol-fed mice with liver steatosis, compared with controls. Levels of ALR were lower in liver tissues from patients with advanced alcoholic liver disease and nonalcoholic steatohepatitis than in control liver tissues. CONCLUSIONS: We developed mice with liver-specific deletion of ALR, and showed that it is required for mitochondrial function and lipid homeostasis in the liver. ALR-L-KO mice provide a useful model for investigating the pathogenesis of steatohepatitis and its complications.

The epidemiology of professional ice hockey injuries: a prospective report of six NHL seasons.

BACKGROUND: There is a paucity of literature examining injury and illness rates in men's professional ice hockey. This study aimed to determine injury and illness rates in the NHL over six seasons, and identify predictors of injury-related time loss in this population. METHODS: This study involved an inclusive cohort of hockey players from all NHL teams competing in the 2006-2007 through 2011-2012 seasons. A standardised electronic injury surveillance system was used to report injury and illness events. The primary outcome was regular season and postseason time-loss injury/illness. The secondary outcome was man-games lost from the competition. RESULTS: On the basis of the estimated athlete exposures (AEs), the overall regular season incidence density was 15.6 injuries/1000 AEs and 0.7 illnesses/1000 AEs. Based on recorded time on ice, the injury rates were roughly threefold higher at 49.4 injuries/1000 player game-hours and 2.4 illnesses/1000 player game-hours. There was a reduction in injury rates over the 6-year period, with the greatest reduction between the 2007-2008 and 2008-2009 seasons. Multivariate predictors of time loss greater than 10 days were being a goalie (OR=1.68, 95% CI 1.18 to 2.38), being injured in a road game (OR=1.43, 95% CI 1.25 to 1.63) and the mechanism of injury being a body check (OR=2.21, 95% CI 1.86 to 2.62). CONCLUSIONS: There was an overall reduction in the time-loss injury and illness rates over six seasons. Being a goaltender, being injured on the road and being injured by a body check were the risk factors for time loss greater than five 'man games'.

Aseptically processed and chemically sterilized BTB allografts for anterior cruciate ligament reconstruction: a prospective randomized study.

PURPOSE: To compare the clinical outcomes of bone-patellar tendon-bone (BTB) allografts processed via a novel sterilization system with the traditional aseptically processed BTB allografts for anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 67 patients undergoing ACL reconstruction at 6 independent investigation sites were randomized into one of two intervention groups, BioCleanse-sterilized or aseptic BTB allografts. Inclusion criteria included an acute, isolated, unilateral ACL tear, and exclusion criteria included prior ACL injury, multi-ligament reconstruction, and signs of degenerative joint disease. Post-op examiners and patients were blinded to graft type. Patients were evaluated at 6, 12, and 24 months. Clinical outcomes were compared using the IKDC, a KT-1000 knee arthrometer, level of effusion, and ranges of motion (ROM). RESULTS: After randomization, 24 patients received aseptic BTB allografts and 43 patients received BioCleanse-sterilized allografts. Significant improvement in IKDC scores (P < 0.0001) as well as KT-1000 results (P < 0.0001) was noted over the 24-month period for both groups. IKDC or KT-1000 results were not significantly different between groups at any time point. Active flexion ROM significantly improved from pre-op to 24-month follow-up (P < 0.0001) with no difference between groups at any time point. Active extension ROM did not differ significantly between the two groups. CONCLUSIONS: These results indicate that the sterilization process, BioCleanse, did not demonstrate a statistical difference in clinical outcomes for the BTB allograft at 2 years. The BioCleanse process may provide surgeons with allografts clinically similar to aseptically processed allograft tissue with the benefit of addressing donor-to-recipient disease. LEVEL OF EVIDENCE: II.

Viscosupplementation treatment of arthritis pain.

With the aging of the baby boomer generation, the number of patients with osteoarthritis (OA) is expected to swell, posing treatment challenges. Viscosupplementation, in which hyaluronic acid (HA) is injected into the knee joint, has evolved into an important part of our current therapeutic regimen in addressing the patient with knee pain due to OA. Although suffering from lack of an "evidence-based" approach, and largely funded by industry, there is a growing body of outcome data demonstrating the efficacy of HA in decreasing pain and improving function in patients with knee OA, although no evidence indicates that HA is in any way chondroprotective. The clinical success of HA has led to the ongoing introduction of various forms of HA, although little data are available to justify one over the other.

Human IL-12 p40 as a reporter gene for high-throughput screening of engineered mouse embryonic stem cells.

