Hox11-expressing interstitial cells contribute to adult skeletal muscle at homeostasis.

Interstitial stromal cells play critical roles in muscle development, regeneration and repair and we have previously reported that Hoxa11 and Hoxd11 are expressed in the interstitial cells of muscles attached to the zeugopod, and are crucial for the proper embryonic patterning of these muscles. Hoxa11eGFP expression continues in a subset of muscle interstitial cells through adult stages. The induction of Hoxa11-CreERT2-mediated lineage reporting (Hoxa11iTom) at adult stages in mouse results in lineage induction only in the interstitial cells. However, Hoxa11iTom+ cells progressively contribute to muscle fibers at subsequent stages. The contribution to myofibers exceeds parallel Pax7-CreERT2-mediated lineage labeling. Nuclear-specific lineage labeling demonstrates that Hoxa11-expressing interstitial cells contribute nuclear contents to myofibers. Crucially, at no point after Hoxa11iTom induction are satellite cells lineage labeled. When examined in vitro, isolated Hoxa11iTom+ interstitial cells are not capable of forming myotubes, but Hoxa11iTom+ cells can contribute to differentiating myotubes, supporting Hox-expressing interstitial cells as a new population of muscle progenitors, but not stem cells. This work adds to a small but growing body of evidence that supports a satellite cell-independent source of muscle tissue in vivo.

Do Women and Minority Orthopaedic Residents Report Experiencing Worse Well-being and More Mistreatment Than Their Peers?

BACKGROUND: Despite the increased risk of attrition for women and minority residents during orthopaedic residency, there is currently a paucity of research examining the training environment of these residents. To address this, we examined how well-being constructs may differ for women or minority residents compared with their peers, and whether these residents report experiencing more mistreatment during residency. QUESTIONS/PURPOSES: (1) How does the psychologic wellbeing of women and minority residents compare with that of their peers regarding the constructs of burnout, lifestyle satisfaction, social belonging, and stereotype threat? (2) Do reported mistreatment experiences during residency differ among women and minority residents compared with their peers? (3) Is there a difference in the proportion of women and minority orthopaedic residents with thoughts of leaving residency compared with their peers? METHODS: Seventeen orthopaedic residency programs in the 91 programs comprising the Collaborative Orthopaedic Educational Research Group agreed to participate in the study. Program directors sent an anonymous one-time survey with two reminders to all orthopaedic residents at their respective institutions. The survey instrument comprised validated and previously used instruments with face validity designed to measure burnout, satisfaction, duty-hour violations, belonging, stereotype threat, mistreatment, and thoughts of leaving residency, in addition to demographic information. Forty-three percent (211 of 491) of residents responded to the survey. Race or ethnicity data were combined into "White" and "underrepresented in orthopaedics" (URiO), which included residents who self-identified as Asian, African American, Hispanic or Latino, Native American, or other, given that these groups are all underrepresented racial and ethnic groups in orthopaedics. The demographic makeup of our study, 81% men and 75% White, is roughly comparable to the current demographic makeup of orthopaedic residency programs, which is 82% men and 74% White. Data were analyzed using chi-square tests, Fisher exact tests, and t-tests as appropriate. For comparisons of Likert scale measures, we used an anchor-based approach to determining the minimum detectable change (MDC) and set the MDC as a 1-point difference on a 5-point scale and a 1.5-point difference on a 7-point scale. Stereotype threat is reported as the mean ▵ from the neutral response, and ▵ of 1.5 or greater was considered significant. RESULTS: Women residents were more likely than men to report experiencing emotional exhaustion (odds ratio 2.18 [95% confidence interval 1.1 to 4.5]; p = 0.03). Women reported experiencing stereotype threat regarding their identity as women surgeons (mean ▵ 1.5 ± 1.0). We did not identify a difference in men's and women's overall burnout (OR 1.4 [95% CI 0.7 to 3.0]; p = 0.3), lifestyle satisfaction across multiple domains, or sense of social belonging (men: 4.3, women 3.6; mean difference 0.7 [95% CI 0.4 to 0.9]; p < 0.001). We did not identify differences in overall burnout (OR 1.5 [95% CI 0.8 to 3.0]; p = 0.2), lifestyle satisfaction across multiple domains, sense of social belonging (White: 4.2, URiO: 3.9; mean difference 0.3 [95% CI 0.17 to 0.61]; p < 0.001), or stereotype threat (mean ▵ 0.8 ± 0.9) between White and URiO surgeons. Women were more likely than men to report experiencing mistreatment, with 84% (32 of 38) of women and 43% (70 of 164) of men reporting mistreatment at least a few times per year (OR 7.2 [95% CI 2.8 to 18.1]; p < 0.001). URiO residents were more likely than White residents to report experiencing mistreatment overall, with 65% (32 of 49) of URiO residents and 45% (66 of 148) of White residents reporting occurrences at least a few times per year (OR 2.3 [95% CI 1.2 to 4.6]; p = 0.01). Women were more likely than men to report experiencing gender discrimination (OR 52.6 [95% CI 18.9 to 146.1]; p < 0.001), discrimination based on pregnancy or childcare status (OR 4.3 [95% CI 1.4 to 12.8]; p = 0.005), and sexual harassment (OR 11.8 [95% CI 4.1 to 34.3]; p < 0.001). URiO residents were more likely than White residents to report experiencing racial discrimination (OR 7.8 [95% CI 3.4 to 18.2]; p < 0.001). More women than men had thoughts of leaving residency (OR 4.5 [95% CI 1.5 to 13.5]; p = 0.003), whereas URiO residents were not more likely to have thoughts of leaving than White residents (OR 2.2 [95% CI 0.7 to 6.6]; p = 0.1). CONCLUSION: Although we did not detect meaningful differences in some measures of well-being, we identified that women report experiencing more emotional exhaustion and report stereotype threat regarding their identity as women surgeons. Women and URiO residents report more mistreatment than their peers, and women have more thoughts of leaving residency than men. These findings raise concern about some aspects of the training environment for women and URiO residents that could contribute to attrition during training. CLINICAL RELEVANCE: Understanding how well-being and mistreatment affect underrepresented residents helps in developing strategies to better support women and URiO residents during training. We recommend that orthopaedic governing bodies consider gathering national data on resident well-being and mistreatment to identify specific issues and track data over time. Additionally, departments should examine their internal practices and organizational culture to address specific gaps in inclusivity, well-being, and mechanisms for resident support.

