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Biological systems can rely on collective formation of a metachronal wave in an ensemble of oscillators for locomotion and for fluid transport. We consider one-dimensional chains of phase oscillators with nearest neighbor interactions, connected in a loop and with rotational symmetry, so each oscillator resembles every other oscillator in the chain. Numerical integrations of the discrete phase oscillator systems and a continuum approximation show that directional models (those that do not obey reversal symmetry), can exhibit instability to short wavelength perturbations but only in regions where the slope in phase has a particular sign. This causes short wavelength perturbations to develop that can vary the winding number that describes the sum of phase differences across the loop and the resulting metachronal wave speed. Numerical integrations of stochastic directional phase oscillator models show that even a weak level of noise can seed instabilities that resolve into metachronal wave states.

A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and in human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and on separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.

Background. Asymptomatic childhood cancer survivors (CCS) frequently show decreased exercise performance. Poor exercise performance may indicate impaired future cardiovascular health. Methods. Cardiopulmonary exercise testing (CPET) was performed in asymptomatic off-treatment CCS (age ≥10 years). Those excluded were children with body mass index (BMI) ≥ 30. Patients were divided into Good and Poor performance groups by their peak oxygen consumption (pVO2*) at 35 and 25 ml/kg/min in males and females, respectively. * denotes weight-indexed values. Results. Thirty-eight males (19 Good, 19 Poor) and 41 females (25 Good, 16 Poor) were studied. Total anthracycline dosage was comparable among 4 groups. The BMI, although normal, was significantly higher in Poor groups. Peak work rate (pWR*), pVO2*, peak oxygen pulse (pOP*), and ventilatory anaerobic threshold (VAT*) were significantly lower, whereas heart rate (HR) increase by WR* (DHR/DWR*) and peak respiratory exchange ratio (pRER) was significantly higher in Poor groups. Simultaneously plotting of weight & pVO2 and DHR/DWR* & pOP* revealed a distinct difference between the Good and Poor groups in both sexes, suggesting decreased skeletal muscle mass and decreased stroke volume reserve, respectively, in Poor CCS. Decreased endurance at peak exercise was noted in Poor groups by simultaneously plotting DVO2*/DHR and pOP*. Ventilatory efficiency was mildly diminished in the Poor groups. Conclusions. Decreased stroke volume reserve, decreased skeletal muscle mass, impaired muscle energy metabolism, decreased ventilatory efficiency, and increased BMI characterized Poor CCS in both sexes. This unique combined CPET analysis provides useful clinical biomarkers to screen subclinical cardiovascular abnormality in CCS.

It is important to achieve good persistence and adherence to disease-modifying therapies (DMTs) to achieve the best outcomes in chronic diseases such as multiple sclerosis (MS). The BETACONNECT device is an electronic auto-injector for the DMT interferon beta-1b (Betaseron), designed to improve patients' injection experience and to monitor adherence. This observational study aimed to assess patient adherence to and persistence with interferon beta-1b therapy as well as patient-reported satisfaction in a US population.A prospective, observational, multicenter study was conducted in 146 adult patients with relapsing-remitting MS or clinically isolated syndrome, newly prescribed or currently established on interferon beta-1b therapy and naïve to the BETACONNECT device, and followed up during a 6-month observation period.Among the 91 patients who completed the study, the overall mean adherence rate was 82.5%, with 65.9% of patients adherent for at least 80% for the duration of the 6-month period. At 6 months, 98.9% of patients had less than a 60-day gap in therapy. Of the 115 patients who provided satisfaction data, 90.5% of patients were either very satisfied or satisfied with the BETACONNECT device.This study shows that the BETACONNECT device was associated with high adherence to interferon beta-1b therapy in patients with MS. Patients also reported high degrees of satisfaction with the device. Therefore, this may be a viable delivery option to help with adherence and persistence, potentially leading to improved clinical outcomes.

There is a recent surge of interest in the behavior of active particles that can at the same time align their direction of movement and synchronize their oscillations, known as swarmalators. While theoretical and numerical models of such systems are now abundant, no real-life examples have been shown to date. We present an experimental investigation of the collective motion of the nematode Turbatrix aceti that self-propel by body undulation. We discover that these nematodes can synchronize their body oscillations, forming striking traveling metachronal waves, which produces strong fluid flows. We uncover that the location and strength of this collective state can be controlled through the shape of the confining structure; in our case the contact angle of a droplet. This opens a way for producing controlled work such as on-demand flows or displacement of objects. We illustrate this by showing that the force generated by this state is sufficient to change the physics of evaporation of fluid droplets, by counteracting the surface-tension force, which allow us to estimate its strength. The relatively large size and ease of culture make Turbatrix aceti a promising model organism for experimental investigation of swarming and oscillating active matter capable of producing controllable work.

