Analysis of the performance of a new concept for automatic draping of wide reinforcement fabrics with pre-shear: A virtual prototyping study.

The layup process of large composite structures made from dry reinforcement fabrics is considered. One such structure is a wind turbine blade, for which the current draping process is mostly manual. Automating the draping process will, therefore, lower the costs. Based on a literature review, a new concept is synthesized and analyzed using an advanced finite element model with rigid multi-body kinematics and a dedicated material model for the fabric. The material model is calibrated using experimental coupon tests, i.e. the bias-extension test (shear) and Peirce's cantilever test (out-of-plane bending). The concept is analyzed numerically by means of a simple parameter study and draping test cases on a flat mold as well as a general double-curved mold. The simulation results show that the concept is feasible for the draping operation and is thus qualified for the subsequent physical prototyping.

Republication of "A Novel Casting Technique for Tongue-Type Calcaneus Fractures With Soft Tissue Compromise".

Displaced calcaneal fractures encompass a spectrum of fracture patterns, many of which are associated with soft tissue complications. Displaced tongue-type calcaneal fractures often cause pressure on the posterior heel skin, particularly when treatment is delayed. Resultant partial- or full-thickness skin necrosis presents significant challenges to the treating surgeon. In this article, the authors report on a case of full-thickness skin necrosis associated with a displaced tongue-type calcaneus fracture. The authors describe the use of a specialized heel window casting technique, which eliminates posterior heel pressure and greatly facilitates soft tissue surveillance and local wound care. The article also reviews the literature on soft tissue complications associated with displaced calcaneus fractures.

Factors influencing management of bilateral femur fractures: A multicenter retrospective cohort of early versus delayed definitive Fixation.

INTRODUCTION: The purpose of our study was to evaluate the factors that influence the timing of definitive fixation in the management of bilateral femoral shaft fractures and the outcomes for patients with these injuries. METHODS: Patients with bilateral femur fractures treated between 1998 to 2019 at ten level-1 trauma centers were retrospectively reviewed. Patients were grouped into early or delayed fixation, which was defined as definitive fixation of both femurs within or greater than 24 hours from injury, respectively. Statistical analysis included reversed logistic odds regression to predict which variable(s) was most likely to determine timing to definitive fixation. The outcomes included age, sex, high-volume institution, ISS, GCS, admission lactate, and admission base deficit. RESULTS: Three hundred twenty-eight patients were included; 164 patients were included in the early fixation group and 164 patients in the delayed fixation group. Patients managed with delayed fixation had a higher Injury Severity Score (26.8 vs 22.4; p<0.01), higher admission lactate (4.4 and 3.0; p<0.01), and a lower Glasgow Coma Scale (10.7 vs 13; p<0.01). High-volume institution was the most reliable influencer for time to definitive fixation, successfully determining 78.6% of patients, followed by admission lactate, 64.4%. When all variables were evaluated in conjunction, high-volume institution remained the strongest contributor (X2 statistic: institution: 45.6, ISS: 8.83, lactate: 6.77, GCS: 0.94). CONCLUSION: In this study, high-volume institution was the strongest predictor of timing to definitive fixation in patients with bilateral femur fractures. This study demonstrates an opportunity to create a standardized care pathway for patients with these injuries. LEVEL OF EVIDENCE: Level III.

Single-Stage Versus 2-Stage Bilateral Intramedullary Nail Fixation in Patients With Bilateral Femur Fractures: A Multicenter Retrospective Review.

