What is the abdomen? Rationalising clinical and anatomical perspectives using formal semantics.

The meaning of the term 'abdomen' has become increasingly ambiguous, as it has to satisfy the contemporary requirements of natural language discourse, literature, gross and radiological anatomy and its role in ontologies supporting electronic records and data modelling. It is critical that there is an agreed understanding of the semantics of the abdominopelvic cavity, its component volumes including the abdomen proper, true and false pelvic cavities, and its boundaries and regional contents. The expression of part-whole (meronymic) relationships is essential for inferences to be drawn by computer algorithms, but unless these are rigorously reviewed and tested incorrect assumptions are drawn. The SNOMED CT terminology descriptions and hierarchy of anatomical concepts relating to the trunk were scrutinised for ambiguity and sub-optimal relationships using a panel of reference sources. Any identified errors were corrected and the impact of any changes reviewed iteratively by evaluating their effect on dependant hierarchies (modelled with the associated anatomical concepts). Anatomical concepts are generally structured according to a traditional gross standpoint, but in clinical practice covert complex regional notions are frequently used and during the evaluation process a new viewpoint relating to projectional (transmissive) or emissive radiological perspective was identified. The subtle but important differences in the boundaries, volumes and contents of these distinctive perspectives of the 'abdomen' are presented. Three significant complex variants have been identified which relate to the most common uses of the word 'abdomen'. The merits and disadvantages of using 'abdomen' as common synonym to more than one concept (polysemy) are briefly discussed and the solution adopted by SNOMED International described. The review of existing ontologies and academic literature confirmed the frequent varied use of the word 'abdomen', which raises concerns when derived data are increasingly being used remotely from the point of clinical contact, potentially leading to incorrect inferences. The documented regional truncal volumes from an anatomical regional, segmental and cross-sectional perspective have been integrated into a logical and comprehensive model suitable for computer processing. The robust modelling of meronymic hierarchies has to be rigorous to avoid systematic errors and it is thus timely that a proposed standard description of these subtly related volumes and structures is made available for discussion and comment.

Utilizing 3D-Printed Orbital Floor Stamps to Create Patient-Specific Implants for Orbital Floor Reconstruction.

PURPOSE: This study seeks to test a novel technique of custom-printed midface contour models with orbital floor "stamps" to guide reconstruction of orbital floor blowout fractures, with or without concomitant zygomaticomaxillary complex injury. METHODS: A series of 4 consecutive patients with orbital floor blowout fractures (including 3 with zygomatic maxillary complex fractures) were retrospectively examined for outcomes associated with orbital floor reconstruction using 3-dimensional-printed stamps and midface models. Data collected included demographics, pre- and postoperative visual globe malposition, motility, and visual field disturbances. Three-dimensional printing methodology is reported, as well as associated costs and time required to generate the models and stamps. RESULTS: The cost of producing a midface-contour model and orbital floor stamps was $131, inclusive of labor and materials. Cases averaged 170 minutes to segment, design, and print. Patients with preoperative diplopia and motility restrictions had resolution of their symptoms. Two patients had resolution of their enophthalmos, while one patient with a concomitant zygomaticomaxillary fracture had persistent mild enophthalmos. CONCLUSIONS: Midface contour models and orbital floor stamps may be produced in a timely and cost-effective manner. Use of these "homemade" stamps allows for patient-specific custom-contoured orbital floor reconstruction. Further studies are warranted to examine long-term visual and esthetic outcomes for these patients.

Attainment of Water and Oil Repellency for Engineering Thermoplastics without Long-Chain Perfluoroalkyls: Perfluoropolyether-Based Triblock Polyester Additives.

