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Part count reduction through part combination is a recognized goal of design for assembly (DFA). Some of the many benefits of part count reduction are: a reduced number of assembly operations, reduced procurement costs, cycle time reduction, supply chain reduction, and higher potential profits. In previous work, force flow analysis, a new technique to map forces as they flow across interfaces in a product, was shown to be successful at systematically providing creative insights for part combination. These insights arise by highlighting components having no relative motion between them. This paper presents a novel concept that extends the theoretical basis of force flow analysis to a much broader scope, referred to as effort flow analysis, addressing component combinations having varying degrees of relative motion. A systematic method for classifying these sets of components is given, and compliant mechanisms are presented as an example of successful combinations across interfaces with relative motion. Examples are provided for the redesign of a ‘Quick Grip™ Clamp’ and a staple remover, both of which highlight a specific class of relative motion components. [Copyright &y& Elsevier]

The purpose of this study was to determine the effects of constraining arm swing on the vertical displacement of the body's center of mass (COM) during treadmill walking and examine several common gait variables that may account for or mask differences in the body's COM motion with and without arm swing. Participants included 20 healthy individuals (10 male, 10 female; age: 27.8 ± 6.8 years). The body's COM displacement, first and second peak vertical ground reaction forces (VGRFs), and lowest VGRF during mid-stance, peak summed bilateral VGRF, lower extremity sagittal joint angles, stride length, and foot contact time were measured with and without arm swing during walking at 1.34 m/s. The body's COM displacement was greater with the arms constrained (arm swing: 4.1 ± 1.2 cm, arm constrained: 4.9 ± 1.2 cm, p < 0.001). Ground reaction force data indicated that the COM displacement increased in both double limb and single limb stance. However, kinematic patterns visually appeared similar between conditions. Shortened stride length and foot contact time also were observed, although these do not seem to account for the increased COM displacement. However, a change in arm COM acceleration might have contributed to the difference. These findings indicate that a change in arm swing causes differences in vertical COM displacement, which could increase energy expenditure. [ABSTRACT FROM AUTHOR]

This case report describes a child who developed Pott's puffy tumor and was treated at the Children's Mercy Hospital in Kansas City. In addition to a discussion of a case, a review of the literature was completed on this topic describing the typical embryology and development of the frontal sinus, and the epidemiology, diagnosis, and treatment of Pott's puffy tumor. The patient was a 23-month-old boy who developed Pott's puffy tumor after recovery from influenza. The patient presented to the hospital with progressing edema of the unilateral eye that spread bilaterally within a few days. A CT scan demonstrated pansinusitis, developed frontal sinuses, right periorbital cellulitis, and medial forehead subperiosteal abscess. Functional endoscopic sinus surgery and transcutaneous abscess drainage were urgently performed and the patient made a full recovery following a course of ertapenem and levofloxacin. The presence of a developed frontal sinus in a 23-month-old is an unexpected radiologic finding. This case represents the youngest patient reported in the literature to develop this rare complication of frontal sinusitis. [ABSTRACT FROM AUTHOR]

Severe Plasmodium falciparum malaria infections are caused by microvascular sequestration of parasites binding to the human endothelial protein C receptor (EPCR) via the multi-domain P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion ligands. Using cryogenic electron microscopy (Cryo-EM) and PfEMP1 sequence diversity analysis, we found that group A PfEMP1 CIDRα1 domains interact with the adjacent DBLα1 domain through central, conserved residues of the EPCR-binding site to adopt a compact conformation. Upon EPCR binding, the DBLα1 domain is displaced, and the EPCR-binding helix of CIDRα1 is turned, kinked, and twisted to reach a rearranged, stable EPCR-bound conformation. The unbound conformation and the required transition to the EPCR-bound conformation may represent a conformational masking mechanism of immune evasion for the PfEMP1 family. [Display omitted] • N-terminal domains of severe malaria-associated group A PfEMP1 form an entity • DBLα1 and CIDRα1 domains interact through the EPCR-binding site on CIDRα1 • The packing of the domains may confer immune evasion to the conserved EPCR-binding site • EPCR binding displaces DBLα1 and induces conformational changes in CIDRα1 Severe malaria is caused by parasites binding to the human endothelial protein C receptor (EPCR) through CIDRα1-containing PfEMP1. Here, Raghavan et al. show how EPCR engagement induces a large conformational change to the CIDRα1 domain when opening the otherwise compact N-terminal DBLα1-CIDRα1 complex partially hiding the conserved EPCR-binding site. [ABSTRACT FROM AUTHOR]