BACKGROUND: Establishing a suitable level of exogenous gene expression in mammalian cells in general, and embryonic stem (ES) cells in particular, is an important aspect of understanding pathways of cell differentiation, signal transduction and cell physiology. Despite its importance, this process remains challenging because of the poor correlation between the presence of introduced exogenous DNA and its transcription. Consequently, many transfected cells must be screened to identify those with an appropriate level of expression. To improve the screening process, we investigated the utility of the human interleukin 12 (IL-12) p40 cDNA as a reporter gene for studies of mammalian gene expression and for high-throughput screening of engineered mouse embryonic stem cells. RESULTS: A series of expression plasmids were used to study the utility of IL-12 p40 as an accurate reporter of gene activity. These studies included a characterization of the IL-12 p40 expression system in terms of: (i) a time course of IL-12 p40 accumulation in the medium of transfected cells; (ii) the dose-response relationship between the input DNA and IL-12 p40 mRNA levels and IL-12 p40 protein secretion; (iii) the utility of IL-12 p40 as a reporter gene for analyzing the activity of cis-acting genetic elements; (iv) expression of the IL-12 p40 reporter protein driven by an IRES element in a bicistronic mRNA; (v) utility of IL-12 p40 as a reporter gene in a high-throughput screening strategy to identify successful transformed mouse embryonic stem cells; (vi) demonstration of pluripotency of IL-12 p40 expressing ES cells in vitro and in vivo; and (vii) germline transmission of the IL-12 p40 reporter gene. CONCLUSION: IL-12 p40 showed several advantages as a reporter gene in terms of sensitivity and ease of the detection procedure. The IL-12 p40 assay was rapid and simple, in as much as the reporter protein secreted from the transfected cells was accurately measured by ELISA using a small aliquot of the culture medium. Remarkably, expression of Il-12 p40 does not affect the pluripotency of mouse ES cells. To our knowledge, human IL-12 p40 is the first secreted reporter protein suitable for high-throughput screening of mouse ES cells. In comparison to other secreted reporters, such as the widely used alkaline phosphatase (SEAP) reporter, the IL-12 p40 reporter system offers other real advantages.

Nonoperative treatment of unicompartmental arthritis of the knee.

Treatment of the knee with unicompartmental osteoarthritis remains a challenging clinical problem. Despite pharmacologic advances and surgical innovations, the ideal strategy for the patient who has single-compartment degenerative disease can be complicated. The understanding and management of this problem are further confounded by the fact that so much of the data are unreliable. Given these constraints, this article outlines the current alternatives available in nonoperatively managing the symptomatic unicompartmental arthritic knee.

Rupture of the biceps tendon after arthroscopic thermal capsulorrhaphy.

The use of thermal energy in the shoulder to tighten capsular tissues through collagen denaturation is well established. Although reported complication rates are low, the natural history of thermal manipulation to both target and collateral tissue is poorly defined. We report two cases of biceps tendon rupture after arthroscopic capsular shrinkage. Both patients were young, athletic men with normal long head biceps tendons at the time of surgery. Each patient experienced a complete tear of the long head with distal muscle retraction, resulting in a "Popeye" deformity, at 3 months postoperatively. One patient elected further surgery with biceps tenodesis. Both patients have returned to their athletic activities with minimal functional deficits.

Simulated graft recession in endoscopic ACL reconstruction: influence on graft strain.

Eight fresh cadaveric knee specimens underwent arthroscopic-assisted ACL reconstruction to examine the influence of femoral graft recession on graft strain pattern. Length changes between tibial origin and femoral insertion (simulating graft strain or isometry pattern) were measured throughout knee motion (0 degrees-90 degrees) with a simulated ACL construct. Measurements were taken at the "endo" position (replicating the normal endoscopic position) and in progressive 1.5-mm increments proximally within the femoral tunnel (mimicking femoral graft recession). After recession up to a maximum of 15 mm, a block was placed anterior to the "recessed" graft construct (simulating placement of bone graft anterior to the recessed graft) and strain patterns were remeasured. Graft strain patterns were altered with as little as 1.5 mm recession in two of eight specimens. Compared to the "endo" position, all specimens showed a statistically significant decrease in strain by 3 mm of graft recession (P<.001 for 7 of 8, and P=.0138 for 1 of 8). A direct relationship exists between graft placement and ACL strain patterns, with more proximal graft "recession" adversely influencing normal graft strain. Bone graft placement anterior to the recessed graft restores strain patterns to those seen at the normal "endoscopic" position.

Scientific basis of laser energy.

Lasers are intense beams of energy generated through the stimulation of radiation. Their clinical appeal in arthroscopic applications is based on their preferential absorption by water-containing tissues. Laser-tissue interaction includes reflection, scattering, transmission, and absorption. Clinical effects occur through tissue heating by absorption of laser energy. When power density is sufficient to achieve the ablation threshold, vaporization of tissue results with minimal collateral thermal damage. Further developments in the field of laser medicine may provide us with arthroscopic tools of even greater precision and safety.