Enantioselective Total Synthesis of (+)-Incargranine A Enabled by Bifunctional Iminophosphorane and Iridium Catalysis.

Herein we report the first enantioselective total synthesis of (+)-incargranine A, in nine steps. The total synthesis was enabled by an enantioselective intramolecular organocatalysed desymmetrising Michael addition of a malonamate ester to a linked dienone substrate that established pivotal stereocentres with excellent enantio- and complete diastereoselectivity. Furthermore, a key hemiaminal intermediate was accessed by developing an iridium-catalysed reductive cyclisation, and the scope of this transformation was explored to produce a range of bicyclic hemiaminal motifs. Once installed, the hemiaminal motif was used to initiate a biomimetic cascade to access the natural product directly in a single step.

Lumbopelvic fixation in the treatment of spinopelvic dissociation: union, complications, and neurologic outcomes of a multicenter case series.

PURPOSE: To review outcomes of spinopelvic dissociation treated with open lumbopelvic fixation. METHODS: We reviewed all cases of spinopelvic dissociation treated at three Level-I trauma centers with open lumbopelvic fixation, including those with adjunctive percutaneous fixation. We collected demographic data, associated injuries, pre- and postoperative neurologic status, pre- and postoperative kyphosis, and Roy-Camille classification. Outcomes included presence of union, reoperation rates, and complications involving hardware or wound. RESULTS: From an initial cohort of 260 patients with spinopelvic dissociation, forty patients fulfilled inclusion criteria with a median follow-up of 351 days. Ten patients (25%) had a combination of percutaneous iliosacral and open lumbopelvic repair. Average pre- and postoperative kyphosis was 30 degrees and 26 degrees, respectively. Twenty patients (50%) had neurologic deficit preoperatively, and eight (20%) were unknown or unable to be assessed. All patients presenting with bowel or bladder dysfunction (n = 12) underwent laminectomy at time of surgery, with 3 patients (25%) having continued dysfunction at final follow-up. Surgical site infection occurred in four cases (10%) and wound complications in two (5%). All cases (100%) went on to union and five patients (13%) required hardware removal. CONCLUSION: Open lumbopelvic fixation resulted in a high union rate in the treatment of spinopelvic dissociation. Approximately 1 in 6 patients had a wound complication, the majority of which were surgical site infections. Bowel and bladder dysfunction at presentation were common with the majority of cases resolving by final follow-up when spinopelvic dissociation had been treated with decompression and stable fixation.