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and circulate in the blood, making them attractive biomarkers of disease state for tissues like bone that are challenging to interrogate directly. Here, we report on five miRNAs-miR-197-3p, miR-320a, miR-320b, miR-331-5p, and miR-423-5p-associated with bone mineral density (BMD) in 147 healthy adult baboons. These baboons ranged in age from 15 to 25 years (45-75 human equivalent years) and 65% were female with a broad range of BMD values including a minority of osteopenic animals. miRNAs were generated via RNA sequencing from buffy coats collected at necropsy and areal BMD (aBMD) measured postmortem via dual-energy X-ray absorptiometry (DXA) of the lumbar vertebrae. Differential expression analysis controlled for the underlying pedigree structure of these animals to account for genetic variation which may drive miRNA abundance and aBMD values. While many of these miRNAs have been associated with the risk of osteoporosis in humans, this finding is of interest because the cohort represents a model of normal aging and bone metabolism rather than a disease cohort. The replication of miRNA associations with osteoporosis or other bone metabolic disorders in animals with healthy aBMD suggests an overlap in normal variation and disease states. We suggest that these miRNAs are involved in the regulation of cellular proliferation, apoptosis, and protein composition in the extracellular matrix throughout life; and age-related dysregulation of these systems may lead to disease. These miRNAs may be early indicators of progression to disease in advance of clinically detectible osteoporosis.

Retinal ganglion cell (RGC) death causes irreversible vision loss in patients with glaucoma and other forms of optic neuropathy because the mammalian retina and optic nerve lack endogenous regenerative capacity. RGC transplantation and optic nerve regeneration represent a potential translational approach to vision restoration in glaucoma secondary to RGC loss. Functional RGC replacement requires that 1) donor RGCs integrate into the recipient retina and receive synaptic input from afferent bipolar and amacrine cells and that 2) donor RGCs extend their axons and establish synaptic connections to appropriate neurons in the brain. Here, in an effort to address retinal integration, we demonstrate that the internal limiting membrane (ILM) acts as a physical barrier to the integration of transplanted human stem cell-derived RGCs (hRGCs) into the recipient retina following intravitreal transplantationin vivo. To circumvent the ILM barrier, we intravitreally injected the nonspecific protease pronase-E in immunosuppressed adult C57BL/6J mice prior to transplantation of hRGCs. Separately, we also transplanted hRGCs into adultLama1nmf223mice, which harbor a point mutation in theirLama-α1gene that causes developmental ILM dysgenesis. We assessed donor hRGC survival and engraftment using 3D reconstructions of confocal z-stacks in retinal flatmounts. Migration of surviving donor RGC somas into the recipient RGC layer significantly increased after proteolytic or developmental ILM disruption. Moreover, lamination of dendritic arbors into the recipient inner plexiform layer was observed exclusively following ILM disruption. To assess the clinical translatability of this finding, we transplanted hRGCs onto postmortem organotypic human retinal explant cultures and observed significantly increased engraftment following proteolytic ILM digestion. These findings enhance our understanding of the barriers faced by transplanted hRGCs in the adult murine and human retina and provide an avenue for clinically translatable regenerative medicine approaches to vision restoration in optic neuropathy.

Patients with advanced cancer and minor children experience high rates of depression and anxiety. However, associations between parental status and other aspects of the patient experience are not well understood. This study compared patient-reported outcomes of patients with and without minor children.This was a retrospective analysis of 448 adults with stage III or IV solid tumors from a public research registry.Multiple linear regression models or modified Poisson regression models were fitted to evaluate differences in health-related quality of life, global health, and patient satisfaction scores between patients living with and without minors.One in five patients lived with minor children. They reported significantly worse health-related quality of life, global physical health, and global mental health. They also expressed lower satisfaction with time spent with their provider, communication, and financial aspects.Patients with minor children may benefit from earlier identification and support for their psychosocial needs and concerns.

