Team IHMC at the 2020 Cybathlon: a user-centered approach towards personal mobility exoskeletons.

BACKGROUND: The past few decades have seen rapid advancements in exoskeleton technology, with a considerable shift towards applications involving users with gait pathologies. Commercial devices from ReWalk, Ekso Bionics, and Indego, mainly designed for rehabilitation purposes, have inspired the development of many research platforms aimed at extending capabilities for use as safe and effective personal mobility devices. The 2016 Cybathlon featured an impressive demonstration of exoskeletons designed to enable mobility for individuals with spinal cord injury, however, not a single team completed every task and only two completed the stairs. Major improvements were showcased at the 2020 Cybathlon, with seven of the nine teams completing a similar set of tasks. Team IHMC built upon its silver-medal success from 2016 with an upgraded device, Quix. METHODS: Quix features several notable improvements including an additional powered degree of freedom for hip ab/adduction to laterally shift the device and reduce user effort while walking, custom-tailored cuffs and soft goods based on 3D body scans to optimize user comfort, and a streamlined testing pipeline for online tuning of gait parameters. RESULTS: Team IHMC finished in fourth place behind the teams from EPFL and Angel Robotics. Although we suffered from a considerably slower flat-ground walking speed, our pilot reported marked improvements in overall effort, comfort, and ease-of-use compared to our previous device. CONCLUSIONS: Clear progress in exoskeleton development has been exhibited since the inaugural Cybathlon, with tasks involving rough terrain, stairs, and ramps now posing little threat to most of the competitors. As a result, the layout of the powered exoskeleton course will likely undergo significant modifications to further push the devices towards suitability for personal everyday use. The current tasks do not address the issue of donning and doffing, nor do they simulate a scenario similar to maneuvering a kitchen to prepare a meal, for example. An additional limitation that may be more difficult to test in a competition setting is the required upper-body effort to manipulate the device in an effective manner.

Molecular cytogenetic differentiation of paralogs of Hox paralogs in duplicated and re-diploidized genome of the North American paddlefish (Polyodon spathula).

BACKGROUND: Acipenseriformes is a basal lineage of ray-finned fishes and comprise 27 extant species of sturgeons and paddlefishes. They are characterized by several specific genomic features as broad ploidy variation, high chromosome numbers, presence of numerous microchromosomes and propensity to interspecific hybridization. The presumed palaeotetraploidy of the American paddlefish was recently validated by molecular phylogeny and Hox genes analyses. A whole genome duplication in the paddlefish lineage was estimated at approximately 42 Mya and was found to be independent from several genome duplications evidenced in its sister lineage, i.e. sturgeons. We tested the ploidy status of available chromosomal markers after the expected rediploidization. Further we tested, whether paralogs of Hox gene clusters originated from this paddlefish specific genome duplication are cytogenetically distinguishable. RESULTS: We found that both paralogs HoxA alpha and beta were distinguishable without any overlapping of the hybridization signal - each on one pair of large metacentric chromosomes. Of the HoxD, only the beta paralog was unequivocally identified, whereas the alpha paralog did not work and yielded only an inconclusive diffuse signal. Chromosomal markers on three diverse ploidy levels reflecting different stages of rediploidization were identified: quadruplets retaining their ancestral tetraploid condition, semi-quadruplets still reflecting the ancestral tetraploidy with clear signs of advanced rediploidization, doublets were diploidized with ancestral tetraploidy already blurred. Also some of the available microsatellite data exhibited diploid allelic band patterns at their loci whereas another locus showed more than two alleles. CONCLUSIONS: Our exhaustive staining of paddlefish chromosomes combined with cytogenetic mapping of ribosomal genes and Hox paralogs and with microsatellite data, brings a closer look at results of the process of rediploidization in the course of paddlefish genome evolution. We show a partial rediploidization represented by a complex mosaic structure comparable with segmental paleotetraploidy revealed in sturgeons (Acipenseridae). Sturgeons and paddlefishes with their high propensity for whole genome duplication thus offer suitable animal model systems to further explore evolutionary processes that were shaping the early evolution of all vertebrates.