For decades, water and oil repellency of engineering thermoplastics has been achieved with introduction of long-chain perfluoroalkyl substances and moieties (C nF2 n+1, n ≥ 7). However, their bioaccumulative and toxicological impact is now widely recognized and, consequently, the substances have been phased out of industrial production and applications. To this end, we have synthesized fluorinated oligomeric triblock polyesters (FOPBs), which do not possess the long-chain perfluoroalkyl segments and serve as effective low-surface-energy additives to engineering thermoplastics. More specifically, we obtained original perfluoropolyether (PFPE)-based triblock copolymers, in which two identical fluorinated blocks were separated by a short nonfluorinated polyester block made of poly(ethylene isophthalate) (PEI). It was found that when FOPBs were added to poly(ethylene terephthalate), nylon-6, and poly(methyl methacrylate) films they readily migrate to the film surface and in doing so imparted significant water and oil repellency to the thermoplastic boundary. The water/oil wettability of the films modified with FOPB is considerably lower than the wettability of the films modified with an analogous PFPE-based polyester, which differs from FOPB only by the absence of the short nonfluorinated PEI middle block. We associate the superiority of the triblock copolymers in terms of water and oil repellency with their ability to form brushlike structures on polymer film surfaces.

Development and Validation of a Brain Phantom for Therapeutic Cooling Devices.

Tissue cooling has been proven as a viable therapy for multiple conditions and injuries and has been applied to the brain to treat epilepsy and concussions, leading to improved long-term outcomes. To facilitate the study of temperature reduction as a function of various cooling methods, a thermal brain phantom was developed and analyzed. The phantom is composed of a potassium-neutralized, superabsorbent copolymer hydrogel. The phantom was tested in a series of cooling trials using a cooling block and 37 deg water representing nondirectional blood flow ranging up to 6 gph, a physiologically representative range based on the prototype volume. Results were compared against a validated finite difference (FD) model. Two sets of parameters were used in the FD model: one set to represent the phantom itself and a second set to represent brain parenchyma. The model was then used to calculate steady-state cooling at a depth of 5 mm for all flow rates, for both the phantom and a model of the brain. This effort was undertaken to (1) validate the FD model against the phantom results and (2) evaluate how similar the thermal response of the phantom is to that of a perfused brain. The FD phantom model showed good agreement with the empirical phantom results. Furthermore, the empirical phantom agreed with the predicted brain response within 3.5% at physiological flow, suggesting a biofidelic thermal response. The phantom will be used as a platform for future studies of thermally mediated therapies applied to the cerebral cortex.

N-terminally truncated FOXP1 protein expression and alternate internal FOXP1 promoter usage in normal and malignant B cells.

Strong FOXP1 protein expression is a poor risk factor in diffuse large B-cell lymphoma and has been linked to an activated B-cell-like subtype, which preferentially expresses short FOXP1 (FOXP1S) proteins. However, both short isoform generation and function are incompletely understood. Here we prove by mass spectrometry and N-terminal antibody staining that FOXP1S proteins in activated B-cell-like diffuse large B-cell lymphoma are N-terminally truncated. Furthermore, a rare strongly FOXP1-expressing population of normal germinal center B cells lacking the N-terminus of the regular long protein (FOXP1L) was identified. Exon-targeted silencing and transcript analyses identified three alternate 5' non-coding exons [FOXP1-Ex6b(s), FOXP1-Ex7b and FOXP1-Ex7c], downstream of at least two predicted promoters, giving rise to FOXP1S proteins. These were differentially controlled by B-cell activation and methylation, conserved in murine lymphoma cells, and significantly correlated with FOXP1S protein expression in primary diffuse large B-cell lymphoma samples. Alternatively spliced isoforms lacking exon 9 (e.g. isoform 3) did not encode FOXP1S, and an alternate long human FOXP1 protein (FOXP1AL) likely generated from a FOXP1-Ex6b(L) transcript was detected. The ratio of FOXP1L:FOXP1S isoforms correlated with differential expression of plasmacytic differentiation markers in U-2932 subpopulations, and altering this ratio was sufficient to modulate CD19 expression in diffuse large B-cell lymphoma cell lines. Thus, the activity of multiple alternate FOXP1 promoters to produce multiple protein isoforms is likely to regulate B-cell maturation.

