Oligomeric collagen as an encapsulation material for islet/ß-cell replacement: effect of islet source, dose, implant site, and administration format.

Replacement of islets/ß-cells that provide long-lasting glucose-sensing and insulin-releasing functions has the potential to restore extended glycemic control in individuals with type 1 diabetes. Unfortunately, persistent challenges preclude such therapies from widespread clinical use, including cumbersome administration via portal vein infusion, significant loss of functional islet mass upon administration, limited functional longevity, and requirement for systemic immunosuppression. Previously, fibril-forming type I collagen (oligomer) was shown to support subcutaneous injection and in situ encapsulation of syngeneic islets within diabetic mice, with rapid (<24 h) reversal of hyperglycemia and maintenance of euglycemia for beyond 90 days. Here, we further evaluated this macroencapsulation strategy, defining effects of islet source (allogeneic and xenogeneic) and dose (500 and 800 islets), injection microenvironment (subcutaneous and intraperitoneal), and macrocapsule format (injectable and preformed implantable) on islet functional longevity and recipient immune response. We found that xenogeneic rat islets functioned similarly to or better than allogeneic mouse islets, with only modest improvements in longevity noted with dosage. Additionally, subcutaneous injection led to more consistent encapsulation outcomes along with improved islet health and longevity, compared with intraperitoneal administration, whereas no significant differences were observed between subcutaneous injectable and preformed implantable formats. Collectively, these results document the benefits of incorporating natural collagen for islet/ß-cell replacement therapies.

Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

BACKGROUND: Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. METHODS: Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. RESULTS: A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = - 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = - 6.94) compared to the non-TC group (change = - 1.21, p for interaction = 0.07) and healthy controls (change = 0.09, p for interaction = 0.02). CONCLUSIONS: There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group; however, exploratory analyses demonstrated a reduction in both temporal lobe volume and oral reading recognition scores among patients on the TC regimen. These results suggest that different chemotherapy regimens may have differential effects on brain volume and cognition. Future, larger studies focusing on older adults with cancer on different treatment regimens are needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01992432 . Registered on 25 November 2013. Retrospectively registered.

Computational Fluid Dynamics of Vascular Disease in Animal Models.

Recent applications of computational fluid dynamics (CFD) applied to the cardiovascular system have demonstrated its power in investigating the impact of hemodynamics on disease initiation, progression, and treatment outcomes. Flow metrics such as pressure distributions, wall shear stresses (WSS), and blood velocity profiles can be quantified to provide insight into observed pathologies, assist with surgical planning, or even predict disease progression. While numerous studies have performed simulations on clinical human patient data, it often lacks prediagnosis information and can be subject to large intersubject variability, limiting the generalizability of findings. Thus, animal models are often used to identify and manipulate specific factors contributing to vascular disease because they provide a more controlled environment. In this review, we explore the use of CFD in animal models in recent studies to investigate the initiating mechanisms, progression, and intervention effects of various vascular diseases. The first section provides a brief overview of the CFD theory and tools that are commonly used to study blood flow. The following sections are separated by anatomical region, with the abdominal, thoracic, and cerebral areas specifically highlighted. We discuss the associated benefits and obstacles to performing CFD modeling in each location. Finally, we highlight animal CFD studies focusing on common surgical treatments, including arteriovenous fistulas (AVF) and pulmonary artery grafts. The studies included in this review demonstrate the value of combining CFD with animal imaging and should encourage further research to optimize and expand upon these techniques for the study of vascular disease.

Pyocyanin induces systemic oxidative stress, inflammation and behavioral changes in vivo.

Pyocyanin (PCN) is a virulence factor secreted by Pseudomonas aeruginosa (P. aeruginosa) that has been shown to have numerous toxic effects in both in vitro and in vivo studies. Such toxicities include pro-inflammatory and pro-oxidant mediated responses. It is hypothesized that PCN can cross biological membranes and reach the systemic circulation, but no previous studies have investigated this. The aim of this study was, therefore, to quantify PCN in plasma and assess if systemic responses were occurring after localized intranasal administration in C57BL/6 J mice. This was achieved through the plasma quantification of PCN and assessment of changes to behavior using two commonly used tests, the forced swimming test and the open field test. Furthermore, evidence of systemic oxidative stress and inflammation was measured using malondialdehyde (MDA) and TNF-α post PCN exposure. PCN was found to cross into systemic circulation but in a variable manner. Furthermore, significant increases in plasma TNF-α and MDA (both p < 0.001) were observed along with changes in behavior indicative of systemic inflammatory responses.