Disentangling the intersection of inequities with health and malaria exposure: key lessons from rural communities in Northern Borneo.

BACKGROUND: The increasing incidence of Plasmodium knowlesi malaria poses a significant challenge to efforts to eliminate malaria from Malaysia. Macaque reservoirs, outdoors-biting mosquitoes, human activities, and agricultural work are key factors associated with the transmission of this zoonotic pathogen. However, gaps in knowledge regarding reasons that drive malaria persistence in rural Kudat, Sabah, Northern Borneo remain. This study was conducted to address this knowledge gap, to better understand the complexities of these entangled problems, and to initiate discussion regarding new countermeasures to address them. This study aims to highlight rural community members' perspectives regarding inequities to health relating to P. knowlesi malaria exposure. METHODS: From January to October 2022, a study using qualitative methods was conducted in four rural villages in Kudat district of Sabah, Malaysia. A total of nine in-depth interviews were conducted with community and faith leaders, after the completion of twelve focus group discussions with 26 photovoice participants. The interviews were conducted using the Sabah Malay dialect, audio-recorded, transcribed, and translated into English. The research team led the discussion and analysis, which was approved by participants through member checking at the community level. RESULTS: Participants identified disparity in health as a key issue affecting their health and livelihoods. Injustice in the social environment was also identified as a significant challenge, including the importance of listening to the voices of affected communities in disentangling the social and economic phenomena that can impact malaria control. Specific concerns included inadequate access to health-related resources and degradation of the environment. Participants recommended improving access to water and other necessities, increasing the availability of malaria control commodities in healthcare facilities, and developing sustainable programs to reduce socioeconomic disparities. CONCLUSION: Inequities to health emerged as a key concern for malaria control in rural Kudat, Sabah. A locally targeted malaria programme cantered on improving the social and economic disparities associated with health outcomes, could be a potential strategy for malaria prevention in such areas. Community-level perspectives gathered from this study can be used as a foundation for future discussions and dialogues among policymakers and community members for achieving greater transparency, improving social equity, and interoperability in addressing P. knowlesi malaria control.

Combining camera trap surveys and IUCN range maps to improve knowledge of species distributions.

Reliable maps of species distributions are fundamental for biodiversity research and conservation. The International Union for Conservation of Nature (IUCN) range maps are widely recognized as authoritative representations of species' geographic limits, yet they might not always align with actual occurrence data. In recent area of habitat (AOH) maps, areas that are not habitat have been removed from IUCN ranges to reduce commission errors, but their concordance with actual species occurrence also remains untested. We tested concordance between occurrences recorded in camera trap surveys and predicted occurrences from the IUCN and AOH maps for 510 medium- to large-bodied mammalian species in 80 camera trap sampling areas. Across all areas, cameras detected only 39% of species expected to occur based on IUCN ranges and AOH maps; 85% of the IUCN only mismatches occurred within 200 km of range edges. Only 4% of species occurrences were detected by cameras outside IUCN ranges. The probability of mismatches between cameras and the IUCN range was significantly higher for smaller-bodied mammals and habitat specialists in the Neotropics and Indomalaya and in areas with shorter canopy forests. Our findings suggest that range and AOH maps rarely underrepresent areas where species occur, but they may more often overrepresent ranges by including areas where a species may be absent, particularly at range edges. We suggest that combining range maps with data from ground-based biodiversity sensors, such as camera traps, provides a richer knowledge base for conservation mapping and planning.