To identify changes in response to experimental intraocular pressure (IOP) elevation associated with the laminin α1 nmf223 mutation in mice. Laminin mutant (LM) mice (Lama1(nmf223)) and C57BL/6J (B6) mice in two age groups each (4-5 months and >1 year) underwent intracameral microbead injections to produce unilaterally elevated IOP. We assessed axonal transport block of immunofluorescently labeled amyloid precursor protein (APP) after 3 days and retinal ganglion cell (RGC) axon loss after 6 weeks. Light, electron and fluorescent microscopy was used to study baseline anatomic differences and effects of 3-day IOP elevation in younger LM mice. In younger mice of both LM and B6 strains, elevated IOP led to increased APP block in the retina, prelaminar optic nerve head (preONH), unmyelinated optic nerve (UON), and myelinated optic nerve (MON). APP blockade not significantly different between younger B6 and LM mouse strains. Older LM mice had greater APP accumulation in both control and glaucoma eyes compared to older B6, however, accumulation was not significantly greater in LM glaucoma eyes compared to LM controls. Axon loss at 6 weeks was 12.2% in younger LM and 18.7% in younger B6 mice (difference between strains, p = 0.22, Mann Whitney test). Untreated LM optic nerve area was lower compared to B6 (nerve area, p < 0.0001, t-test). Aberrant axon bundles, as well as defects, thickening and reduplication of pia mater, were seen in the optic nerves of younger LM mice. Axonal transport blockade significantly differed between old B6 and old LM mice in control and glaucoma eyes, and younger LM mice had abnormal axon paths and lower optic nerve area.

We show that Smoothed Particle Hydrodynamics (SPH) simulations of dwarf galaxies interacting with a Milky Way-like disk produce moving groups in the simulated stellar disk. We analyze three different simulations: one that includes dwarf galaxies that mimic the Large Magellanic Cloud, Small Magellanic Cloud and the Sagittarius dwarf spheroidal; another with a dwarf galaxy that orbits nearly in the plane of the Milky Way disk; and a null case that does not include a dwarf galaxy interaction. We present a new algorithm to find large moving groups in the $V_R, V_\phi$ plane in an automated fashion that allows us to compare velocity sub-structure in different simulations, at different locations, and at different times. We find that there are significantly more moving groups formed in the interacting simulations than in the isolated simulation. A number of dwarf galaxies are known to orbit the Milky Way, with at least one known to have had a close pericenter approach. Our analysis of simulations here indicates that dwarf galaxies like those orbiting our Galaxy produce large moving groups in the disk. Our analysis also suggests that some of the moving groups in the Milky Way may have formed due to dynamical interactions with perturbing dwarf satellites. The groups identified in the simulations by our algorithm have similar properties to those found in the Milky Way, including similar fractions of the total stellar population included in the groups, as well as similar average velocities and velocity dispersions., Comment: 15 pages, 12 figures, Accepted for publication in MNRAS. Major revisions in the accepted version of the paper

The article provides a guide to use the headphones and virtual reality headsets to locate and dislocate theatre audience, in times of social proximity as well as social distance. It mentions about the popularity of the Zoom chat window and the exuberance with which audience members sometimes participate in the discussion that is simultaneous with a live performance.

Background and Aims: Worldwide, the incidence of COVID-19 is lower in children than in adults and symptoms are less severe. So far, few studies from Latin America have been published on the behavior of COVID-19 in children with cancer. Purpose: To characterize the epidemiology, clinical course, morbidity, and mortality in children with cancer and COVID-19. Methods: All patients registered in the Argentine National Pediatric Cancer Registry (ROHA) with diagnosis of SARS-CoV-2 between December 4, 2020, and May 3, 2022 were included. Variables analyzed were: sex, age at COVID-19 diagnosis, clinical presentation at diagnosis, symptom severity, tumor type, intensive care requirement, specific treatment for COVID-19, vital status, and cause of death. Mortality was analyzed comparing the three main waves. Results: Overall, 888 children with cancer and COVID-19 infection were registered (484 females); 437 (49.2%) had leukemia, followed by central nervous system tumors (CNS-T) 120 (13.5%). Of the children, 57.2% (n=508) were symptomatic; 75% were febrile, and 37% (n=210) had neutropenia; 17.1% (n=152) were diagnosed within one month of cancer diagnosis. A total of 154 children had severe or critical symptoms (17%). In this study, 112 deaths were reported, 105 (94%) due to disease progression, sepsis, comorbidities, or treatment complications. Seven patients (0.8%) died from COVID-19, all diagnosed with leukemia/lymphoma. No association of deaths was found between the three waves analyzed. Conclusions: Based on the ROHA data, we may conclude that in pediatric cancer patients, contrary to what was initially expected, morbidity and mortality due to COVID-19 were not increased.

Objective This study was conducted to understand the impact of tracking migraine via an app on patient-provider communication and migraine outcomes as well as patient perspectives of the app. Methods Data collected were (1) patient-reported via a smartphone app developed for tracking migraines and (2) provided by integrated delivery networks. Results Results contribute to the understanding that migraines place substantial physical and functional burden on people and highlight the role that tracking symptoms may play to improve migraine management. Conclusions Digital tools, such as apps, aid in communication between patients and health care providers, possibly enhancing patient knowledge and understanding of their migraines and health care providers being able to better treat patients.