OBJECTIVE: To evaluate rates of complications in patients with bilateral femur fractures treated with intramedullary nailing (IMN) during either 1 single procedure or 2 separate procedures. DESIGN: A multicenter retrospective review of patients sustaining bilateral femur fractures, treated with IMN in single or 2-stage procedure, from 1998 to 2018 was performed at 10 Level-1 trauma centers. SETTING: Ten Level-1 trauma centers. PATIENTS/PARTICIPANTS: Two hundred forty-six patients with bilateral femur fractures. INTERVENTIONS: Intramedullary nailing. MAIN OUTCOME MEASURES: Incidence of complications. RESULTS: A total of 246 patients were included, with 188 single-stage and 58 two-stage patients. Gender, age, injury severity score, abbreviated injury score, secondary injuries, Glasgow coma scale, and proportion of open fractures were similar between both groups. Acute respiratory distress syndrome (ARDS) occurred at higher rates in the 2-stage group (13.8% vs. 5.9%; P value = 0.05). When further adjusted for age, gender, injury severity score, abbreviated injury score, Glasgow coma scale, and admission lactate, the single-stage group had a 78% reduced risk for ARDS. In-hospital mortality was higher in the single-stage cohort (2.7% compared with 0%), although this did not meet statistical significance (P = 0.22). CONCLUSIONS: This is the largest multicenter study to date evaluating the outcomes between single- and 2-stage IMN fixation for bilateral femoral shaft fractures. Single-stage bilateral femur IMN may decrease rates of ARDS in polytrauma patients who are able to undergo simultaneous definitive fixation. However, a future prospective study with standardized protocols in place will be required to discern whether single- versus 2-stage fixation has an effect on mortality and to identify those individuals at risk. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Association of Perioperative Computed Tomography Hounsfield Units and Failure of Femoral Neck Fracture Fixation.

OBJECTIVES: To determine whether Hounsfield units (HUs) measured on perioperative computed tomographic scans are associated with radiographic outcomes and reoperations after femoral neck fracture fixation. DESIGN: Retrospective cohort study. SETTING: Level I trauma center. PATIENTS: One hundred fourteen patients age ≥18 years, who presented to a Level I trauma center, and who underwent surgical fixation of intracapsular femoral neck fracture and had perioperative computed tomographic scans and adequate follow-up. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Screw penetration, femoral neck shortening >5 mm, and revision surgery. RESULTS: A median follow-up was 23 months. An HU measurement of the femoral head was significantly associated with screw penetration and femoral neck shortening but not revision surgery. Patients with middle femoral head HU measurements <146 had 17 times (95% confidence interval: 4.32-78.9, P < 0.001) increased odds of screw penetration. Greater than 5 mm shortening was seen in patients with HUs <212.5 in the low head section by an odds ratio of 7.8 (95% confidence interval: 2.15-33.0, P = 0.014). CONCLUSION: Outcome differences regarding screw penetration and femoral neck shortening related to the HU or densities of femoral head and neck at the time of fracture are significant. These findings can help the clinician with developing a treatment plan for either arthroplasty or fixation of a femoral neck fracture based on objective bone quality measurements rather than relying on an arbitrary age recommendation. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

A Reliable and Reproducible Critical-Sized Segmental Femoral Defect Model in Rats Stabilized with a Custom External Fixator.

Orthopedic research relies heavily on animal models to study mechanisms of bone healing in vivo as well as investigate the new treatment techniques. Critical-sized segmental defects are challenging to treat clinically, and research efforts could benefit from a reliable, ambulatory small animal model of a segmental femoral defect. In this study, we present an optimized surgical protocol for the consistent and reproducible creation of a 5 mm critical diaphyseal defect in a rat femur stabilized with an external fixator. The diaphyseal ostectomy was performed using a custom jig to place 4 Kirschner wires bicortically, which were stabilized with an adapted external fixator device. An oscillating bone saw was used to create the defect. Either a collagen sponge alone or a collagen sponge soaked in rhBMP-2 was implanted into the defect, and the bone healing was monitored over 12 weeks using radiographs. After 12 weeks, rats were sacrificed, and histological analysis was performed on the excised control and treated femurs. Bone defects containing only collagen sponge resulted in non-union, while rhBMP-2 treatment yielded the formation of a periosteal callous and new bone remodeling. Animals recovered well after implantation, and external fixation proved successful in stabilizing the femoral defects over 12 weeks. This streamlined surgical model could be readily applied to study bone healing and test new orthopedic biomaterials and regenerative therapies in vivo.

Spatiotemporally Controlled Myosin Relocalization and Internal Pressure Generate Sibling Cell Size Asymmetry.