Combinación de censos con fototrampas y mapas de extensión de la UICN para incrementar el conocimiento sobre la distribución de las especies Resumen Los mapas confiables de la distribución de las especies son fundamentales para la investigación y conservación de la biodiversidad. Los mapas de distribución de la Unión Internacional para la Conservación de la Naturaleza (UICN) están reconocidos como representaciones de autoridad de los límites geográficos de las especies, aunque no siempre se alinean con los datos actuales de su presencia. En los mapas recientes de área de hábitat (ADH), las áreas que no son hábitat han sido eliminadas de la distribución de la UICN para reducir los errores de comisión, pero su concordancia con la presencia actual de las especies tampoco ha sido analizada. Analizamos la concordancia entre la presencia registrada por los censos de fototrampas y pronosticamos la presencia a partir de los mapas de la UICN y de ADH de 510 especies de mamíferos de talla mediana a grande en 80 áreas de muestreo de fototrampas. Las cámaras detectaron sólo el 39% de las especies esperadas con base en la distribución de la UICN y los mapas de ADH en todas las áreas; el 85% de las disparidades con la UICN ocurrieron dentro de los 200 km a partir del borde de la distribución. Sólo el 4% de la presencia de las especies fue detectada por las cámaras ubicadas fuera de la distribución de la UICN. La probabilidad de disparidad entre las cámaras y la UICN fue significativamente mayor para los mamíferos de talla pequeña y para los especialistas de hábitat en las regiones Neotropical e Indomalaya y en áreas con doseles forestales más bajos. Nuestros hallazgos sugieren que los mapas de distribución y ADH pocas veces subrepresentan las áreas con presencia de las especies, pero con frecuencia pueden sobrerrepresentar la distribución al incluir áreas en donde las especies pueden estar ausentes, en particular los bordes de la distribución. Sugerimos que la combinación de los mapas de distribución con los sensores de biodiversidad en tierra, como las fototrampas, proporciona una base más rica de conocimiento para el mapeo y la planeación de la conservación.

Clinical Practice Guideline Recommendations in Pediatric Orthopaedic Injury: A Systematic Review.

BACKGROUND: Lack of adherence to recommendations on pediatric orthopaedic injury care may be driven by lack of knowledge of clinical practice guidelines (CPGs), heterogeneity in recommendations or concerns about their quality. We aimed to identify CPGs for pediatric orthopaedic injury care, appraise their quality, and synthesize the quality of evidence and the strength of associated recommendations. METHODS: We searched Medline, Embase, Cochrane CENTRAL, Web of Science and websites of clinical organizations. CPGs including at least one recommendation targeting pediatric orthopaedic injury populations on any diagnostic or therapeutic intervention developed in the last 15 years were eligible. Pairs of reviewers independently extracted data and evaluated CPG quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. We synthesized recommendations from high-quality CPGs using a recommendations matrix based on the GRADE Evidence-to-Decision framework. RESULTS: We included 13 eligible CPGs, of which 7 were rated high quality. Lack of stakeholder involvement and applicability (i.e., implementation strategies) were identified as weaknesses. We extracted 53 recommendations of which 19 were based on moderate or high-quality evidence. CONCLUSIONS: We provide a synthesis of recommendations from high-quality CPGs that can be used by clinicians to guide treatment decisions. Future CPGs should aim to use a partnership approach with all key stakeholders and provide strategies to facilitate implementation. This study also highlights the need for more rigorous research on pediatric orthopaedic trauma. LEVEL OF EVIDENCE: Level II-therapeutic study.

A Measurement System for the Environmental Load Assessment of a Scale Ship Model-Part II.

In the process of ship motion control system design, it is necessary to take into account the impact of environmental disturbances such as winds, waves and sea currents. The commonly used representatives of wave influences in this area are the unidirectional wave power spectral density functions describing sea waves of different form: long-crested, fully developed waves, developing wind waves or multi-modal waves (e.g., with swell). The existing standard PSD models describe the surge of open sea or ocean. However, they are inadequate in the case of control system testing of scale ship models for sailing in open water areas such as lakes or test pools. This paper presents a study of wind-generated wave PSD estimations for a small lake used as a test area for free-running scale ships. The publication provides a brief overview of the wave spectral density functions commonly used for control system design. A measurement instrument using the idea of a water-induced variable capacitance that works synchronously with the wind sensors is also described. The process of collected data analysis is presented. As a result of the study, a series of empirical spectral density functions of lake waves for different wind speeds are obtained. They correspond to the rescaled, two-parametric ITTC model.

Support for management actions to protect night sky quality: Insights from visitors to state and national park units in the U.S.