Multiple Small Diameter Drillings Increase Femoral Neck Stability Compared with Single Large Diameter Femoral Head Core Decompression Technique for Avascular Necrosis of the Femoral Head.

Femoral head core decompression is an efficacious joint-preserving procedure for treatment of early stage avascular necrosis. However, postoperative fractures have been described which may be related to the decompression technique used. Femoral head decompressions were performed on 12 matched human cadaveric femora comparing large 8mm single bore versus multiple 3mm small drilling techniques. Ultimate failure strength of the femora was tested using a servo-hydraulic material testing system. Ultimate load to failure was compared between the different decompression techniques using two paired ANCOVA linear regression models. Prior to biomechanical testing and after the intervention, volumetric bone mineral density was determined using quantitative computed tomography to account for variation between cadaveric samples and to assess the amount of bone disruption by the core decompression. Core decompression, using the small diameter bore and multiple drilling technique, withstood significantly greater load prior to failure compared with the single large bore technique after adjustment for bone mineral density (p< 0.05). The 8mm single bore technique removed a significantly larger volume of bone compared to the 3mm multiple drilling technique (p< 0.001). However, total fracture energy was similar between the two core decompression techniques. When considering core decompression for the treatment of early stage avascular necrosis, the multiple small bore technique removed less bone volume, thereby potentially leading to higher load to failure.

Fibrin glue augmentation for flexor tendon repair increases friction compared with epitendinous suture.

PURPOSE: To compare the gliding resistance, repair gapping, and ultimate strength of a common suture construct with a modified construct with fibrin glue augmentation. METHODS: Twelve human cadaveric flexor digitorum profundus tendons were transected and repaired with a 4-strand core suture. Specimens were divided into 2 groups and augmented with epitendinous suture (n = 6) or fibrin glue (n = 6). We compared gliding resistance, 2-mm gapping, and ultimate strength of the repaired tendon between groups. RESULTS: The linear stiffness, force to produce a 2-mm gap, and ultimate failure were similar in both repair methods. However, the 4-strand suture repair with fibrin glue augmentation displayed significantly higher gliding resistance compared with the 4-strand suture with a running epitendinous suture. CONCLUSIONS: The significantly increased gliding resistance associated with fibrin glue raises questions regarding the use of this material for flexor tendon repair augmentation. CLINICAL RELEVANCE: In a human cadaveric study, fibrin glue augmentation to zone II flexor tendon repairs significantly increased friction in the tendon sheath compared with an epitendinous suture.

Robust classification of functional and quantitative image data using functional mixed models.

This article introduces new methods for performing classification of complex, high-dimensional functional data using the functional mixed model (FMM) framework. The FMM relates a functional response to a set of predictors through functional fixed and random effects, which allows it to account for various factors and between-function correlations. The methods include training and prediction steps. In the training steps we train the FMM model by treating class designation as one of the fixed effects, and in the prediction steps we classify the new objects using posterior predictive probabilities of class. Through a Bayesian scheme, we are able to adjust for factors affecting both the functions and the class designations. While the methods can be used in any FMM framework, we provide details for two specific Bayesian approaches: the Gaussian, wavelet-based FMM (G-WFMM) and the robust, wavelet-based FMM (R-WFMM). Both methods perform modeling in the wavelet space, which yields parsimonious representations for the functions, and can naturally adapt to local features and complex nonstationarities in the functions. The R-WFMM allows potentially heavier tails for features of the functions indexed by particular wavelet coefficients, leading to a down-weighting of outliers that makes the method robust to outlying functions or regions of functions. The models are applied to a pancreatic cancer mass spectroscopy data set and compared with other recently developed functional classification methods.

Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia.

Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in 'Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315-1325, 1998; Sheen et al. in 'Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69-76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in 'MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789-801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (alpha-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventricular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell adhesion and loss of neuroependymal integrity.

Towards a Long-Chain Perfluoroalkyl Replacement: Water and Oil Repellent Perfluoropolyether-Based Polyurethane Oligomers.