Metazoan cells can generate unequal-sized sibling cells during cell division. This form of asymmetric cell division depends on spindle geometry and Myosin distribution, but the underlying mechanics are unclear. Here, we use atomic force microscopy and live cell imaging to elucidate the biophysical forces involved in the establishment of physical asymmetry in Drosophila neural stem cells. We show that initial apical cortical expansion is driven by hydrostatic pressure, peaking shortly after anaphase onset, and enabled by a relief of actomyosin contractile tension on the apical cell cortex. An increase in contractile tension at the cleavage furrow combined with the relocalization of basally located Myosin initiates basal and sustains apical extension. We propose that spatiotemporally controlled actomyosin contractile tension and hydrostatic pressure enable biased cortical expansion to generate sibling cell size asymmetry. However, dynamic cleavage furrow repositioning can compensate for the lack of biased expansion to establish physical asymmetry.

Development of a Classification Scheme for Examining Adverse Events Associated with Medical Devices, Specifically the DaVinci Surgical System as Reported in the FDA MAUDE Database.

OBJECTIVE: To examine the Manufacturer and User Facility Device Experience Database (MAUDE) database to capture adverse events experienced with the Da Vinci Surgical System. In addition, to design a standardized classification system to categorize the complications and machine failures associated with the device. SUMMARY BACKGROUND DATA: Overall, 1,057,000 DaVinci procedures were performed in the United States between 2009 and 2012. Currently, no system exists for classifying and comparing device-related errors and complications with which to evaluate adverse events associated with the Da Vinci Surgical System. METHODS: The MAUDE database was queried for events reports related to the DaVinci Surgical System between the years 2009 and 2012. A classification system was developed and tested among 14 robotic surgeons to associate a level of severity with each event and its relationship to the DaVinci Surgical System. Events were then classified according to this system and examined by using Chi-square analysis. RESULTS: Two thousand eight hundred thirty-seven events were identified, of which 34% were obstetrics and gynecology (Ob/Gyn); 19%, urology; 11%, other; and 36%, not specified. Our classification system had moderate agreement with a Kappa score of 0.52. Using our classification system, we identified 75% of the events as mild, 18% as moderate, 4% as severe, and 3% as life threatening or resulting in death. Seventy-seven percent were classified as definitely related to the device, 15% as possibly related, and 8% as not related. Urology procedures compared with Ob/Gyn were associated with more severe events (38% vs 26%, p < 0.0001). Energy instruments were associated with less severe events compared with the surgical system (8% vs 87%, p < 0.0001). Events that were definitely associated with the device tended to be less severe (81% vs 19%, p < 0.0001). CONCLUSIONS: Our classification system is a valid tool with moderate inter-rater agreement that can be used to better understand device-related adverse events. The majority of robotic related events were mild but associated with the device.

Detecting Beer Intake by Unique Metabolite Patterns.

Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

Patient pools and the use of "patient means" are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay.

BACKGROUND: Quality control (QC) is an essential part of clinical biochemistry to ensure that laboratory test results are reliable and correct. Those tests without a defined reference method constitute a special challenge, as is the case with bone-specific alkaline phosphatase (BAP). METHODS AND RESULTS: The present study reports an example where a shift in a BAP assay was detected by use of a patient pool and supported by a retrospective calculation of "patient mean", while the external QC and specific assay control material were unaffected by the shift. CONCLUSIONS: Patient pools and the use of patient means remain a useful and inexpensive procedure for internal QC.

Sick in the head? Pathogen concerns bias implicit perceptions of mental illness.

Biases against the mentally ill are historically and cross-culturally pervasive, suggesting they may have an evolutionary basis. The prevailing view is that people seek to distance themselves from the mentally ill because they are perceived as dangerous, violent, and incompetent. However, because of similarities between sickness behaviors and symptoms of some mental disorders, it was hypothesized that mental illness stigma could be partially explained as a function of behavioral immune system biases designed to avoid potential sources of contagion. In two experiments, it was found that mental illness was implicitly associated more with disease than danger. In Experiment 1, this implicit association was exacerbated among people who have had their biological immune system activated by a recent illness. In Experiment 2, experimentally priming disease salience increased implicit association between mental illness and disease. Implications for the evolutionary origins of prejudice and the prevention of mental illness stigma are discussed.

Diabetes mortality differs between registers due to various disease definitions.