Rotator cuff tears in the throwing athlete.

Tears of the rotator cuff, both partial, and less commonly, full thickness, are relatively common in the throwing athlete. The rotator cuff is subjected to enormous stresses during repetitive overhead activity. The supraphysiological strains, especially when combined with pathology elsewhere in the kinetic chain, can lead to compromise of the cuff fabric, most commonly on the undersurface where tensile overload occurs. Exacerbation by a tight posterior capsular, anterior instability, and internal impingement render the cuff progressively compromised, with intrinsic shear stresses and undersurface fiber failure. Advances in imaging technology, including contrast magnetic resonance imaging, dynamic ultrasound, and arthroscopic visualization have enhanced our understanding of cuff pathology in this athletic population. Unfortunately, this has not yet translated into how to best approach these athletes to return them to their previous level of activity. Nonoperative management remains the mainstay for most throwers, with arthroscopic debridement an effective surgical option for those with refractory symptoms. Despite technological advances in cuff repair in the general population, comparable outcomes have not been achieved in high-level throwers. Widespread appreciation that securing the cuff operatively will likely end an athletes' throwing career has led to adopting a surgical approach that emphasizes debridement over repair for nearly all partial and full-thickness tears. Whether advances in surgical technique will ultimately permit definitive and lasting repairs that allow overhead throwers to return to their previous level of sports remains unknown at this time.

Clinical update: MR imaging of the shoulder.

Magnetic resonance imaging has become an important diagnostic adjunct in the evaluation of shoulder conditions, and the technology continues to evolve. Direct magnetic resonance arthrography can improve detection of labral and rotator cuff pathology, especially partial thickness tears of the rotator cuff. Special positioning, such as abducted-externally rotated views, improves visualization of the rotator cuff and posterior superior labrum in throwing athletes. Diagnosis-specific sequencing such as fat suppression, spin-echo and proton-density techniques, and higher power magnets (3.0 T) allow for an unprecedented level of soft tissue detail. Clinical expertize is required to differentiate between normal anatomic variants, incidental findings, and true pathology. Although magnetic resonance imaging findings may be diagnostic in some cases, clinical correlation with history and physical examination findings is critical.

Evaluating protocols for embryonic stem cell differentiation into insulin-secreting beta-cells using insulin II-GFP as a specific and noninvasive reporter.

Stable and full differentiation of pluripotent stem cells into functional beta-cells offers the potential to treat type I diabetes with a theoretically inexhaustible source of replacement cells. In addition to the difficulties in directed differentiation, progress toward an optimized and reliable protocol has been hampered by the complication that cultured cells will concentrate insulin from the media, thus making it difficult to tell which, if any, cells are producing insulin. To address this, we utilized a novel murine embryonic stem cell (mESC) research model, in which the green fluorescent protein (GFP) has been inserted within the C-peptide of the mouse insulinII gene (InsulinII-GFP). Using this method, cells producing insulin are easily identified. We then compared four published protocols for differentiating mESCs into beta-cells to evaluate their relative efficiency by assaying intrinsic insulin production. Cells differentiated using each protocol were easily distinguished based on culture conditions and morphology. This comparison is strengthened because all testing is performed within the same laboratory by the same researchers, thereby removing interlaboratory variability in culture, cells, or analysis. Differentiated cells were analyzed and sorted based on GFP fluorescence as compared to wild type cells. Each differentiation protocol increased GFP fluorescence but only modestly. None of these protocols yielded more than 3% of cells capable of insulin biosynthesis indicating the relative inefficiency of all analyzed protocols. Therefore, improved beta-cells differentiation protocols are needed, and these insulin II GFP cells may prove to be an important tool to accelerate this process.

New approaches to diagnosis and arthroscopic management of partial-thickness cuff tears.

Partial-thickness cuff tears (PTCTs) are increasingly recognized as a source of pain and athletic impairment, especially in overhead athletes. 1,2 Improvements in diagnostic imaging have enhanced the ability to detect and quantify partial cuff disease, and arthroscopic advances have led to novel techniques by which partial cuff tears can be repaired. 2-6 Despite increasing recognition and improved understanding of this condition, the natural history, clinical evaluation, and management of partial tears remain elusive. This is because of the disparity between the extent of partial cuff tearing and the wide variability in clinical impairment and the frequent overlay of concomitant labral and subacromial pathology. When should operating on an athlete with a partial cuff tear be considered? What percentage of cuff tear justifies repair rather than debridement? Does this threshold vary according to the athlete or sport? And if the partial tear is repaired, what can be expected in terms of return to activity, particularly in a high-level thrower? The purpose of this manuscript is to provide an overview of partial cuff tears and their evaluation and management.