Light pollution is a global phenomenon where anthropogenic light sources continue to grow unabated, affecting both social and ecological systems. This is leaving parks and protected areas as some of the last vestiges of naturally dark environments for protecting views of the night sky. Yet, even parks and protected areas have outdoor lighting. Alternative lighting practices are needed to reduce or prevent light pollution from within parks. However, making parks darker may not be desirable for some visitors if they believe it will reduce navigability, safety, or restrict how they recreate (e.g., requiring the use of red-light flashlights after dark and before dawn). How visitors will respond to alternative lighting practices that park managers can implement is still unknown. We used an on-site intercept survey at nine state and national park units in Utah, U.S., to investigate nighttime visitors' support or opposition to management actions to protect night sky quality and their interest in learning about topics related to night skies. Further, this study also segmented visitors into two groups: those 'dependent' on the dark sky as a resource and those whose activities did not depend on a dark sky. Defining what a 'dark sky dependent' visitor is, which has yet to be done in the literature, is a fundamental step to furthering night sky research and management efforts. Across nine parks and protected areas, 62% of nighttime visitors participated in dark sky dependent activities. Findings indicate broad support for management actions designed to improve night sky quality, with between 74% and 89% of all visitors supporting seven different management actions. There was stronger support from dark sky dependent visitors for some elements of alternative lighting practices, but there was still strong support for those who do not participate in dark sky dependent outdoor recreation. Additionally, between 57% and 75% of visitors were interested in learning more about topics related to night skies. This research indicates most visitors would welcome actions to preserve the quality of the rapidly dwindling naturally dark experiences offered by parks and protected areas.

Risk of Infection Following Gunshot Wound Fractures to the Foot and Ankle: A Multicenter Retrospective Study.

The purpose of this multicenter retrospective chart review was to describe demographics, fracture and wound characteristics, and treatments for foot and/or ankle fractures caused by gunshot wounds (GSWs) and identify factors that increase risk of infection in adults treated at 5 urban level 1 trauma centers in South and Midwest regions of the United States. A total of 244 patients sustained GSW-related fractures of the foot/ankle during 2007-2017, of whom 179 had ≥30 days of follow-up data after the initial injury. Most patients were male (95.1%; 232/244) with an average age of 31.2 years. On average, patients sustained 1.3 GSWs (range 1-5) to the foot/ankle. Most GSWs were categorized as low energy (85.1%; 171/201) and the majority (58.2%; 142/244) had retained bullet fragments. Antibiotics were administered at initial presentation to 78.7% (192/244) of patients and 41.8% (102/244) were managed operatively at the time of initial injury. Nerve injury, vascular injury, and infection were documented in, respectively, 8.6% (21/243), 6.6% (16/243), and 17.2% (42/244) of all cases. Multivariable analysis revealed that high-energy injuries and retained bullet fragments increased the risk of infection by 3-fold (odds ratio 3.09, 95% confidence interval 1.16-8.27, p = .025) and 3.5-fold (OR 3.48, 95% CI1.40-8.67; p = .008), respectively. Side of injury, primary injury region, and vascular injury were not significant predictors of infection risk. Further research should examine whether retained bullet fragments are directly associated with infection risk and support the development of guidelines regarding the management of patients with GSW-related fractures to the ankle/foot.

Diverse processing underlying frequency integration in midbrain neurons of barn owls.

Emergent response properties of sensory neurons depend on circuit connectivity and somatodendritic processing. Neurons of the barn owl's external nucleus of the inferior colliculus (ICx) display emergence of spatial selectivity. These neurons use interaural time difference (ITD) as a cue for the horizontal direction of sound sources. ITD is detected by upstream brainstem neurons with narrow frequency tuning, resulting in spatially ambiguous responses. This spatial ambiguity is resolved by ICx neurons integrating inputs over frequency, a relevant processing in sound localization across species. Previous models have predicted that ICx neurons function as point neurons that linearly integrate inputs across frequency. However, the complex dendritic trees and spines of ICx neurons raises the question of whether this prediction is accurate. Data from in vivo intracellular recordings of ICx neurons were used to address this question. Results revealed diverse frequency integration properties, where some ICx neurons showed responses consistent with the point neuron hypothesis and others with nonlinear dendritic integration. Modeling showed that varied connectivity patterns and forms of dendritic processing may underlie observed ICx neurons' frequency integration processing. These results corroborate the ability of neurons with complex dendritic trees to implement diverse linear and nonlinear integration of synaptic inputs, of relevance for adaptive coding and learning, and supporting a fundamental mechanism in sound localization.