Examining the Role of Quality of Institutionalized Healthcare on Maternal Mortality in the Dominican Republic.

The main study objective was to determine the extent to which the quality of institutionalized healthcare, sociodemographic factors of obstetric patients, and institutional factors affect maternal mortality in the Dominican Republic. COM-Poisson distribution and the Pearson correlation coefficient were used to determine the relationship of predictor factors (i.e., hospital bed rate, vaginal birth rate, teenage mother birth rate, single mother birth rate, unemployment rate, infant mortality rate, and sex of child rate) in influencing maternal mortality rate. The factors hospital bed rate, teenage mother birth rate, and unemployment rate were not correlated with maternal mortality. Maternal mortality increased as vaginal birth rates and infant death rates increased whereas it decreased as single mother birth rates increased. Further research to explore alternate response variables, such as maternal near-misses or severe maternal morbidity is warranted. Additionally, the link found between infant death and maternal mortality presents an opportunity for collaboration among medical specialists to develop multi-faceted solutions to combat adverse maternal and infant health outcomes in the DR.

The Environmental and Social Determinants of Health Matter in a Pandemic: Predictors of COVID-19 Case and Death Rates in New York City.

Our research objective was to determine which environmental and social factors were predictive of coronavirus disease 2019 (COVID-19) case and death rates in New York City (NYC), the original epicenter of the pandemic in the US, and any differential impacts among the boroughs. Data from various sources on the demographic, health, and environmental characteristics for NYC zip codes, neighborhoods, and boroughs were analyzed along with NYC government's reported case and death rates by zip code. At the time of analysis, the Bronx had the highest COVID-19 case and death rates, while Manhattan had the lowest rates. Significant predictors of a higher COVID-19 case rate were determined to be proportion of residents aged 65 years plus; proportion of residents under 65 years with a disability; proportion of White residents; proportion of residents without health insurance; number of grocery stores; and a higher ozone level. For COVID-19 death rates, predictors include proportion of residents aged 65 years plus; proportion of residents who are not US citizens; proportion on food stamps; proportion of White residents; proportion of residents under 65 years without health insurance; and a higher level of ozone. Results across boroughs were mixed, which highlights the unique demographic, socioeconomic, and community characteristics of each borough. To reduce COVID-19 inequities, it is vital that the NYC government center the environmental and social determinants of health in policies and community-engaged interventions adapted to each borough.

Wnt3 signaling in the epiblast is required for proper orientation of the anteroposterior axis.

The establishment of anteroposterior (AP) polarity in the early mouse epiblast is crucial for the initiation of gastrulation and the subsequent formation of the embryonic (head to tail) axis. The localization of anterior and posterior determining genes to the appropriate region of the embryo is a dynamic process that underlies this early polarity. Several studies indicate that morphological and molecular markers which define the early AP axis are first aligned along the short axis of the elliptical egg cylinder. Subsequently, just prior to the time of primitive streak formation, a conformational change in the embryo realigns these markers with the long axis. We demonstrate that embryos lacking the signaling factor Wnt3 exhibit defects in this axial realignment. In addition, chimeric analyses and conditional removal of Wnt3 activity reveal that Wnt3 expression in the epiblast is required for induction of the primitive streak and mesoderm whereas activity in the posterior visceral endoderm is dispensable.

Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits.