Synthesis and characterization of polystyrene embolization particles doped with tantalum oxide nanoparticles for X-ray contrast.

Radiopaque and fluorescent embolic particles have been synthesized and characterised to match the size of vasculature found in tumours to ensure effective occlusion of the vessels. A literature search showed that the majority of vessels surrounding a tumour were less than 50 µm and therefore polydispersed polystyrene particles with a peak size of 50 µm have been synthesised. The embolic particles contain 5-8 nm amorphous tantalum oxide nanoparticles which provide X-ray contrast. Embolic particles containing up to 9.4 wt% tantalum oxide were prepared and showed significant contrast compared to the undoped polystyrene particles. The X-ray contrast of the embolic particles was shown to be linear (R(2) = 0.9) with respect to the concentration of incorporated tantalum nanoparticles. A model was developed which showed that seventy-five 50 µm embolic particles containing 10% tantalum oxide could provide the same contrast as 5 cm of bone. Therefore, the synthesized particles would provide sufficient X-ray contrast to enable visualisation within a tumour.

Nanotechnologies for noninvasive measurement of drug release.

A wide variety of chemotherapy and radiotherapy agents are available for treating cancer, but a critical challenge is to deliver these agents locally to cancer cells and tumors while minimizing side effects from systemic delivery. Nanomedicine uses nanoparticles with diameters in the range of ∼1-100 nm to encapsulate drugs and target them to tumors. The nanoparticle enhances local drug delivery efficiency to the tumors via entrapment in leaky tumor vasculature, molecular targeting to cells expressing cancer biomarkers, and/or magnetic targeting. In addition, the localization can be enhanced using triggered release in tumors via chemical, thermal, or optical signals. In order to optimize these nanoparticle drug delivery strategies, it is important to be able to image where the nanoparticles distribute and how rapidly they release their drug payloads. This Review aims to evaluate the current state of nanotechnology platforms for cancer theranostics (therapeutic and diagnostic particles) that are capable of noninvasive measurement of release kinetics.

Incorporation of ophiobolin a into novel chemoembolization particles for cancer cell treatment.

PURPOSE: To design and synthesize chemoembolization particles for the delivery of Ophiobolin A (OphA), a promising fungal-derived chemotherapeutic, directly at the tumour location. To investigate cell death mechanism of OphA on a Rhabdomyosarcoma cancer (RD) cell line. Rhabdomyosarcoma is the most common soft tissue sarcoma in children; with a 5-year survival rate of between 30 and 65%. METHODS: Multimodal chemoembolization particles were prepared by sintering mesoporous silica nanoparticles, prepared by the sol-gel method, onto the surface of polystyrene microspheres, prepared by suspension copolymerisation. The chemoembolization particles were subsequently loaded with OphA. The effects of OphA in vitro were characterised by flow cytometry and nanoparticle tracking analysis (NanoSight). RESULTS: High loading of OphA onto the chemoembolization particles was achieved. The subsequent release of OphA onto RD cells in culture showed a 70% reduction in cell viability. OphA caused RD cells to round up and their membrane to bleb and caused cell death via apoptosis. OphA caused both an increase in the number of microvesicles produced and an increase in DNA content within these microvesicles. CONCLUSIONS: The prepared chemoembolization particles showed good efficacy against RD cells in culture.

Effects of mesoporous silica nanoparticles upon the function of mammalian sperm in vitro.