OBJECTIVE To assess the real-world efficacy, tolerability, and safety of ubrogepant in a tertiary headache center. BACKGROUND The efficacy and safety of ubrogepant for the acute treatment of migraine were established in phase 3 randomized controlled trials. However, there is no real-world data of patient experience with ubrogepant in a population in which the majority of patients have chronic migraine, multiple prior unsuccessful treatments, complex medical comorbidities, and concurrent use of other migraine-specific medications. METHOD This was a post-market cohort study conducted at Mayo Clinic Arizona. All patients prescribed ubrogepant were tracked and contacted 1-3 months after the prescription to answer a list of standardized questions. Demographic information and additional headache history were obtained from chart review. RESULTS We obtained eligible questionnaire responses from 106 patients. Chronic migraine accounted for 92/106 (86.8%) of the population. Complete headache freedom (from mild/moderate/severe to no pain) and headache relief (from moderate/severe to mild/no pain or mild to no pain) for ≥75% of all treated attacks at 2 hours after taking ubrogepant were achieved in 20/105 (19.0%) and 50/105 (47.6%) patients, respectively. A total of 33/106 (31.1%) patients reported being "very satisfied" with ubrogepant. Adverse events were reported in 42/106 (39.6%) patients, including fatigue in 29/106 (27.4%), dry mouth in 8/106 (7.5%), nausea/vomiting in 7/106 (6.6%), constipation in 5/106 (4.7%), dizziness in 3/106 (2.8%), and other adverse events in 7/106 (6.6%). Predictive factors for being a "good responder" to ubrogepant, defined as headache relief for ≥75% of all treated attacks at 2 hours after taking ubrogepant, included migraine with aura, episodic migraine

The Apollo lunar samples reveal that Earth and the Moon have strikingly similar isotopic ratios, suggesting that these bodies may share the same source materials. This leads to the "standard" giant impact hypothesis, suggesting the Moon formed from a partially vaporized disk that was generated by an impact between the proto-Earth and a Mars-sized impactor. This disk would have had high temperature (~ 4000 K) and vapor mass fraction of ~20 wt %. However, impact simulations indicate that this model does not mix the two bodies well, making it challenging to explain the isotopic similarity. In contrast, more energetic impacts, such as a collision between two half Earth-sized objects, could mix the two bodies well, naturally solving the problem. These impacts would produce much higher disk temperatures (6000-7000K) and higher vapor mass fractions (~80-90 wt%). These energetic models, however, may have a challenge during the Moon accretion phase. Our analyses suggest that km-sized moonlets, which are building blocks of the Moon, would experience strong gas drag from the vapor portion of the disk and fall onto Earth on a very short timescale. This problem could be avoided if large moonlets (>1000 km) form very quickly by the process called streaming instability, which is a large clump formation mechanism due to spontaneous concentration of dust particles followed by gravitational collapse. We investigate this possibility by conducting numerical simulations with the code called Athena. Our 2D and 3D hydrodynamic simulations show that moonlet formation by streaming instability is possible in the Moon-forming disk, but their maximum size is approximately 50 km, which is not large enough to avoid the strong gas drag. This result supports the Moon formation models that produce vapor-poor disks, such as the standard model. We will further discuss implications for moons in the solar system and extrasolar systems (exomoons).

Background Late-onset cardiovascular complications are of serious concerns for even asymptomatic pediatric cancer survivors (PCS). We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. Methods We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. Results Fifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were significantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46 watt, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ΔHR/ΔWR) and lower peak oxygen pulse (OP) at the peak exercise. Twelve PCS with high peak RQ (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory efficiency (lower DVE/DVCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Conclusions Poor exercise performance in PCS is mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multi-factorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS. (244 words)

With backwards orbit integration we estimate birth locations of young stellar associations and moving groups identified in the solar neighborhood that are younger than 70 Myr. The birth locations of most of these stellar associations are at smaller galactocentric radius than the Sun, implying that their stars moved radially outwards after birth. Exceptions to this rule include are the Argus and Octans associations which formed outside the Sun's Galactocentric radius. Variations in birth heights of the stellar associations suggest that they were born in a corrugated disk of molecular clouds, similar to that inferred from the current filamentary molecular cloud distribution and dust extinction maps. Multiple spiral arm features with different but near corotation pattern speeds and at different heights could account for the stellar association birth sites. We find that the young stellar associations are located in between peaks in the UV stellar velocity distribution for stars in the solar neighborhood. This would be expected if they were born in a spiral arm which perturbs stellar orbits that cross it. In contrast, stellar associations seem to be located near peaks in the vertical phase space distribution, suggesting that the gas in which stellar associations are born moves vertically together with the low velocity dispersion disk stars., Comment: The animated movie is available here: http://astro.pas.rochester.edu/~aquillen/figures/movie3D.gif

The emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has created an unprecedented healthcare, social, and economic disaster. Wearing of masks and social distancing can significantly decrease transmission and spread, however, due to circumstances such as medical or dental intervention and personal choice these practices have not been universally adopted. Additional strategies are required to lessen transmission. Nasal rinses and mouthwashes, which directly impact the major sites of reception and transmission of human coronaviruses (HCoV), may provide an additional level of protection against the virus. Common over-the-counter nasal rinses and mouthwashes/gargles were tested for their ability to inactivate high concentrations of HCoV using contact times of 30 s, 1 min, and 2 min. Reductions in titers were measured by using the tissue culture infectious dose 50 (TCID50 ) assay. A 1% baby shampoo nasal rinse solution inactivated HCoV greater than 99.9% with a 2-min contact time. Several over-the-counter mouthwash/gargle products including Listerine and Listerine-like products were highly effective at inactivating infectious virus with greater than 99.9% even with a 30-s contact time. In the current manuscript we have demonstrated that several commonly available healthcare products have significant virucidal properties with respect to HCoV.

Background Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports. Materials and Methods Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms. Results In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36–3.45) and anxiety (RR, 1.48; 95% CI, 1.05–2.09). Conclusion Oncologists frequently underestimate patients’ depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms. Implications for Practice In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients’ mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients’ psychological health.

In 1964, the United States Supreme Court affirmed by its decision in Jacobellis vs. Ohio that the French art film, Les Amants, was not, as the State of Ohio had previously defined it, “hardcore pornography.” In his concurrent opinion, Justice Potter Stewart wrote that, though he couldn’t properly define what might constitute “hardcore pornography,” it was something that would be obvious to most of us, especially when compared to a bawdy, yet otherwise harmless, foreign film. His exact words were: “but I know it when I see it.” And while Justice Stewart’s simple acknowledgment that we might “know” what something means merely based on our personal perceptions helped justify the Court’s stance on how it approached similar obscenity laws (as well as made him famous) from that point on, it also serves us well in our own search for definitions of words like “religion” or “Atheism.” This article will use Justice Stewart’s argument as a base of discussion for the latter, providing in the process examples of Atheists across three historical periods, that will in turn support a practical description of the term itself, while simultaneously challenging the need for a “definition of Atheism” in the first place.

There is a recent surge of interest in the behavior of active particles that can at the same time align their direction of movement and synchronize their oscillations, known as

The authors explore the possibility that near-earth, rubble pile asteroids might be used as habitats for human settlement by increasing their rotation to produce spin gravity. Using previously published scaling by Maindl et al. and studies of asteroid populations, it is shown that there is no class of hollowed body that would survive the spin-up process on its own without additional reinforcement. Large solid-rock asteroids (diameter D > 10 km) would not have the tensile strength to withstand the required rotation rates and would fracture and break apart. Smaller asteroids, being ‘rubble piles’, have little tensile strength and would quickly disperse. The possibility of containing the asteroid mass using higher-strength materials like carbon nanofiber is instead considered. It is found that a moderate tensile strength container can maintain the integrity of a large spinning cylinder composed of dispersed asteroid regolith. The research extends the range of possible asteroid habitat candidates, since it may become feasible to construct habitats from the more numerous smaller bodies, including NEAs (Near Earth Asteroids). The required tensile strength of the container material scales with habitat radius and thickness and is ∼ 200 MPa for a starting asteroid body of radius 300 m that is spun up to provide 0.3 g⊕ while increasing its radius to 3 km and maintaining a rubble and regolith shield thickness of 2 m to protect against cosmic rays. Ambient solar power can be harvested to aid in spin-up and material processing.

Recent experiments have shown that the nematode {\it T. aceti} can assemble into collectively undulating groups at the edge of fluid drops. This coordinated state consists of metachronal waves and drives fluid circulation inside the drop. We find that the circulation velocity is about 2 mm/s and nearly half the speed of the metachronal wave. We develop a quasi two-dimensional hydrodynamics model using the Stokes flow approximation. The periodic motion of the nematodes constitute our moving boundary condition that drives the flow. Our model suggests that large amplitude excursions of the nematodes tails produce the fluid circulation. We discuss the constraints on containers that would enhance fluid motion, which could be used in the future design of on demand flow generating systems.

Nonhuman primates (NHPs) are a critical component of translational/preclinical biomedical research due to the strong similarities between NHP and human physiology and disease pathology. In some cases, NHPs represent the most appropriate, or even the only, animal model for complex metabolic, neurological, and infectious diseases. The increased demand for and limited availability of these valuable research subjects requires that rigor and reproducibility be a prime consideration to ensure the maximal utility of this scarce resource. Here, we discuss a number of approaches that collectively can contribute to enhanced rigor and reproducibility in NHP research.