The angiotensin II type 1 receptor (AGTR1) is the main target through which angiotensin II influences cardiovascular tone, cell growth, and fluid and electrolyte balance. AGTR1 polymorphism has been reported to associate with hypertension, myocardial infarction (MI), and metabolic traits. Here we describe a novel approach to quantitation of transcript haplotypes (QTH) of AGTR1. To determine relative allelic expression from haplotypes, within-individual-between-allele ratiometric analyses in placental cDNA were developed for the transcribed SNPs rs5182:C>T (encoding p.L191) and rs5186:A>C (3'-noncoding "A1166C"). Additionally, between-individual comparisons were made using TaqMan assays applied to both homozygous and heterozygous genotypes and haplotypes. In conjunction, linkage disequilibrium (LD) and genomic haplotype associations with metabolic syndrome were examined. There was no significant difference of mRNA level for alleles of rs5182:C>T, but allele and mRNA haplotypes carrying 1166C exhibited reduced abundance. The effect was much greater in CC homozygotes than in heterozygotes. The promoter region was confirmed to be in a separate haplotype block from the AGTR1 3' region containing rs5182:C>T and rs5186:A>C. Metabolic syndrome trait associations were strongest for the 3' block generally and for the C allele of rs5186:A>C specifically. All effects were much more prominent in homozygotes, possibly reflecting interallelic interaction through feedback loops of mRNA regulation. Differential abundance of AGTR1 mRNA haplotypes may mediate clinical phenotypic observations of the AGTR1 genotype.

Dietary supplementation with fish oil modifies the ability of human monocytes to induce an inflammatory response.

Monocytes/macrophages are key orchestrators of inflammation and are involved in the pathogenesis of chronic inflammatory disorders, including atherosclerosis. (n-3) Fatty acids, found in fish oil, have been shown to have protective effects in such disorders. To investigate possible modes of action, we used a monocyte:endothelial cell (EC) coculture model to investigate the pro-inflammatory potential of monocytes. Monocytes were isolated from the blood of donors with peripheral arterial disease (PAD) or control donors, before and after a 12-wk supplementation of their diet with fish oil. The monocytes were cultured with human umbilical vein EC (HUVEC) for 24 h, after which the ability of the HUVEC to recruit flowing neutrophils was tested. Monocytes from either group of donors stimulated the EC to support the adhesion and migration of neutrophils. Fish oil supplementation reduced the potency of monocytes from normal subjects, but not those from patients with PAD, to induce recruitment. Concurrent medication may have acted as a complicating factor. On subgroup analysis, only those free of medication showed a significant effect of fish oil. Responses before or after supplementation were not closely linked to patterns of secretion of cytokines by cultured monocytes, tested in parallel monocultures. These results suggest that fish oil can modulate the ability of monocytes to stimulate EC and that this might contribute to their protective effects against chronic inflammatory disorders. Benefits, however, may depend on existing medical status and on other treatments being received.

Alcohol screening instruments and psychiatric evaluation outcomes in military aviation personnel.

INTRODUCTION: Alcohol-related disorders are the most prevalent psychiatric conditions in the aviation population. Efforts to effectively screen aviators for these disorders are continually sought, as underdiagnosis may negatively impact aviation safety. This study evaluates screening tools that have been validated in non-aviators in terms of their utility for aviator patients. METHODS: There were 111 male aviation patients (27 +/- 7 yr) referred for psychiatric evaluation at the Naval Aerospace Medicine Institute who completed the Self-Administered Alcohol Screening Test (SAAST), the Alcohol-Use Disorders Identification Test (AUDIT), and the Common Alcohol Logistical Scale-Revised (CAL-R) prior to evaluation by a staff psychiatrist or psychologist. RESULTS: There were 40 patients who were qualified psychiatrically with no diagnosis and 49 patients who were disqualified for psychiatric reasons due to a non alcohol-related diagnosis. The remaining 22 patients were disqualified for psychiatric reasons with an alcohol-related diagnosis. The optimal aviator cut-off scores were consistent with those of the general population, although the cut-off score used for the SAAST was set at the published sub-threshold level to provide greater sensitivity. The sensitivity/specificity values for the SAAST, AUDIT, and CAL-R were 59%/94%, 46%/96%, and 68%/81%, respectively. CONCLUSION: The psychometrically sophisticated CAL-R is sensitive, specific, and has good negative predictive value, although its use requires a psychologist and its availability is limited. The SAAST and AUDIT can be administered by a flight surgeon or aviation medical examiner (AME). Given the higher sensitivity of the SAAST it may be the most beneficial if administered first. The AUDIT can be used as a follow-up diagnostic test given its higher specificity.