Nanomaterial-mediated delivery represents a promising technique for reproductive biology with a potential to improve the safety and efficacy of existing methodologies, including experimental gene therapy and sperm-mediated gene transfer. Mesoporous silica nanoparticles (MSNPs) have been characterised as a powerful and safe delivery tool, rendering them an excellent candidate for use in reproductive research. However, their effects upon mammalian gametes with highly specialised structure and functionality remain untested. Here, we show for the first time, that spherical MSNPs with hexagonal pore symmetry, functionalised with polyethileneimine and aminopropyltriethoxysilane, and optionally loaded with two common types of cargo (nucleic acid/protein), form strong associations with boar sperm following incubation in vitro and do not exert negative effect upon the main parameters of sperm function, including motility, viability, acrosomal status and DNA fragmentation index. Our findings provide a rationale for the use of MSNPs for the transfer of investigative, diagnostic and/or therapeutic compounds into mammalian sperm. FROM THE CLINICAL EDITOR: Functionalized mesoporous silica nanoparticles (MSNPs) are demonstrated as efficient agents for the transfer of investigative, diagnostic, and/or therapeutic compounds into mammalian sperm. This promising technique has the potential to improve the safety and efficacy of existing methodologies, including experimental gene therapy and sperm-mediated gene transfer.

Scaffold-Forming Collagen and Motor-Endplate Expressing Muscle Cells for Porcine Laryngoplasty.

OBJECTIVE: Vocal fold paralysis impairs quality of life, and no curative injectable therapy exists. We evaluated injection of a novel in situ polymerizing (scaffold-forming) collagen in the presence and absence of muscle-derived motor-endplate expressing cells (MEEs) to promote medialization and recurrent laryngeal nerve (RLN) regeneration in a porcine model of unilateral vocal fold paralysis. METHODS: Twelve Yucatan minipigs underwent right RLN transection. Autologous muscle progenitor cells were isolated from muscle biopsies, differentiated, and induced to MEEs. Three weeks after RLN injury, animals received injections of collagen, collagen containing MEEs, or saline into the paralyzed right vocal fold. Stimulated laryngeal electromyography and acoustic vocalization were used for function assessments. Larynges were harvested and underwent histologic, gene expression, and further quantitative analyses. RESULTS: Injections were well-tolerated, with the collagen scaffold showing immunotolerance and collagen-encapsulated MEEs remaining viable. Collagen-treated paralyzed vocal folds showed increased laryngeal adductor muscle volumes relative to that of the uninjured side, with those receiving MEEs and collagen showing the highest volumes. Muscles injected with MEEs and collagen demonstrated increased expression of select neurotrophic (BDNF and NTN1), motor-endplate (DOK7, CHRNA1, and MUSK), and myogenic (MYOG and MYOD) related genes relative to saline controls. CONCLUSION: In a porcine model of unilateral vocal fold paralysis, injection of in situ polymerizing collagen in the absence and presence of MEEs enhanced laryngeal adductor muscle volume, modulated expression of neurotrophic and myogenic factors, and avoided adverse material-mediated immune responses. Further study is needed to determine long-term functional outcomes with this novel therapeutic approach. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Tissue-Engineered Implant for Hemilaryngectomy Reconstruction with Recurrent Laryngeal Nerve Injury.

OBJECTIVE: Laryngeal cancer resections often require excision of portions of the larynx along with sacrifice of the ipsilateral recurrent laryngeal nerve (RLN). In such cases, there are no reconstructive options that reliably restore laryngeal function, rendering patients with severe functional impairment. To address this unmet clinical need, we extend our evaluation of a 3-implant mucosal, muscle, cartilage reconstruction approach aimed at promoting functional laryngeal restoration in a porcine hemilaryngectomy model with ipsilateral RLN transection. METHODS: Six Yucatan mini-pigs underwent full-thickness hemilaryngectomies with RLN transection followed by transmural reconstruction using fabricated collagen polymeric mucosal, muscle, and cartilage replacements. To determine the effect of adding therapeutic cell populations, subsets of animals received collagen muscle implants containing motor-endplate-expressing muscle progenitor cells (MEEs) and/or collagen cartilage implants containing adipose stem cell (ASC)-derived chondrocyte-like cells. Acoustic vocalization and laryngeal electromyography (L-EMG) provided functional assessments and histopathological analysis with immunostaining was used to characterize the tissue response. RESULTS: Five of six animals survived the 4-week postoperative period with weight gain, airway maintenance, and audible phonation. No tracheostomy or feeding tube was required. Gross and histological assessments of all animals revealed implant integration and regenerative remodeling of airway mucosa epithelium, muscle, and cartilage in the absence of a material-mediated foreign body reaction or biodegradation. Early voice and L-EMG data were suggestive of positive functional outcomes. CONCLUSION: Laryngeal reconstruction with collagen polymeric mucosa, muscle, and cartilage replacements may provide effective restoration of function after hemilaryngectomy with RLN transection. Future preclinical studies should focus on long-term functional outcomes. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Early Changes in Porcine Larynges Following Injection of Motor-Endplate Expressing Muscle Cells for the Treatment of Unilateral Vocal Fold Paralysis.