Aim: Central arterial hemodynamics is associated with cognitive impairment. Reductions in gait speed during walking while performing concurrent tasks known as dual-tasking (DT) or multi-tasking (MT) is thought to reflect the cognitive cost that exceeds neural capacity to share resources. We hypothesized that central vascular function would associate with decrements in gait speed during DT or MT.Methods: Gait speed was measured using a motion capture system in 56 women (30-80y) without mild-cognitive impairment. Dual-tasking was considered walking at a fast-pace while balancing a tray. Multi-tasking was the DT condition plus subtracting by serial 7's. Applanation tonometry was used for measurement of aortic stiffness and central pulse pressure. Doppler-ultrasound was used to measure blood flow velocity and β-stiffness index in the common carotid artery.Results: The percent change in gait speed was larger for MT than DT (14.1±11.2 vs. 8.7±9.6%, p <0.01). Tertiles were formed based on the percent change in gait speed for each condition. No vascular parameters differed across tertiles for DT. In contrast, carotid flow pulsatility (1.85±0.43 vs. 1.47±0.42, p=0.02) and resistance (0.75±0.07 vs. 0.68±0.07, p=0.01) indices were higher in women with more decrement (third tertile) as compared to women with less decrement (first tertile) in gait speed during MT after adjusting for age, gait speed, and task error. Carotid pulse pressure and β-stiffness did not contribute to these tertile differences.Conclusion: Elevated carotid flow pulsatility and resistance are characteristics found in healthy women that show lower cognitive capacity to walk and perform multiple concurrent tasks. [ABSTRACT FROM AUTHOR]

Aim: Cognitive dysfunction is associated with slower gait speed in older women, but whether cognitive function affects gait performance earlier in life has yet to be investigated. Thus, the objective of this study was to test the hypothesis that cognitive function will discriminate gait performance in healthy younger women.Methods: Fast-pace and dual-task gait speed were measured in 30 young to middle-aged (30-45y) and 26 older (61-80y) women without mild cognitive impairment. Visuoperceptual ability, working memory, executive function, and learning ability were assessed using neuropsychological tests. Within each age group, women were divided by the median into lower and higher cognitive function groups to compare gait performance.Results: Younger women with higher visuoperceptual ability had faster fast-pace (2.25±0.30 vs. 1.98±0.18m/s, p≤0.01) and dual-task gait speed (2.02±0.27 vs. 1.69±0.25m/s, p≤0.01) than women with lower visuoperceptual ability. The difference in dual-task gait speed remained significant (p=0.02) after adjusting for age, years of education, and other covariates. Dividing younger women based on other cognitive domains showed no difference in gait performance. In contrast, working memory and executive function discriminated dual-task gait speed (p<0.05) in older women after adjusting for age and education.Conclusion: To our knowledge, this is the first study to show that poorer cognitive function even at a relatively young age can negatively impact mobility. Different cognitive functions discriminated gait performance based on age, highlighting a possible influence of aging in the relationship between cognitive function and mobility in women. [ABSTRACT FROM AUTHOR]

Mutations in cancer can cells may lead to the formation of neo-epitopes potentially presented by both major histocompatibility complex (MHC) class I or II. These neo epitopes may be recognized by CD8+ or CD4+ T-cells, and trigger an immune response. Only a small fraction of the neo-epitopes will be displayed by the MHC class I or II. One of the challenges of cancer immuno-therapy is therefore to predict which neo-epitopes are susceptible to elicit a T cell response. Software tools such as netMHC, Mhc Flury and many others are over-predictive as the bulk part of the data used to train these methods are based on affinity assays. Several publications have indicated that stability assays may be better to train prediction tools for epitope presentation by MHC, therefore paving the way to effective cancer vaccine design. We performed stability assay measurements through our Neoscreen platform for 10 MHC class I and 10 MHC class II alleles using a peptide scan library approach. The data is used to train a prediction tool, PrDx, that relies on a combination of different machine learning methods (random forest, feed forward neural networks and recurrent neural networks), of which the outputs are gathered in an assemble model, able to predict T-cell epitopes, based on both stability and affinity data. The models are then further trained with peptides predicted to have strong stability, until satisfactory performances are attained. Our method is able to further filter potential peptides for cancer vaccine design, compared to state-of-the-art epitope prediction methods. The PrDx and NeoScreen platforms have been applied in a first patient case where 20,000 mutations were identified, with 40 of the most likely neoepitopes being selected. The patient is expected to be treated in April/May 2019. [ABSTRACT FROM AUTHOR]