The hemophagocytic syndrome: titrating continuous hemofiltration to the degree of lactic acidosis.

In 3 cases of severe multiple organ failure due to hemophagocytic lymphohistiocytosis (HLH) in children, the authors demonstrate the utility of continuous hemofiltration in attenuating the consequences of excess cytokine activity, with therapy titrated to the degree of lactic acidosis. HLH was diagnosed in 3 encephalopathic children with multiple organ failure, elevated ferritin (49,396-237,582 pmol/L; or 21,983-105,733 ng/mL), elevated serum triglyceride, and depressed cell lines. One had a known malignancy, one had EBV-associated lymphoproliferative disease, and one was previously healthy. Continuous hemofiltration was initiated, with the ultrafiltrate production rate and countercurrent dialysate flow titrated to metabolic acidosis as reflected by the serum lactate (maximum 3.5 mmol/L or 31.6 mg/dL). Hemofiltration was titrated upward until lactic acidosis resolved, through clearance of lactate or interruption of excess cytokine-driven activity; maximum prescription was 2000 mL/h ultrafiltrate production plus 2500 mL/h dialysate flow. Stability was achieved with hemofiltration, then substantial resolution occurred with treatment according to the HLH-94 protocol (dexamethasone, cyclosporin, VP-16, intrathecal methotrexate). One child succumbed to candidiasis. Another made a full recovery. A third succumbed to his primary malignancy. HLH should be suspected in unexplained or unresolving multiple organ failure. Titration of hemofiltration based on measurable parameters of cellular metabolism (e.g., lactate, base deficit) may stabilize the child with metabolic acidosis long enough to allow proper diagnosis and institution of definitive therapy. Hemofiltration is not a panacea but rather a stabilizing mechanism, with poorly understood effects on interstitial water and solute flux, that facilitates recovery over weeks, not days.

Role of single nucleotide polymorphisms of pro-inflammatory cytokine genes in the relationship between serum lipids and inflammatory parameters, and the lipid-lowering effect of fish oil in healthy males.

BACKGROUND AND AIMS: Lipid metabolism, obesity and inflammation are intimately related. Plasma triglycerides increase during the inflammatory response to pathogens and obesity increases inflammatory stress. Pro-inflammatory cytokines are secreted by adipocytes in uninfected obese subjects. Polymorphisms (SNPs) in cytokine genes influence the intensity of cytokine production and inflammatory stress. Fish oil has lipid-lowering and anti-inflammatory properties. The influence of cytokine gene polymorphisms on the interaction between adiposity, inflammation and the properties of fish oil is unknown. METHODS: Fasting plasma triglycerides, acute phase proteins and BMI were studied in 159 healthy men and the effect of 6 g/d fish oil for 12 weeks on the former two parameters studied. Subjects were genotyped for SNPs at positions -511, -174, +252 and -308 in the IL-1beta, IL-6, LT-alpha (TNF-beta) and TNF-alpha genes, respectively. Data were divided into three sub-groups of BMI, 16.7-22.8, 22.9-24.9 and 25.1-33.7 kg/m2, respectively. RESULTS: Correlations were apparent between CRP and triglycerides in the highest tertile r = 0.324, P < 0.05 and between CRP and serum amyloid in all tertiles. Mean concentrations of all three molecules were higher in the middle and highest tertile than in the lowest. Irrespective of BMI, CRP and triglycerides were positively correlated in subjects with a TNF-alpha-308GG, LT-alpha AG, IL-1beta-511TT and IL-6-174GG genotype. The latter three genotypes are associated with enhanced inflammation. Genotype and BMI interacted. Concentrations of triglyceride rose significantly with increasing tertile only in subjects with a LT-alpha AA genotype. CRP concentrations rose in subjects with a LT-alpha AG genotype. Triglycerides were lowered by fish oil. Pre-supplementation concentrations were correlated with the decrease, r = -0.494 P < 0.0001. Genotype influenced the effects of fish oil. A fall occurred in triglycerides, across tertiles of BMI, only in individuals possessing a LT-alpha+252 AA genotype. Irrespective of BMI, possession of an A allele of this SNP was necessary for the correlation to occur. CONCLUSIONS: Possession of genotypes associated with raised inflammatory stress strengthen the association between fasting plasma triglycerides and CRP. The ability of fish oil to exert a lipid-lowering, anti-inflammatory influence in healthy men is influenced by BMI and possession of the LT-alpha+252 A allele.