OBJECTIVES: No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implications of muscle-derived motor-endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury. METHODS: Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post-injury. Harvested porcine larynges were examined for volume, gene expression, and histology. RESULTS: MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of videolaryngoscopy post-injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE-injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post-mortem, the MEE-injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR. CONCLUSIONS: Minimally invasive MEE injection appears to establish an early molecular and microenvironmental framework to encourage innate RLN regeneration. Longer follow-up is needed to determine if early findings will translate into functional contraction. LEVEL OF EVIDENCE: NA Laryngoscope, 134:272-282, 2024.

Whisper-like behavior in a non-human primate.

In humans, whispering has evolved as a counteractive strategy against eavesdropping. Some evidence for whisper-like behavior exists in a few other species, but has not been reported in non-human primates. We discovered the first evidence of whisper-like behavior in a non-human primate, the cotton-top tamarin (Saguinus oedipus), in the course of investigating their use of human-directed mobbing calls. We exposed a family of captive cotton-top tamarins to a supervisor who previously elicited a strong mobbing response. Simultaneous audio-video recordings documented the animals' behavioral and vocal responses in the supervisor's presence and absence. Rather than exhibiting a mobbing response and producing loud human-directed mobbing calls, the tamarins exhibited other anti-predator behaviors and produced low amplitude vocalizations that initially eluded our detection. A post-hoc analysis of the data was conducted to test a new hypothesis-the tamarins were reducing the amplitude of their vocalizations in the context of exposure to a potential threat. Consistent with whisper-like behavior, the amplitude of the tamarins' vocalizations was significantly reduced only in the presence of the supervisor. Due to its subtle properties, this phenomenon may have eluded detection in this species. Increasing evidence of whisper-like behavior in non-human species suggests that such low amplitude signaling may represent a convergence in a communication strategy amongst highly social and cooperative species.

Engineered collagen polymeric materials create noninflammatory regenerative microenvironments that avoid classical foreign body responses.

The efficacy and longevity of medical implants and devices is largely determined by the host immune response, which extends along a continuum from pro-inflammatory/pro-fibrotic to anti-inflammatory/pro-regenerative. Using a rat subcutaneous implantation model, along with histological and transcriptomics analyses, we characterized the tissue response to a collagen polymeric scaffold fabricated from polymerizable type I oligomeric collagen (Oligomer) in comparison to commercial synthetic and collagen-based products. In contrast to commercial biomaterials, no evidence of an immune-mediated foreign body reaction, fibrosis, or bioresorption was observed with Oligomer scaffolds for beyond 60 days. Oligomer scaffolds were noninflammatory, eliciting minimal innate inflammation and immune cell accumulation similar to sham surgical controls. Genes associated with Th2 and regulatory T cells were instead upregulated, implying a novel pathway to immune tolerance and regenerative remodeling for biomaterials.

Impact of Needle Selection on Survival of Muscle-Derived Cells When Used for Laryngeal Injections.