Lifetime stress exposure, cognition, and psychiatric wellbeing in women.

Objectives:Although life stress has been associated with worse cognitive and psychiatric functioning, few studies on this topic have examined these associations in older adults and no studies to date have assessed lifetime stress exposure in this context.Method:To address this important issue, we investigated associations between lifetime stress exposure, cognition, and psychiatric wellbeing in 44 women aged 60 and older who completed a comprehensive lifetime stress exposure inventory, two memory tasks, and a complete psychiatric assessment.Results:As hypothesized, greater acute and chronic lifetime stress exposure were both related to poorer psychiatric functioning and more somatic health complaints. Greater lifetime stress exposure was also associated with poorer subjective cognition as indicated by memory and thought problems but not objective indices of memory function.Conclusion:Screening for high life stress exposure may therefore help identify older women at increased risk of experiencing negative psychiatric and cognitive outcomes.

Augmentation of Fracture Repair: Is Anything Ready for Prime Time?

There continues to be a significant burden of disease associated with the delayed healing of common fractures. Despite a number of trials focused on the augmentation of fracture repair, management remains controversial and evidence regarding cost-effectiveness is lacking. The recent evidence that has challenged traditional thinking regarding management of fracture healing problems will be evaluated.

Measurement System for the Environmental Load Assessment of the Scale Ship Model.

The forces and moments acting on a marine vessel caused by the wind are most often modeled based on its speed measured at a standard 10 m above the sea level. There exist numerous well-known methods for modeling wind speed in such conditions. These models, by nature, are inadequate for simulating wind disturbances for free-running scale ship models sailing on lakes. Such scale models are being used increasingly for design and testing modern ship motion control systems. The paper describes the hardware and methodology used in measuring wind speed at low altitudes above the lake level. The system consists of two ultrasonic anemometers supplemented with wave sensor acting as a capacitor immersed partially in the water. Obtained measurement results show clear similarity to the values gathered during full-scale experiments. Analysis of the power spectral density functions of turbulence measured for different mean wind speeds over the lake, indicates that, at the present stage of research, the best model of wind turbulence at low altitude above the lake level can be obtained by assembling four of the known, standard turbulence models.

Helicobacter pylori infection causes both protective and deleterious effects in human health and disease.

Infection with Helicobacter pylori (H. pylori) is necessary but not sufficient for the development of gastric cancer, the third leading cause of cancer death globally. H. pylori infection affects over half of people globally; however, it does not affect populations uniformly. H. pylori infection rates are declining in western industrialized countries but are plateauing in developing and newly industrialized countries where gastric cancer is most prevalent. Despite H. pylori infection being the primary causative agent for gastric cancer, H. pylori infection can also cause other effects, detrimental or beneficial, throughout an individual's life, with the beneficial effects often being seen in childhood and the deleterious effects in adulthood. H. pylori is an ancient bacterium and its likelihood of affecting disease or health is dependent on both human and bacterial genetics that have co-evolved over millennia. In this review, we focus on the impact of infection and its genetic bases in different populations and diseases throughout an individual's lifespan, highlighting the benefits of individualized treatment and argue that universal eradication of H. pylori in its host may cause more harm than good for those infected with H. pylori.

Hybrid Automata Library: A flexible platform for hybrid modeling with real-time visualization.

The Hybrid Automata Library (HAL) is a Java Library developed for use in mathematical oncology modeling. It is made of simple, efficient, generic components that can be used to model complex spatial systems. HAL's components can broadly be classified into: on- and off-lattice agent containers, finite difference diffusion fields, a GUI building system, and additional tools and utilities for computation and data collection. These components are designed to operate independently and are standardized to make them easy to interface with one another. As a demonstration of how modeling can be simplified using our approach, we have included a complete example of a hybrid model (a spatial model with interacting agent-based and PDE components). HAL is a useful asset for researchers who wish to build performant 1D, 2D and 3D hybrid models in Java, while not starting entirely from scratch. It is available on GitHub at https://github.com/MathOnco/HAL under the MIT License. HAL requires the Java JDK version 1.8 or later to compile and run the source code.

Antigen receptor therapy in bone metastasis via optimal control for different human life stages.