Original perfluoropolyether (PFPE)-based oligomeric polyurethanes (FOPUs) with different macromolecular architecture were synthesized (in one step) as low-surface-energy materials. It is demonstrated that the oligomers, especially the ones terminated with CF3 moieties, can be employed as safer replacements to long-chain perfluoroalkyl substances/additives. The FOPU macromolecules, when added to an engineering thermoplastic (polyethylene terephthalate, PET) film, readily migrate to the film surface and bring significant water and oil repellency to the thermoplastic boundary. The best performing FOPU/PET films have reached the level of oil wettability and surface energy significantly lower than that of polytetrafluoroethylene, a fully perfluorinated polymer. Specifically, the highest level of the repellency is observed with an oligomeric additive, which was made using aromatic diisocyanate as a comonomer and has CF3 end-group. This semicrystalline oligomer has a glass transition temperature (Tg) well above room temperature, and we associate the superiority of the material in achieving low water and oil wettability with its ability to effectively retain CF3 and CF2 moieties in contact with the test wetting liquids.

Deployment and testing of an automated medical equipment service communication and documentation system at a rural hospital in Kenya.

BACKGROUND: The Medical Equipment Network Documentation System (MENDS) provides a simple communication network for equipment servicing from failure to restoration. It is a text messaging-based platform, designed to use existing technologies in place in low- and middle-income settings. The system gathers and relays information about equipment service requests and reports and automatically saves them to an online database. METHODS: MENDS was deployed at a high volume, rural, charity medical facility in Kijabe, Kenya for a 3-mo pilot test. RESULTS: The results show MENDS more than tripled documentation and enhanced ease and speed of communication. CONCLUSIONS: Comprehensive data provided by MENDS created more accurate measures of equipment performance, which can be used to decrease the time that equipment is out of service and improve the efficiency of repairs, equipment quality and procurement.

Automated 3D Analysis of Zygomaticomaxillary Fracture Rotation and Displacement.

BACKGROUND: The zygomaticomaxillary complex (ZMC) can experience a multitude of deforming forces. There is limited understanding on which deformities alter patient outcomes. This study utilized an automated, three-dimensional analysis to elucidate which fracture patterns and rotational deformities are most prevalent and associated with postoperative complications. METHODS: This study was a 7-year retrospective review of patients with unilateral ZMC fractures who underwent surgical intervention. Patient demographics, injury mechanisms, presenting symptoms, and postoperative outcomes were collected. Segmentation was completed using Mimics software. The lateral-medial, superior-inferior, and anterior-posterior axes were manually identified on the zygoma and then displacement, rotational direction, and rotational degrees were automatically calculated using Geomagic software. Total displacement score was generated by summation of individual displacement scores at each of the five sutures. RESULTS: Eighty-one patients satisfied inclusion criteria. The most prevalent rotational pattern of the zygoma was medially-superiorly-posteriorly (P < 0.001). When comparing rotation along the three axes, the zygoma had the greatest rotation along the lateral-medial axis compared with the superior-inferior (P = 0.003) and anterior-posterior (P < 0.001) axes. Within each axis, the zygoma was more likely to rotate medially than laterally (P = 0.003) and posteriorly than anteriorly (P = 0.01). Multivariate analysis identified total displacement scores and degrees rotated along the lateral-medial axis as significant predictors of facial complications and reoperation. CONCLUSIONS: This study suggests that patients with unilateral ZMC fractures who undergo surgical intervention are at an increased risk for adverse outcomes with greater rotation along the lateral-medial axis and higher total displacement scores. Additionally, the automated analysis method described can provide objective data to better characterize ZMC fractures.

Aberrant expression of the neuronal transcription factor FOXP2 in neoplastic plasma cells.

