Full-field bulge test for planar anisotropic tissues: Part II – A thin shell method for determining material parameters and comparison of two distributed fiber modeling approaches

A thin shell method is presented to analyze the results of the bulge test presented in Part I of this paper. The method accounts for the effects of bending, which can be significant for thick tissues inflated from a planar state. We fit two commonly used hyperelastic distributed fiber constitutive models to the stretch–stress resultant data for human skin tissue calculated in Part I from the measured inflation pressure and deformed geometry of the tissue. To validate the method, the resulting parameters were implemented in a specimen-specific finite-element analysis. The method was capable of reproducing the experimentally measured pressure–stretch response of the tissue for a fully integrated distributed fiber model, but not for the pre-integrated distributed fiber models. The parameters obtained for the pre-integrated models significantly underestimated the anisotropic properties of the tissue. The thin shell method presented in this work has been applied to human skin tissues but is sufficiently general to be applied to analyze the inflation response of other planar tissues.     

Validity of using tri-axial accelerometers to measure human movement—Part I: Posture and movement detection

A robust method for identifying movement in the free-living environment is needed to objectively measure physical activity. The purpose of this study was to validate the identification of postural orientation and movement from acceleration data against visual inspection from video recordings. Using tri-axial accelerometers placed on the waist and thigh, static orientations of standing, sitting, and lying down, as well as dynamic movements of walking, jogging and transitions between postures were identified. Additionally, subjects walked and jogged at self-selected slow, comfortable, and fast speeds. Identification of tasks was performed using a combination of the signal magnitude area, continuous wavelet transforms and accelerometer orientations. Twelve healthy adults were studied in the laboratory, with two investigators identifying tasks during each second of video observation. The intraclass correlation coefficients for inter-rater reliability were greater than 0.95 for all activities except for transitions. Results demonstrated high validity, with sensitivity and positive predictive values of greater than 85% for sitting and lying, with walking and jogging identified at greater than 90%. The greatest disagreement in identification accuracy between the algorithm and video occurred when subjects were asked to fidget while standing or sitting. During variable speed tasks, gait was correctly identified for speeds between 0.1 m/s and 4.8 m/s. This study included a range of walking speeds and natural movements such as fidgeting during static postures, demonstrating that accelerometer data can be used to identify orientation and movement among the general population.     

Validity of using tri-axial accelerometers to measure human movement – Part II: Step counts at a wide range of gait velocities

A subject-specific step counting method with a high accuracy level at all walking speeds is needed to assess the functional level of impaired patients. The study aim was to validate step counts and cadence calculations from acceleration data by comparison to video data during dynamic activity. Custom-built activity monitors, each containing one tri-axial accelerometer, were placed on the ankles, thigh, and waist of 11 healthy adults. ICC values were greater than 0.98 for video inter-rater reliability of all step counts. The activity monitoring system (AMS) algorithm demonstrated a median (interquartile range; IQR) agreement of 92% (8%) with visual observations during walking/jogging trials at gait velocities ranging from 0.1 to 4.8 m/s, while FitBits (ankle and waist), and a Nike Fuelband (wrist) demonstrated agreements of 92% (36%), 93% (22%), and 33% (35%), respectively. The algorithm results demonstrated high median (IQR) step detection sensitivity (95% (2%)), positive predictive value (PPV) (99% (1%)), and agreement (97% (3%)) during a laboratory-based simulated free-living protocol. The algorithm also showed high median (IQR) sensitivity, PPV, and agreement identifying walking steps (91% (5%), 98% (4%), and 96% (5%)), jogging steps (97% (6%), 100% (1%), and 95% (6%)), and less than 3% mean error in cadence calculations.     

Novel use of an OSCE to assess medical students’ responses to a request for a low value diagnostic imaging test: A mixed methods analysis

ObjectiveEvaluate medical students’ communication skills with a standardized patient (SP) requesting a low value test and describe challenges students identify in addressing the request.MethodsIn this mixed-methods study, third-year students from two medical schools obtained a history, performed a physical examination, and counseled an SP presenting with uncomplicated low back pain who requests an MRI which is not indicated. SP raters evaluated student communication skills using a 14-item checklist. Post-encounter, students reported whether they ordered an MRI and challenges faced.ResultsStudents who discussed practice guidelines and risks of unnecessary testing with the SP were less likely to order an MRI. Students cited several challenges in responding to the SP request including patient characteristics and circumstances, lack of knowledge about MRI indications and alternatives, and lack of communication skills to address the patient request.ConclusionsMost students did not order an MRI for uncomplicated LBP, but only a small number of students educated the patient about the evidence to avoid unnecessary imaging or the harm of unnecessary testing.Practice implicationsKnowledge about unnecessary imaging in uncomplicated LBP may be insufficient to adhere to best practices and longitudinal training in challenging conversations is needed.     