Osteomyelitis: an update for hospitalists.

Osteomyelitis is a common and challenging condition for hospitalists to manage. The 3 main types of osteomyelitis that are commonly seen in the hospital setting are 1) contiguous spread from decubitus or diabetic ulcers, 2) hematogenous spread, such as in vertebral or long bone metaphyses, and 3) infections associated with a prosthetic joint. In patients with diabetes, osteomyelitis is the underlying cause of about 20% of foot infections, and greatly increases the chance that the patient will eventually need an amputation and be subject to perioperative risks. Osteomyelitis from hematogenous spread is increasing. The prevalence of vertebral osteomyelitis is also increasing, particularly in intravenous drug users and patients treated with immune-modulating agents. Prosthetic joint infections are perhaps the most challenging type to treat, and require hospitalists, orthopedic surgeons, and infectious disease specialists to work closely together to plan for effective treatment. Due to increasing antibiotic resistance, the microorganisms involved are also proving more difficult to treat. Emerging resistance to the commonly used antibiotics is resulting in changes in treatment choices. Community-acquired methicillin-resistant Staphylococcus aureus is commonly seen, and there is increasing concern about emerging vancomycin resistance. Treatment of osteomyelitis is still based largely on expert opinion rather than evidence from controlled studies.

Human Factors in the 1990s: sealing transition cracks.

This is an account of my 8-year tour as Human Factors editor during the last decade of the past century. I accepted this appointment with the understanding that the journal, although highly successful, was entering a period of transition during which problems were surfacing that would require some strategic redirection. Together with Human Factors and Ergonomics Society staff and my editorial board, which in addition to peer review I relied on heavily for advice on journal policy, we effected a number of changes. In this article, I review those changes along with the issues they were designed to address and the reasoning behind each. It remains for the reader to judge whether the net effect of these changes has been for the better.

CNS T-cell lymphoma: an under-recognized entity?

The incidence of CNS lymphoma has increased significantly in the past 30 years, primarily in the elderly and immunocompromised. While T-cell lymphomas comprise 15-20% of systemic lymphomas, they comprise less than 4% of primary CNS lymphomas, suggesting that they may be under-recognized compared to their systemic counterparts. To investigate this, we studied brain biopsies from three patients who were diagnosed with T-cell lymphoma confined to the brain. They had enhancing lesions by MRI, arising in the cerebellum and brainstem in one and temporal lobe in two. We compared these to biopsies from three patients who had reactive lymphoid infiltrates and who had clinical signs/symptoms and radiographic findings that were indistinguishable from the lymphoma group. Biopsies from both the lymphoma group and reactive group showed considerable cytomorphologic heterogeneity. Although one lymphoma case contained large atypical cells, the other two contained small, mature lymphocytes within a heterogeneous infiltrate of neoplastic and reactive inflammatory cells. Surface marker aberrancies were present in two lymphoma cases, but this alone could not reliably diagnose T-cell lymphoma. The proliferation index was not useful for differentiating lymphoma from reactive infiltrates. In five of the six cases the diagnosis was most influenced by clonality studies for T-cell receptor-gamma gene rearrangements. We conclude that because of the high degree of overlap in cytomorphologic and immunophenotypic features between T-cell lymphoma and reactive infiltrates, T-cell lymphoma may not be recognized unless studies for T-cell receptor gene rearrangements are performed for CNS lesions composed of a polymorphous but predominantly T-cell infiltrate.