INTRODUCTION: We evaluated the impact of including haemolobbing A1c (HbA1c) measurements in a regional algorithm for identification of diabetics by comparing the population identified by the regional algorithm with diabetics registered in the National Danish Diabetes Register (NDR) relative to prevalence, co-morbidity and five-year mortality rate. MATERIAL AND METHODS: The regional (County of Vejle) and national diabetes populations were compared per the inclusion date of 31 December 2006 limited to persons residing in four municipalities in the County of Vejle, Denmark. RESULTS: A total of 14,998 diabetics were identified by the regional algorithm, of whom 11,499 (prevalence 4.1%) resided in the four municipalities. The total number of diabetics registered in the NDR was 227,621 in Denmark, of whom 10,976 (prevalence 4.0%) resided in the four municipalities. The regional diabetics (2,802 persons) not identified in the NDR population had a significantly lower mortality rate (57%) than the diabetics (2,279 persons) in the NDR population not identified by the regional algorithm. CONCLUSION: The significantly higher mortality in the NDR population not identified by the regional algorithm may stem from differences between the components of the two algorithms, i.e. frequency of glucose measurements in the NDR versus frequency of HbA1c measurements including elevated values in the regional algorithm. The NDR algorithm, which includes the use of frequency of glucose measurements without a value over the diagnostic threshold, identified about 21% of persons who probably had their glucose measured for other reasons than diabetes. FUNDING: The Danish Council for Research and Innovation, Region of Southern Denmark's PhD Fund, University of Southern Denmark and the Research Fund, Vejle Hospital. TRIAL REGISTRATION: not relevant.

Predicting brain metastases of breast cancer based on serum S100B and serum HER2.

Brain metastases are a major cause of morbidity and mortality in breast cancer. The aim of the current study was to evaluate the prediction of brain metastases based on serum S100B and human epidermal growth factor receptor 2 (HER2). A total of 107 breast cancer patients were included in the current study from two prospective cohort studies with either elevated serum HER2 levels >15 ng/ml or brain metastases verified by magnetic resonance imaging (MRI) or computer tomography (CT). Following the exclusion of six patients, the remaining 101 patients were divided into two groups: Group 0 (n=55), patients with normal MRI results; and group 1 (n=46), patients with brain metastases. The levels of serum S100B and HER2 in the two groups were analyzed prior to MRI or CT of the brain, and no significant differences were identified in the serum HER2 (P=0.060) or S100B levels (P=0.623) between the groups. The univariate analysis of prognostic factors for brain metastases showed a significant correlation with systemic disease (P<0.001), axillary lymph node metastases (P=0.001) and serum HER2 >30 ng/ml (P=0.002). Only systemic disease (P<0.001) remained statistically significant in the multivariate analysis. In conclusion, serum levels of S100B and HER2 did not predict the risk of brain metastases. In the multivariate analysis, brain metastases were only found to correlate with systemic disease. However, in the univariate analysis, serum HER2 levels >30 ng/ml were identified to correlate with increased risk of brain metastases, which calls for further investigation.

Intermediate-term outcomes after renal cryoablation: results of a multi-institutional study.

PURPOSE: To present intermediate-term oncologic efficacy of cryoablation (CA) for the treatment of patients with small renal masses in a multi-institution multisurgeon cohort. PATIENTS AND METHODS: We retrospectively reviewed billing records and tumor registries, identifying 116 renal tumors in 116 patients treated with CA by six surgeons at four institutions. Patient age, sex, tumor size, RENAL nephrometry score, complications, and recurrences were recorded. RESULTS: One hundred-sixteen patients (66.4% male, 33.6% female) with 116 tumors underwent renal mass CA with a mean follow-up of 27.4 months (range 1-112 mos). Mean tumor size was 2.76 ± 0.97 cm (range 1.1-5.5 cm). Twenty-seven complications occurred in 23 patients for an overall complication rate of 19.8%. Low-grade complications (Clavien I and II) accounted for 92.6% (n=25) of overall complications. Seven (6%) patients had enhancement on initial imaging and were considered incomplete ablations. Local recurrence and metastatic disease developed in four and one patients, respectively. In patients with biopsy-proven renal-cell carcinoma (RCC), the 2- and 5-year recurrence-free survival (RFS) probability was 0.83 (95% confidence interval [CI]: 0.74, 0.95) and 0.77 (95% CI: 0.60, 0.94), respectively. After excluding biopsy proven RCC patients with incomplete ablations, the 2- and 5-year RFS increased to 0.91 (95% CI: 0.82, 1.00) and 0.85 (95% CI: 0.71, 1.00) respectively. CONCLUSION: CA of renal masses results in acceptable oncologic efficacy accompanied by a tolerable complication profile in a cohort with a mean follow-up of 27.4 months. CA remains a viable treatment option for small renal masses in selected patients.