Invasive fungal rhinosinusitis (IFRS) is a potentially fatal disease that affects the severely immunocompromised and requires aggressive treatment. The objective of this study is to better describe predictors of biopsy positivity in patients at high risk of IFRS at a pediatric hospital. This was a single-center case-control study of 36 patients (37 total biopsies) ≤ 21 years old with one of five high-risk oncologic/hematologic diagnoses who underwent operative endoscopy for clinical suspicion for IFRS. IFRS positivity was defined histologically. Collected information included patient demographics, primary diagnosis, oncologic relapses, time from diagnosis to biopsy, clinical characteristics, and endoscopic findings. These data were used to create a simple predictive scoring system. 17 patients had biopsy-proven IFRS (IFRS(+)) for an overall incidence of 2.1% in the designated high-risk population. Average time from most recent oncologic development (diagnosis, relapse, or hematopoietic stem-cell transplant) to biopsy in the IFRS(+) group was 2.09 months (SD = 2.26), and 7.28 months in the IFRS(−) group (SD = 9.17) (p = 0.009). Clinical characteristics did not differentiate between IFRS(+) and IFRS(−). Bedside endoscopy performed poorly, as it was interpreted as normal in 42.8% of IFRS(+) and 53.8% of IFRS(−). In contrast, the presence of any positive endoscopic finding intra-operatively was highly specific for IFRS(+) (94%) with moderate sensitivity (70%), and the difference in rate of positivity between groups was statistically significant (p < 0.001). Operative endoscopy with biopsy remains the gold-standard to rule-out IFRS in the setting of high clinical suspicion. Time elapsed from most recent oncologic development to clinical concern for IFRS may influence the likelihood of disease, though this requires further study. Clinical symptoms and bedside endoscopy were not predictive and should be used with caution in decision-making. [ABSTRACT FROM AUTHOR]

The article presents a medical research study examining the volume deficits of parietal lobe volume within early-onset schizophrenic adolescents and adolescents with Cannabis use disorders. The cerebral cortical gray matter structure of both groups is then characterized through T1-weighted magnetic resonance images. Preliminary conclusions on the interrelation of the two disorders are then provided.

Tracheostomy in children is often performed to alleviate airway obstruction (AO) or to facilitate long-term ventilator support due to respiratory failure of various etiologies, such as heart failure, and postoperative respiratory failure. Although many of these pathologies are common among trisomy 21 patients, tracheostomy rates among this population have not previously been reported. The aim of our study was to determine the incidence of trisomy 21 patients undergoing tracheostomy. Secondary objectives include decannulation rates and mortality associated with tracheostomy. A retrospective cohort study was conducted on pediatric trisomy 21 patients undergoing tracheostomy between 2004 and 2013. Twenty patients underwent tracheostomy at a median age of 7.1 months (interquartile range [IQR] = 3.5,21.3). The estimated incidence of tracheostomy in trisomy 21 patients among our tracheostomy population was 1.7% (20/1173) over 10 years. The most common indications were airway obstruction (AO) (55%), cardiac/pulmonary respiratory failure (CRF) (25%), or both (20%). Overall mortality was 30%, much lower among AO patients (9%) than CRF (40%) or both (60%), (P = 0.029). Nine patients (45%) were successfully decannulated, with median duration of cannulation of 2.2 years (IQR = 1.7,3). This study suggests a rate of tracheostomy in the pediatric trisomy 21 population approximately 3 times that of the general pediatric population. Over half in this cohort underwent tracheostomy for isolated AO, while the general pediatric tracheostomy population demonstrates a much higher prevalence of prematurity-related CRF. Overall mortality rate and decannulation rate approximated that of the general pediatric tracheostomy population, although outcomes were significantly poorer among patients trisomy 21 patients undergoing tracheostomy for CRF. [ABSTRACT FROM AUTHOR]

Coastal ecosystem studies using remote visible/infrared spectroscopy typically invert an atmospheric model to estimate the water-leaving reflectance signal. This inversion is challenging due to the confounding effects of turbid backscatter, atmospheric aerosols, and sun glint. Simultaneous estimation of the surface and atmosphere can resolve the ambiguity enabling spectral reflectance maps with rigorous uncertainty quantification. We demonstrate a simultaneous retrieval method that adapts the Optimal Estimation (OE) formalism of Rodgers (2000) to the coastal domain. We compare two surface representations: a parametric bio-optical model based on Inherent Optical Properties (IOPs); and an expressive statistical model that estimates reflectance in every instrument channel. The latter is suited to both land and water reflectance, enabling a unified analysis of terrestrial and aquatic domains. We test these models with both vector and scalar Radiative Transfer Models (RTMs). We report field experiments by two airborne instruments: NASA's Portable Remote Imaging SpectroMeter (PRISM) in an overflight of Santa Monica, California; and NASA's Next Generation Airborne Visible Infrared Imaging Spectrometer (AVIRIS-NG) in an overflight of the Wax Lake Delta and lower Atchafalaya River, Louisiana. In both cases, in situ validation measurements match remote water-leaving reflectance estimates to high accuracy. Posterior error predictions demonstrate a closed account of uncertainty in these coastal observations. • We adapt Optimal Estimation (OE) methods to VSWIR coastal imaging spectroscopy. • OE enables simultaneous surface and atmosphere retrieval with uncertainty estimates. • We compare surface parameterizations suited for land, deep water, and turbid water. • We perform field tests with multiple airborne imaging spectrometer field campaigns. • Remote reflectance accurately matches in situ validation measurements. [ABSTRACT FROM AUTHOR]