Aquaporin 4 is absent from astrocytes in the rodent optic nerve head, despite high expression in the retina and myelinated optic nerve. The purpose of this study was to quantify regional aquaporin channel expression in astrocytes of the porcine and human mouse optic nerve (ON). Ocular tissue sections were immunolabeled for aquaporins 1(AQP1), 4(AQP4), and 9(AQP9), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP) and alpha-dystroglycan (αDG) for their presence in retina, lamina, myelin transition zone (MTZ, region just posterior to lamina) and myelinated ON (MON). Semi- quantification of AQP4 labeling & real-time quantitative PCR (qPCR) data were analyzed in retina and ON tissue. Porcine and control human eyes had abundant AQP4 in Müller cells, retinal astrocytes, and myelinated ON (MON), but minimal expression in the lamina cribrosa. AQP1 and AQP9 were present in retina, but not in the lamina. Immunolabeling of GFAP and αDG was similar in lamina, myelin transition zone (MTZ) and MON regions. Semi-quantitative AQP4 labeling was at background level in lamina, increasing in the MTZ, and highest in the MON (lamina vs MTZ, MON; p≤0.05, p≤0.01, respectively). Expression of AQP4 mRNA was minimal in lamina and substantial in MTZ and MON, while GFAP mRNA expression was uniform among the lamina, MTZ, and MON regions. Western blot assay showed AQP4 protein expression in the MON samples, but none was detected in the lamina tissue. The minimal presence of AQP4 in the lamina is a specific regional phenotype of astrocytes in the mammalian optic nerve head.

Resilience to stressors is a major component of biological aging and may mediate the onset of multimorbidity in older adults. The Wake Forest Non-Human Primate Radiation Survivor Cohort (RSC) provides a novel opportunity to study aging and resilience in 250 rhesus macaques (Macaca mulatta) with single-dose radiation exposures 0–15 years prior and 50 controls with semi-annual clinical, imaging, and biomarker measurements taken over their lifespan. Multimorbidity is extremely common among irradiated animals. Only 38% of animals have none of 20 common chronic diseases, falling to 16% of animals over age 8 and 11% over age 10 (middle-aged animals). 70% of animals have 5 or more diagnoses in this oldest cohort. The presence of any one disease increases the likelihood of having a second, co-morbid condition. Nevertheless, some animals continue disease-free until late in life, highlighting substantial variability in resilience. To identify patterns of multimorbidity, survival curves for each diagnosis were generated for age and time since radiation and k-median clustered resulting in four groupings of aging-associated morbidities. Bone, brain, and gastrointestinal disorders arise 3.5 years after radiation on average, followed by skin, heart, and cataracts. At 4.65 years, animals are at increased risk of being underweight and overweight and developing diabetes, hypertension, and hepatic dysfunction. Tumor, lung, and kidney disorders arise approximately 6 years after exposure. In all cases, these age-related disorders occur significantly earlier in irradiated animals than controls. These findings highlight the clustering of multimorbidities in aging, radiation-challenged primates and the potential of the RSC in studying resilience.

Individual variation in the age of pubertal onset is linked to physical and mental health, yet the factors underlying this variation are poorly understood. Life history theory predicts that individuals at higher risk of mortality due to extrinsic causes such as infectious disease should sexually mature and reproduce earlier, whereas those at lower risk can delay puberty and continue to invest resources in somatic growth. We examined relationships between a genetic predictor of infectious disease resistance, heterozygosity of the major histocompatibility complex (MHC), referred to as the human leukocyte antigen (HLA) gene in humans, and self-reported pubertal timing. In a combined sample of men from Canada (n = 137) and the United States (n = 43), MHC heterozygosity predicted later self-reported pubertal development. These findings suggest a genetic trade-off between immunocompetence and sexual maturation in human males.

In this study, we investigated how the brain responds to task difficulty in linguistic and non-linguistic contexts. This is important for the interpretation of functional imaging studies of neuroplasticity in post-stroke aphasia, because of the inherent difficulty of matching or controlling task difficulty in studies with neurological populations. Twenty neurologically normal individuals were scanned with fMRI as they performed a linguistic task and a non-linguistic task, each of which had two levels of difficulty. Critically, the tasks were matched across domains (linguistic, non-linguistic) for accuracy and reaction time, such that the differences between the easy and difficult conditions were equivalent across domains. We found that non-linguistic demand modulated the same set of multiple demand (MD) regions that have been identified in many prior studies. In contrast, linguistic demand modulated MD regions to a much lesser extent, especially nodes belonging to the dorsal attention network. Linguistic demand modulated a subset of language regions, with the left inferior frontal gyrus most strongly modulated. The right hemisphere region homotopic to Broca’s area was also modulated by linguistic but not non-linguistic demand. When linguistic demand was mapped relative to non-linguistic demand, we also observed domain by difficulty interactions in temporal language regions as well as a widespread bilateral semantic network. In sum, linguistic and non-linguistic demand have strikingly different neural correlates. These findings can be used to better interpret studies of patients recovering from aphasia. Some reported activations in these studies may reflect task performance differences, while others can be more confidently attributed to neuroplasticity.