A role for MEIS1 in MLL-fusion gene leukemia.

Leukemias with MLL rearrangements are characterized by high expression of the homeobox gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplantation recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA-mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell-cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor.

Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells.

The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin(-)Sca1(+)c-kit(+)) stem cells, while committed granulocyte-monocyte progenitors (GMPs) were transformation resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll-AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 upregulated expression of 192 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.

Fluorogenic substrates for high-throughput measurements of endothelial lipase activity.

Endothelial lipase (EL) has been shown to be a critical determinant for high density lipoprotein cholesterol levels in vivo; therefore, assays that measure EL activity have become important for the discovery of small molecule inhibitors that specifically target EL. Here, we describe fluorescent Bodipy-labeled substrates that can be used in homogeneous, ultra-high-throughput kinetic assays that measure EL phospholipase or triglyceride lipase activities. Triton X-100 detergent micelles and synthetic HDL particles containing Bodipy-labeled phospholipid or Bodipy-labeled triglyceride substrates were shown to be catalytic substrates for EL, LPL, and HL. More importantly, only synthetic HDL particles containing Bodipy-labeled triglyceride were ideal substrates for EL, LPL, and HL in the presence of high concentrations of human or mouse serum. These data suggest that substrate presentation is a critical factor when determining EL activity in the presence of serum.

Different roles of liver X receptor alpha and beta in lipid metabolism: effects of an alpha-selective and a dual agonist in mice deficient in each subtype.

Liver X receptor (LXR) alpha and LXRbeta are closely related nuclear receptors that respond to elevated levels of intracellular cholesterol by enhancing transcription of genes that control cholesterol efflux and fatty acid biosynthesis. The consequences of inactivation of either LXR isoform have been thoroughly studied, as have the effects of simultaneous activation of both LXRalpha and LXRbeta by synthetic compounds. We here describe the effects of selective activation of LXRalpha or LXRbeta on lipid metabolism. This was accomplished by treating mice genetically deficient in either LXRalpha or LXRbeta with an agonist with equal potency for both isoforms (Compound B) or a synthetic agonist selective for LXRalpha (Compound A). We also determined the effect of these agonists on gene expression and cholesterol efflux in peritoneal macrophages derived from wild-type and knockout mice. Both compounds raised HDL-cholesterol and increased liver triglycerides in wild-type mice; in contrast, in mice deficient in LXRalpha, Compound B increased HDL-cholesterol but did not cause hepatic steatosis. Compound B induced ATP-binding cassette transporter (ABC) A1 expression and stimulated cholesterol efflux in macrophages from both LXRalpha and LXRbeta-deficient mice. Our data lend further experimental support to the hypothesis that LXRbeta-selective agonists may raise HDL-cholesterol and stimulate macrophage cholesterol efflux without causing liver triglyceride accumulation.

EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 3 - 2005.

The EC4 Syllabus for Postgraduate Training is the basis for the European Register of Specialists in Clinical Chemistry and Laboratory Medicine. The syllabus: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. The syllabus is not primarily meant to be a training guide, but on the basis of the overview given (common minimal programme), national societies should formulate programmes that indicate where knowledge and experience is needed. The main points of this programme are: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. The aim of this version of the syllabus is to be in accordance with the Directive of Professional Qualifications published on 30 September 2005. To prepare the common platforms planned in this directive, the disciplines are divided into four categories: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. General chemistry, encompassing biochemistry, endocrinology, chemical (humoral), immunology, toxicology, and therapeutic drug monitoring; Haematology, covering cells, transfusion serology, coagulation, and cellular immunology; Microbiology, involving bacteriology, virology, parasitology, and mycology; Genetics and IVF.