Objective: To describe how differing injector needles and delivery vehicles impact Autologous Muscle-Derived Cell (AMDC) viability when used for laryngeal injection. Methods: In this study, adult porcine muscle tissue was harvested and used to create AMDC populations. While controlling cell concentration (1 × 107 cells/ml), AMDCs including Muscle Progenitor Cells (MPCs) or Motor Endplate Expressing Cells (MEEs) were suspended in either phosphate-buffered saline or polymerizable (in-situ scaffold forming) type I oligomeric collagen solution. Cell suspensions were then injected through 23- and 27-gauge needles of different lengths at the same rate (2 ml/min) using a syringe pump. Cell viability was measured immediately after injection and 24- and 48-hours post-injection, and then compared to baseline cell viability prior to injection. Results: The viability of cells post-injection was not impacted by needle length or needle gauge but was significantly impacted by the delivery vehicle. Overall, injection of cells using collagen as a delivery vehicle maintained the highest cell viability. Conclusion: Needle gauge, needle length, and delivery vehicle are important factors that can affect the viability of injected cell populations. These factors should be considered and adapted to improve injectable MDC therapy outcomes when used for laryngeal applications.

Augmented phytotoxic effect of nanoencapsulated ophiobolin A.

Ophiobolin A is a secondary phytotoxic metabolite produced by some pathogenic fungal species responsible for severe plant diseases, considered to play a role in disease development and symptom appearance. Herein we investigated whether the phytotoxic activities of ophiobolin A against weed species could be improved by nanoencapsulation. Given the rapid natural degradation of the compound, it was hoped that nanoencapsulation would prolong the phytotoxic effects or enhance the bioactivity, thus leading to improved weed control capabilities. This article presents an assessment of the effectiveness of encapsulated ophiobolin A on 11 commonly found weed species, compared to the pure ophiobolin, to the particle alone, and a combination of mixed particles and ophiobolin A, by applying the solution droplets to both intact or injured leaf surface, on the adaxial or abaxial side. The bioassays showed the improved efficacy of the encapsulated ophiobolin, and the need for leaf lesions to diffuse the particles into the tissues.[Formula: see text].

Open plan office space? If you're going to do it, do it right: A fourteen-month longitudinal case study.

There are compelling findings that open-plan office environments are associated with declines in employee wellbeing. In spite of this, the move towards shared office environments continues; yet there is a lack of research describing open-plan offices that have positive outcomes for workers. We describe a "best practice" open-plan fit-out of a law firm and provide data from occupants relating to their performance, well-being, and collegial relationships. Six months after moving to an open-plan office, staff were anonymously surveyed, and 24 were interviewed. Fourteen months later, occupants responded to a follow-up survey. Positive outcomes relating to aesthetics, collegiality, and communication were achieved through good technical design and thoughtful ergonomic assessment of the needs of employees and the requirements of their tasks. A gender difference emerged whereby female, but not male, workers in this environment reported feeling observed. This has implications for the relatively different impact these environments may have on workers. Thus, by following ergonomic principles to create open-plan offices that are 'safe by design' organizations can ameliorate many of the negative consequences associated with these environments.

Predictors of hospital readmission among older adults with cancer.

OBJECTIVE: Older adults with cancer are at higher risk for costly and potentially dangerous hospital readmissions. Identifying risk factors for readmission in this population is important for future prevention of readmission. MATERIALS AND METHODS: Hospital discharges among patients ≥ 65 years with solid tumors on non-surgical services from 2006-2011 were reviewed in this matched case-control study. We abstracted patient/cancer characteristics; functional status; fall risk; chemotherapy line; comorbidities; laboratory values; discharge parameters; and miscellaneous information (Do Not Resuscitate Order, pain scores) from medical records. Conditional logistic regression was used for univariate and multivariable analysis. RESULTS: This analysis included 184 case-patients readmitted within 30 days after discharge from the index admission and 184 sex- and age-matched control-patients discharged from index admission within three months of the cases with no readmission. Cases and controls had no differences in terms of primary cancer type, treatment, and index admission reason. Cases were more likely to have abnormal hemoglobin, albumin, sodium, and SGOT on discharge. Compared to those with ≤1 abnormal laboratory test, patients with 2 or more abnormal test results were 3 times more likely to be readmitted within 30 days. CONCLUSION: This study demonstrated that older adults with cancer who had at least 2 abnormal laboratory results (hemoglobin, albumin, sodium, and SGOT) at discharge were 3 times more likely to be readmitted within 30 days compared to those with ≤1 abnormal results. These laboratory values may be predictive of the risk of readmission, and should be monitored before discharge to potentially prevent readmission.