Nonhuman primates (NHPs) are a critical component of translational/preclinical biomedical research due to the strong similarities between NHP and human physiology and disease pathology. In some cases, NHPs represent the most appropriate, or even the only, animal model for complex metabolic, neurological, and infectious diseases. The increased demand for and limited availability of these valuable research subjects requires that rigor and reproducibility be a prime consideration to ensure the maximal utility of this scarce resource. Here, we discuss a number of approaches that collectively can contribute to enhanced rigor and reproducibility in NHP research.

BackgroundDietary high fructose (HFr) is a known metabolic disruptor contributing to development of obesity and diabetes in Western societies. Initial molecular changes from exposure to HFr on liver metabolism may be essential to understand the perturbations leading to insulin resistance and abnormalities in lipid and carbohydrate metabolism. We studied vervet monkeys (Clorocebus aethiops sabaeus) fed a HFr (n=5) or chow diet (n=5) for 6 weeks, and obtained clinical measures of liver function, blood insulin, cholesterol and triglycerides. In addition, we performed untargeted global transcriptomics, proteomics, and metabolomics analyses on liver biopsies to determine the molecular impact of a HFr diet on coordinated pathways and networks that differed by diet.ResultsWe show that integration of omics data sets improved statistical significance for some pathways and networks, and decreased significance for others, suggesting that multiple omics datasets enhance confidence in relevant pathway and network identification. Specifically, we found that sirtuin signaling and a peroxisome proliferator activated receptor alpha (PPARA) regulatory network were significantly altered in hepatic response to HFr. Integration of metabolomics and miRNAs data further strengthened our findings.ConclusionsOur integrated analysis of three types of omics data with pathway and regulatory network analysis demonstrates the usefulness of this approach for discovery of molecular networks central to a biological response. In addition, metabolites aspartic acid and docosahexaenoic acid (DHA), protein ATG3, and genesATG7, HMGCS2link sirtuin signaling and the PPARA network suggesting molecular mechanisms for altered hepatic gluconeogenesis from consumption of a HFr diet.

To measure quantitatively changes in lamina cribrosa (LC) cell and connective tissue structure in human glaucoma eyes.We studied 27 glaucoma and 19 age-matched non-glaucoma postmortem eyes. In 25 eyes, LC cross-sections were examined by confocal and multiphoton microscopy to quantify structures identified by anti-glial fibrillary acidic protein (GFAP), phalloidin-labeled F-actin, nuclear 4',6-diamidino-2-phenylindole (DAPI), and by second harmonic generation imaging of LC beams. Additional light and transmission electron microscopy were performed in 21 eyes to confirm features of LC remodeling, including immunolabeling by anti-SOX9 and anti-collagen IV. All glaucoma eyes had detailed clinical histories of open-angle glaucoma status, and degree of axon loss was quantified in retrolaminar optic nerve cross-sections.Within LC pores, the proportionate area of both GFAP and F-actin processes was significantly lower in glaucoma eyes than in controls (P = 0.01). Nuclei were rounder (lower median aspect ratio) in glaucoma specimens (P = 0.02). In models assessing degree of glaucoma damage, F-actin process width was significantly wider in glaucoma eyes with more damage (P = 0.024), average LC beam width decreased with worse glaucoma damage (P = 0.042), and nuclear count per square millimeter rose with worse damage (P = 0.019). The greater cell count in LC pores represented 92.3% astrocytes by SOX9 labeling. The results are consistent with replacement of axons in LC pores by basement membrane labeled by anti-collagen IV and in-migrating astrocytes.Alteration in LC structure in glaucoma involves migration of astrocytes into axonal bundles, change in astrocyte orientation and processes, production of basement membrane material, and thinning of connective tissue beams.