FOXP2 mutation causes a severe inherited speech and language defect, while the related transcription factors FOXP1, FOXP3 and FOXP4 are implicated in cancer. FOXP2 mRNA and protein expression were characterised in normal human tissues, haematological cell lines and multiple myeloma (MM) patients' samples. FOXP2 mRNA and protein were absent in mononuclear cells from different anatomical sites, lineages and stages of differentiation. However, FOXP2 mRNA and protein was detected in several lymphoma (8/20) and all MM-derived cell lines (n = 4). FOXP2 mRNA was expressed in bone marrow samples from 96% of MM patients (24/25), 66.7% of patients with the pre-neoplastic plasma cell proliferation monoclonal gammopathy of undetermined significance (MGUS) (6/9), but not in reactive plasma cells. The frequency of FOXP2 protein expression in CD138(+) plasma cells was significantly higher in MGUS (P = 0.0005; mean 46.4%) and MM patients (P < or = 0.0001; mean 57.3%) than in reactive marrows (mean 2.5%). FOXP2 (>10% nuclear positivity) was detectable in 90.2% of MM (55/61) and 90.9% of MGUS (10/11) patients, showing more frequent expression than CD56 and labelling 75% of CD56-negative MM (9/12). FOXP2 represents the first transcription factor whose expression consistently differentiates normal and abnormal plasma cells and FOXP2 target genes are implicated in MM pathogenesis.

Ribosome-associated nucleophosmin 1: increased expression and shuttling activity distinguishes prognostic subtypes in chronic lymphocytic leukaemia.

Two distinct groups of chronic lymphocytic leukaemia (CLL) are distinguished by the presence or absence of somatic hypermutation of the immunoglobulin heavy-chain gene. CLL without somatic hypermutation has an adverse outcome, but the precise biological differences that underlie this more aggressive clinical-course are unclear. Using a proteomic approach, we found that the two prognostic forms of CLL were consistently distinguished according to their protein expression pattern. The most important difference observed related to the different expression of nucleophosmin 1 between the two forms of CLL. This different expression was not related to apoptosis, proliferation or gene mutation. However, co-immunoprecipitation experiments identified an association between nucleophosmin 1 and ribosomal proteins. Using immunocytofluorescence, nucleophosmin 1 expression was identified in the nucleoli and nucleoplasm of all cells, but in a proportion of cells, nucleophosmin had been transferred from the nucleoplasm to the cytoplasm. Both the fluorescent intensity, and the frequency of cytoplasmic nucleophosmin 1 expression, was higher in CLL without somatic hypermutation. We propose therefore, that nucleophosmin 1, in association with ribosomal proteins, undergoes nucleo-cytoplasmic shuttling in CLL. This process is most prominent in un-mutated CLL and may signify altered protein biosynthesis.

The complete family of epidermal growth factor receptors and their ligands are co-ordinately expressed in breast cancer.

The levels of expression of the four receptors and eleven ligands composing the epidermal growth factor family were measured using immunohistochemical staining in one hundred cases of breast cancer. All of the family were expressed to some degree in some cases; however, individual cases showed a very wide range of expression of the family from essentially none to all the factors at high levels. The highest aggregate level of expression of a receptor was HER2 followed by HER1, then HER3, then HER4. The ligands (including two splice variants of the NRG1 and NRG2 genes) broadly fell into three groups, those with the highest aggregate expression were Epigen, Epiregulin, Neuregulin 1alpha, Neuregulin 2alpha, Neuregulin 2beta, Neuregulin 4 and TGFalpha, moderate expression was seen with EGF, Neuregulin 1beta and Neuregulin 3, and relatively low levels of expression were seen of HB-EGF, Betacellulin and Amphiregulin. Statistical analysis using Spearman's Rank Correlation showed a positive correlation of expression between each of the factors. Analysing the data using the Cox Proportional Hazards model showed that, in this dataset, the most powerful predictors of relapse free interval and overall survival were the combined measurement of only Epigen and Neuregulin 4.

Effect of jet stretch and particle load on cellulose nanocrystal-alginate nanocomposite fibers.