Effects of inspiratory impedance on hemodynamic responses to a squat–stand test in human volunteers: implications for treatment of orthostatic hypotension

Recent studies in our laboratory demonstrated that spontaneous breathing through an inspiratory impedance threshold device (ITD) increased heart rate (HR), stroke volume (SV), cardiac output (Q), and mean arterial blood pressure (MAP) in supine human subjects. In this study, we tested the effectiveness of an ITD as a countermeasure against development of orthostatic hypotension, provoked using a squat-to-stand test (SST). Using a prospective, randomized blinded protocol, 18 healthy, normotensive volunteers (9 males, 9 females) completed two-counterbalanced 6-min SST protocols with and without (sham) an ITD set to open at 0.7 kPa (7-cm H₂O) pressure. HR, SV, Q, total peripheral resistance (TPR), and MAP were assessed noninvasively with infrared finger photoplethysmography. Symptoms were recorded on a 5-point scale (1=normal; 5=faint) of subject perceived rating (SPR). The reduction in TPR produced by SST (–35±5 %) was not affected by the ITD. Reduction in MAP with ITD during the transient phase of the SST (–3.6±0.5 kPa or –27±4 mmHg) was less (P=0.03) than that measured while breathing through a sham device (–4.8±0.4 kPa or –36±3 mmHg) despite similar (P<0.926) elevations in HR of 15±2 bpm. SV (+2±4 %) and Q (+22±5 %) with the ITD were higher (P<0.04) than SV (–8±4 %) and Q (+10±6 %) without the ITD. SPR was 1.4±0.1 with ITD compared to 2.0±0.2 with the sham device (P<0.04). This reduction in orthostatic symptoms with application of an ITD during the SST was associated with higher MAP, SV and Q. Our results demonstrate the potential application of an ITD as a countermeasure against orthostatic hypotension.     

Type I cytokine profiles of human naïve and memory B lymphocytes: a potential for memory cells to impact polarization

B cells bifurcating along ‘type 1’ or ‘type 2’ pathways under the influence of polarizing cytokines can, in turn, influence the direction of an immune response. Here, we compare the capacity of human B cells residing within naïve and memory compartments to participate in type 1 polarizing responses. B‐cell receptor (BCR) engagement provided the main signal for interleukin (IL)‐12Rβ1 expression in the two subsets: this was potentiated by CD154 together with interferon‐γ (IFN‐γ) but inhibited by IL‐12. IL‐12Rβ2 could be induced on a minority of B cells by the same signals, and also by IFN‐γ alone. WSX‐1, a receptor for IL‐27, was expressed in both subsets with no evidence for its regulation by the signals studied. While neither subset was capable of secreting much IL‐12 p70, memory B cells could produce a small amount of IL‐12 p40 on CD40 ligation. Memory B cells also, exclusively, expressed IL‐23 p19 mRNA on BCR triggering. Importantly, products of appropriately stimulated memory – but not naive – B cells were shown to promote the synthesis of IFN‐γ in uncommitted T‐helper cells. The data indicate an equal capacity for naïve and memory B cells to respond within a type 1 polarizing environment. Although poorly equipped for initiating type 1 responses, B cells – by virtue of the memory subset – reveal a capacity for their maintenance and amplification following T‐dependent signalling.     

Preparation of a collagen/polymer hybrid gel designed for tissue membranes. Part I: Controlling the polymer–collagen cross-linking process using an ethanol/water co-solvent

The drawback with collagen/2-methacryloyloxyethyl phosphorylcholine (MPC) polymer hybrid gels (collagen/phospholipid polymer hybrid gels) prepared in alkaline morpholinoethane sulfonic acid (MES) aqueous solution is that the cross-linking rate between the polymer and the collagen is low. To solve this problem, ethanol has been adopted as the reaction solvent, to prevent 1-ethyl-3-(3-dimethylaminopropyl)-1-carbodiimide hydrochloride (EDC) hydrolysis. Alterations in the ethanol mole concentration changed the cross-linking rate between the MPC polymer and the collagen gel. Prevention of EDC hydrolysis is clearly observed; protonation of carboxyl groups implies that the ratio of ethanol to water should be controlled. The polymer shows signs of penetration into the collagen gel layer, thus forming a totally homogeneous phase gel. This affects the mechanical strength of the collagen gel, making the gel much stiffer and brittle with an increase in the swelling ratio, as compared with that prepared in MES buffer. However, it is possible to obtain a collagen/phospholipid polymer hybrid gel with a high polymer portion and the cross-linking rate can be successfully controlled.     

Dengue fever virus and Japanese encephalitis virus synthetic peptides,with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions,can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)—A novel approach to the protection of humans

Flaviviruses were reported to induce CD8⁺ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules. The assembled HLA class I molecules are transported to the plasma membrane and prime CD8⁺ T cells. Current knowledge of the interaction of viral peptides with HLA molecules is reviewed. Based on this review, an idea is presented to use synthetic flavivirus peptides with an amino acid motif to fit with the HLA class I peptide binding group of HLA haplotypes prevalent in a given population in an endemic area. These synthetic viral peptides may be introduced into the human skin using a lotion containing the peptides (Peplotion) together with substances capable of enhancing the penetration of these peptides into the skin to reach Langerhans cells. The peptide-treated Langerhans cells, professional antigen-presenting cells, may bind the synthetic viral peptides by their HLA class I peptide-binding grooves. Antigens carrying Langerhans cells are able to migrate and induce the cellular immune response in the lymph nodes. This approach to the priming of antiviral CD8⁺ cytotoxic T cells may provide cellular immune protection from flavivirus infection without inducing the humoral immune response, which can lead to the shock syndrome in Dengue fever patients. To be able to develop anti-Dengue virus synthetic peptides for populations with different HLA class I haplotypes, it is necessary to develop computational studies to design HLA class I Dengue virus synthetic peptides with motifs to fit the HLA haplotypes of the population living in an endemic region for Dengue fever. Experiments to study Dengue virus and Japanese encephalitis peptides vaccines and their effectiveness in protection against Dengue fever and Japanese encephalitis are needed. The development of human antiviral vaccines for application of viral peptides in a lotion to human skin (Peplotion) may be useful and affordable for populations of developing countries.