Friendship experiences among children with disabilities who attend mainstream Australian schools.

PURPOSE: To explore the experiences of friendship for children with disabilities who attend mainstream Australian schools. BACKGROUND: Being a friend is an important occupational role for all children. However, the literature suggests that physical inclusion of children with disabilities in mainstream schools does not necessarily develop social inclusion. METHODS: Phenomenology was used to explore friendship experiences of 10 primary school children with disabilities. FINDINGS: Five themes emerged from the data: (1) self-identity; (2) meaning of friendship; (3) classroom experiences; (4) playing together; (5) longing for friendship. These themes reflected the importance of friendship in the children's lives, the influence of the children's beliefs and values, and the impact of the attitudes and actions of educational staff and other students. IMPLICATIONS: Occupational therapists need to work collaboratively with educational staff, students, and their peers to create inclusive school settings that facilitate positive friendship experiences for children with disabilities.

A Phase II Trial of Older Adults With Metastatic Breast Cancer Receiving nab-Paclitaxel: Melding the Fields of Geriatrics and Oncology.

INTRODUCTION: Phase II clinical trials including geriatric assessment (GA) measures are critical for improving the evidence base for older adults with cancer. We assessed the efficacy and tolerability of nab-paclitaxel in older adults with metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients aged ≥ 65 years with MBC and ≤ 1 previous line of chemotherapy received 100 mg of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle. A GA was completed pre-chemotherapy, and the validated Cancer and Aging Research Group (CARG) chemotherapy toxicity risk score was calculated. Relationships between tolerability (number of courses, hospitalizations, dose reductions, and toxicity) and risk score were assessed using general linear models, Student t tests, and the Fisher test. Response rate and progression-free survival were evaluated using the Kaplan-Meier method. RESULTS: Forty patients (mean age, 73 years; range, 65-87 years) were included. The median number of cycles was 6, 75% (n = 30) of patients had ≥ 1 dose hold, and 50% (n = 20) had ≥ 1 dose reduction. Fifty-eight percent (n = 23) had treatment-related ≥ grade 3 toxicities, and 30% (n = 12) were hospitalized owing to toxicity. Thirty-five percent (n = 14) responded, and the median progression-free survival was 6.5 months (95% confidence interval, 5.5 months to undefined). Patients with intermediate/high toxicity risk scores had higher risk of grade ≥ 3 toxicity than those with low risk scores (odds ratio, 5.8; 95% confidence interval, 1.3-33.1; P = .01). A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations. CONCLUSIONS: Among older adults with MBC receiving weekly nab-paclitaxel, more than one-half experienced ≥ grade 3 chemotherapy toxicity. However, a GA-based risk score could predict treatment tolerability.

Precocious development of self-awareness in dolphins.

Mirror-self recognition (MSR) is a behavioral indicator of self-awareness in young children and only a few other species, including the great apes, dolphins, elephants and magpies. The emergence of self-awareness in children typically occurs during the second year and has been correlated with sensorimotor development and growing social and self-awareness. Comparative studies of MSR in chimpanzees report that the onset of this ability occurs between 2 years 4 months and 3 years 9 months of age. Studies of wild and captive bottlenose dolphins (Tursiops truncatus) have reported precocious sensorimotor and social awareness during the first weeks of life, but no comparative MSR research has been conducted with this species. We exposed two young bottlenose dolphins to an underwater mirror and analyzed video recordings of their behavioral responses over a 3-year period. Here we report that both dolphins exhibited MSR, indicated by self-directed behavior at the mirror, at ages earlier than generally reported for children and at ages much earlier than reported for chimpanzees. The early onset of MSR in young dolphins occurs in parallel with their advanced sensorimotor development, complex and reciprocal social interactions, and growing social awareness. Both dolphins passed subsequent mark tests at ages comparable with children. Thus, our findings indicate that dolphins exhibit self-awareness at a mirror at a younger age than previously reported for children or other species tested.