In this work we propose a bone metastasis model using power law growth functions in order to describe the biochemical interactions between bone cells and cancer cells. Experimental studies indicate that bone remodeling cycles are different for human life stages: childhood, young adulthood, and adulthood. In order to include such differences in our study, we estimate the model parameter values for each human life stage via bifurcation analysis. Results reveal an intrinsic relationship between the active period of remodeling cycles and the proliferation of cancer cells. Subsequently, using optimal control theory we analyze a possible antigen receptor therapy as a new treatment for bone metastasis. Theoretical results such as existence of optimal solutions are proved. Numerical simulations for late stages of bone metastasis are presented and a discussion of our results is carried out.

Towards the Autonomy: Control Systems for the Ship in Confined and Open Waters.

The concept of the Marine Autonomous Surface Ship (MASS) requires new solutions in many areas: from law, through economics, social sciences, environmental issues to the technology and even ethics. It also plays a central role in the work of numerous research teams dealing with the ship motion control systems. This article presents the results of the experiments with application of the selected control methods in automatic steering of the movement of an autonomous ship in the two regimes: during the maneuvers at low speed (in a harbor confined waters) and during the lake trials in open water conditions. In the first case, multidimensional state controller synthesized with Linear Matrix Inequalities (LMI) algorithms was used, while, in the second case, Model Predictive Control (MPC) control was adopted. The object for which the experiments were carried out was 1:24 scale model of the Liquefied Natural Gas (LNG) carrier. The paper presents also the design of the measurement and control system and the user interface. The experiments were conducted in the natural conditions on the lake. The results of the experiments indicate the fundamental role of the measurement system in the process of controlling an autonomous ship.

Association of preeclampsia with infant APOL1 genotype in African Americans.

BACKGROUND: Black women in the United States and Africa are at an increased risk for preeclampsia. Allelic variants in the gene for apolipoprotein LI, APOL1, are found only in populations of African ancestry, and have been shown to contribute significant risk for kidney disease. Recent studies suggest these APOL1 variants also may contribute risk for preeclampsia. METHODS: The association of preeclampsia with carriage of APOL1 risk alleles was evaluated in a case-control study of deliveries from black women at a single center in Cleveland, Ohio that included gross and histopathologic evaluations of placental tissues (395 cases and 282 controls). Using logistic regression models, associations between fetal APOL1 genotype and preeclampsia were evaluated using several case definitions based on prematurity and severity of preeclampsia, with uncomplicated term pregnancies as controls. Associations between APOL1 genotype and pathological features were also examined. RESULTS: The infant APOL1 genotype was significantly associated with preeclampsia in a dominant inheritance pattern with odds ratio of 1.41 (P=0.029, 95% CI 1.037, 1.926). Stratifying preeclampsia cases by preterm birth, significant associations were detected for both recessive (O.R.=1.70, P=0.038) and additive (O.R.=1.33, P=0.028) inheritance patterns. APOL1 genotype, however, was not significantly associated with pathological changes or other perinatal observations. CONCLUSIONS: Preeclampsia appears to be another disease associated with APOL1 variants, however, further studies are needed to increase confidence in the mode of inheritance. By understanding the association of APOL1 variants with preeclampsia, genetic screening tests for APOL1 may be useful to predict at-risk pregnancies and targeted interventions may be developed to improve pregnancy outcomes.

What Is the Storage Effect, Why Should It Occur in Cancers, and How Can It Inform Cancer Therapy?

Intratumor heterogeneity is a feature of cancer that is associated with progression, treatment resistance, and recurrence. However, the mechanisms that allow diverse cancer cell lineages to coexist remain poorly understood. The storage effect is a coexistence mechanism that has been proposed to explain the diversity of a variety of ecological communities, including coral reef fish, plankton, and desert annual plants. Three ingredients are required for there to be a storage effect: (1) temporal variability in the environment, (2) buffered population growth, and (3) species-specific environmental responses. In this article, we argue that these conditions are observed in cancers and that it is likely that the storage effect contributes to intratumor diversity. Data that show the temporal variation within the tumor microenvironment are needed to quantify how cancer cells respond to fluctuations in the tumor microenvironment and what impact this has on interactions among cancer cell types. The presence of a storage effect within a patient's tumors could have a substantial impact on how we understand and treat cancer.