In this paper we use a Soft-Sphere Discrete Element method code to simulate the transmission and study the attenuation of a seismic wave. Then, we apply our findings to the different space missions that have had to touch the surface of different small bodies. Additionally, we do the same in regards to the seismic wave generated by the hypervelocity impacts produced by the DART and Hayabusa2 missions once the shock wave transforms into a seismic wave. We find that even at very low pressures, such as those present in the interior of asteroids, the seismic wave speed can still be on the order of hundreds of m/s depending on the velocity of the impact that produces the wave. As expected from experimental measurements, our results show that wave velocity is directly dependent on $P^{1/6}$, where $P$ is the total pressure (confining pressure plus wave induced pressure). Regardless of the pressure of the system and the velocity of the impact (in the investigated range), energy dissipation is extremely high. These results provide us with a way to anticipate the extent to which a seismic wave could have been capable of moving some small particles on the surface of a small body upon contact with a spacecraft. Additionally, this rapid energy dissipation would imply that even hypervelocity impacts should perturb only the external layer of a self-gravitating aggregate on which segregation and other phenomena could take place. This would in turn produce a layered structure of which some evidence has been observed, Accepted for publication in The Planetary Sciences Journal

Ruxolitinib is a Janus kinase 1/2 inhibitor that blocks signal transduction of interferon-gamma, a critical cytokine involved in the pathogenesis of cutaneous lichen planus (LP). In this prospective phase II study, we investigated the efficacy of topical ruxolitinib in cutaneous LP and performed transcriptomic analysis before and after therapy. Twelve patients with cutaneous LP applied topical ruxolitinib twice daily for 8 weeks. Primary endpoints were changes in total lesion count and changes in modified Composite Assessment of Index Lesion Severity score in index treated and untreated index control lesions at week 4. Total lesion count decreased by a median of 50 lesions (interquartile range 25, 723; P0.001). modified Composite Assessment of Index Lesion Severity scores decreased by a mean difference of 7.6 (standard deviation 8.8, P = 0.016) between index treated and control lesions. Type I and II interferon pathways were enriched in LP, and responsive disease displayed downregulation of interferon-stimulated genes. In this small pilot study, topical ruxolitinib was highly effective in the treatment of cutaneous LP. Transcriptomic analysis confirmed LP as an interferon-driven disease and downregulation of interferon-stimulated genes correlated with disease response.

Objectives Severe COVID-19 results in a glucocorticoid responsive form of acute respiratory distress (ARDS)/diffuse alveolar damage (DAD). Herein we compare the immunopathology of lung tissue procured at autopsy in patients dying of SARS-CoV-2 with those dying of DAD prior to the COVID-19 pandemic. Methods Autopsy gross and microscopic features stratified by duration of illness in twelve patients who tested positive for SARS-CoV-2 viral RNA as well as seven patients dying of DAD prior to the COVID-19 pandemic were evaluated with multiplex (5-plex: CD4, CD8, CD68, CD20, AE1/AE3) and SARS-CoV immunohistochemistry to characterize the immunopathologic stages of DAD. Results We observed a distinctive pseudopalisaded histiocytic hyperplasia interposed between the exudative and proliferative phase of COVID-19 associated DAD which was most pronounced at the fourth week from symptom onset. Pulmonary macrothrombi were seen predominantly in cases with pseudopalisaded histiocytic hyperplasia and/or proliferative phase DAD. Neither pseudopalisaded histiocytic hyperplasia nor pulmonary macrothrombi were seen in non-COVID-19 DAD cases, whereas microthrombi were common in DAD regardless of etiology. Conclusion The inflammatory pattern of pseudopalisaded histiocytic hyperplasia may represent the distinctive immunopathology associated with the dexamethasone responsive form of DAD seen in severe COVID-19.

Using viscoelastic mass spring model simulations to track heat distribution inside a tidally perturbed body, we measure the asymmetry of heating in the crust of a spin synchronous Moon in eccentric orbit about the Earth. With the Moon within a few Earth radii of the Earth, we find that tidal heating per unit area in a lunar crustal shell is asymmetric due to the octupole order moment in the Earth's tidal field and is 10 to 20\% higher on its near side than on its far side. Tidal heating reduces the crustal basal heat flux and the rate of magma ocean crystallization. Assuming that the local crustal growth rate depends on the local basal heat flux and the distribution of tidal heating in latitude and longitude, a heat conductivity model illustrates that a moderately asymmetric and growing lunar crust could maintain its asymmetry. Near/far side asymmetric tidal heating could serve as a trigger for uneven lunar crustal growth., Comment: Accepted Icarus

The purpose of this paper is to present a new path-planning algorithm for planetary exploration rovers that will guide the vehicle safely to a reachable state. In particular, this work will make use of a special class of artificial potential functions called navigation functions which are guaranteed to be free of local minimum. The construction of the navigation functions in this work is motivated by the grid-based wavefront expansion method but differs in that the contour levels are defined in terms of the control effort of the system. Two new methods will be introduced in this paper for defining the navigation function. The first method will generate a minimum control effort path plan and the second method will be based on an inverse dynamics approach. Each of the control effort based methods will generate a path plan that will guide the rover’s approach towards an objective reachable state. Finally, a stable backstepping-like controller is implemented to track a trajectory defined along the path plan to the rover’s objective.