Alginate fibers have found many applications such as the preparation of dressings to treat exuding wounds, drug delivery, enzyme immobilization, etc.; however, their use is limited due to poor mechanical properties. Cellulose nanocrystals (CNCs) were isolated from cotton and introduced into calcium alginate fibers with the goal of improving their strength and modulus. The isolated CNCs are elongated nanoparticles of crystalline cellulose with an average length of 130 nm with a standard deviation (s) of 63 nm, an average width of 20.4 nm (s = 7.8 nm), and an average height of 6.8 nm (s = 3.3 nm). The CNCs were mixed with an aqueous sodium alginate dope solution and wet spun into a CaCl(2) bath to form fibers. It was found that if the apparent jet stretch (ratio of the fiber draw velocity to extrusion velocity) is kept constant, addition of the nanocrystals reduces the tensile strength and modulus of the material; however, a small concentration of CNCs in the dope solution increases the tensile energy to break and enables an increase in the fiber spinning apparent jet stretch ratio by nearly 2-fold at up to 25% CNCs load; the maximum ratio of 4.6 is observed at 25 wt % CNC loading as compared to a maximum of 2.4 for the native alginate. Mechanical testing showed a 38% increase in tenacity and a 123% increase in tensile modulus with 10 wt % CNCs loading and an apparent jet stretch of 4.2. The data suggest that alignment of the nanocrystals in the composites is a key factor influencing the mechanical properties. CNCs have potential to become a biocompatible, renewable, and cost-effective solution to reinforce alginate fibers.

Cost Analysis for In-house versus Industry-printed Skull Models for Acute Midfacial Fractures.

Industry-printed (IP) 3-dimensional (3D) models are commonly used for secondary midfacial reconstructive cases but not for acute cases due to their high cost and long turnaround time. We have begun using in-house (IH) printed models for complex unilateral midface trauma. We hypothesized that IH models would decrease cost and turnaround time, compared with IP models. METHODS: We retrospectively examined cost and turnaround time data from midface trauma cases performed in 2017-2019 using 3D models (total, n = 15; IH, n = 10; IP, n = 5). Data for IH models were obtained through itemized cost reports from our Biomedical Engineering Department, where the models were printed. Data associated with IP models were obtained through itemized cost reports from our industry vendor. Perioperative data were collected from electronic medical records. RESULTS: The average cost for IH models ($236.38 ± 26.17) was significantly less (P < 0.001) than that for IP models ($1677.82 ± 488.43). Minimal possible time from planning to model delivery was determined. IH models could be produced in as little as 4.65 hours, whereas the IP models required a minimum of 5 days (120 hours) from order placement. There were no significant differences in average operating room time (P = 0.34), surgical complications, or subjective outcomes, but there was a significant difference in estimated blood loss (P = 0.04). CONCLUSION: Utilization of IH 3D skull models is a creative and practical adjunct to complex unilateral midfacial trauma that also reduces cost and turnaround time compared with IP 3D models.

Development and Multi-Scale Validation of a Finite Element Football Helmet Model.

Head injury is a growing concern within contact sports, including American football. Computational tools such as finite element (FE) models provide an avenue for researchers to study, and potentially optimize safety tools, such as helmets. The goal of this study was to develop an accurate representative helmet model that could be used in further study of head injury to mitigate the toll of concussions in contact sports. An FE model of a Schutt Air XP Pro football helmet was developed through three major steps: geometry development, material characterization, and model validation. The fully assembled helmet model was fit onto a Hybrid III dummy head-neck model and National Operating Committee on Standards for Athletic Equipment (NOCSAE) head model and validated through a series of 67 representative impacts similar to those experienced by a football player. The kinematic and kinetic response of the model was compared to the response of the physical experiments, which included force, head linear acceleration, head angular velocity, and carriage acceleration. The outputs between the model and the physical tests were quantitatively evaluated using CORelation and Analysis (CORA), amounting to an overall averaged score of 0.76. The model described in this study has been extensively validated and can function as a building block for innovation in player safety.

Correction to: Development and Multi-Scale Validation of a Finite Element Football Helmet Model.

This correction is to add the middle initials of all authors, which were inadvertently omitted from the original article.