Quality Improvement Initiative to Improve Time and Adherence to Revaccination after Hematopoietic Cell Transplantation: Implementation of a Revaccination Clinic within the Transplantation Program.

Revaccination after hematopoietic cell transplantation (HCT) is critical to prevent morbidity and mortality from vaccine-preventable illnesses. The global aim of our quality improvement initiative was to enhance timely, correct, and effective revaccination after pediatric HCT. The SMART aim of our project was to decrease median unvaccinated time by 4 months by decreasing the time to vaccine eligibility, time from eligibility to vaccine initiation, and time to completion of the vaccine series. A multidisciplinary group performed a cross-sectional quantitative and qualitative evaluation of revaccination practices at our institution. We identified factors associated with delayed, incorrect, or incomplete revaccination. Several plan-do-study-act interventions were implemented to address these drivers, including revising immune readiness criteria, increasing auditing of primary care administered immunizations, and, importantly, establishing a dedicated revaccination clinic within the HCT clinic at our center. The time to vaccine eligibility decreased from 12.6 months to 10 months (a 20% decrease), and the time to complete the vaccine series decreased from 19.3 months to 15.7 months (a 19% decrease). With a quality improvement initiative, we addressed the many causes of delayed or incomplete revaccination post-HCT and through a team-based approach successfully decreased the time to vaccine start and time to vaccine completion at our center.

A Retrospective Review of Revaccination Patterns in Pediatric Hematopoietic Stem Cell Transplantation Recipients.

Background: After a hematopoietic stem cell transplantation (HSCT), patients are left with little to no immunity to prevent infections. Importantly, this includes immunity gained from previous exposures, including vaccinations. This loss of immunity is a direct result of previous chemotherapy, radiation, and conditioning regimens the patients receive. It is critical to revaccinate patients post-HSCT to ensure protective immunity against vaccine-preventable diseases. Before 2017, all patients at our institution were referred to their pediatrician at approximately 12-month post-HSCT to be revaccinated. Clinical concern was raised at our institution regarding nonadherence and errors in vaccine schedules. Methods: To understand the magnitude of the problem with revaccination, we performed an internal audit of post-vaccine adherence in patients who received an HSCT between 2015 and 2017. A multidisciplinary team was developed to review the audit results and make recommendations. Results: This audit revealed delays in the initiation of the vaccine schedule, incomplete adherence to the recommended revaccination schedule, and errors in administration. Discussion: Based on the review of the data, the multidisciplinary team recommended an approach for systematic assessment of vaccine readiness and centralization of the administration of vaccines to be done within the stem cell transplant outpatient center.

CD3+/CD19+ Depleted Matched and Mismatched Unrelated Donor Hematopoietic Stem Cell Transplant with Targeted T Cell Addback Is Associated with Excellent Outcomes in Pediatric Patients with Nonmalignant Hematologic Disorders.

Unrelated donor hematopoietic stem cell transplantation (HSCT) is increasingly being used to cure nonmalignant hematologic diseases (NMHD) in patients who lack HLA matched related donors. Both graft rejection and graft-versus-host disease (GVHD) remain major barriers to safe and effective transplant for these patients requiring unrelated donors. Partial T cell depletion combined with peripheral stem cell transplantation (pTCD-PSCT) has the potential advantages of providing a high stem cell dose to facilitate rapid engraftment, maintaining cells that may facilitate engraftment, and decreasing GVHD risk compared with T cell-replete HSCT. Here, we report a single-institution, retrospective experience of unrelated donor pTCD-PSCT for pediatric patients with NMHD. From 2014 to 2017, 12 pediatric patients with transfusion-dependent NMHD underwent matched unrelated donor (MUD) or mismatched unrelated donor (MMUD) pTCD HSCT in our center using disease-specific conditioning. Donor PSCs underwent CD3+ T cell and CD19+ B cell depletion using CliniMACS, followed by a targeted addback of 1 × 105 CD3+ T cells/kg to the graft before infusion. All 12 patients demonstrated rapid trilinear engraftment. At a median follow-up of 740days (range, 279 to 1466), all patients were alive with over 92% total peripheral blood donor chimerism and without transfusion dependence or recurrence of their underlying hematologic disease. Immune reconstitution was rapid and comparable with T cell-replete HSCT. No patients developed severe acute GVHD (grades III to IV) or chronic extensive GVHD, and all patients had discontinued systemic immune suppression. Viral reactivations were common, but no patient developed symptoms of life-threatening infectious disease. Our data indicate that MUD and MMUD pTCD-PSCTs are safe and effective approaches that enable rapid engraftment and immune reconstitution, prevent severe GVHD, and expand availability of HSCT to any patients with NMHD who have closely MUDs.

Successful treatment of pulmonary mucormycosis in two pediatric hematopoietic stem cell transplant patients.

Pulmonary mucormycosis diagnosed immediately after hematopoietic stem cell transplantation frequently portends a poor prognosis. However, here we describe two cases in children that were treated successfully to highlight the efficacy of a multidisciplinary approach. Despite diagnosis in the immediate post-transplant period and requirement for ongoing immunosuppression to prevent or treat GVHD, both are long-term survivors due to early surgical debridement with transfusion support and prompt initiation of targeted antifungal therapy. In the absence of evidence-based treatment guidelines, survival of pulmonary mucormycosis is achievable even in high-risk patients with a multidisciplinary team to guide management.

A randomized controlled trial of exercise in spinal and bulbar muscular atrophy.

OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA). METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up and go, sit-to-stand test, health-related quality of life, creatine kinase, and insulin-like growth factor-1. RESULTS: Functional exercise was well tolerated but did not lead to significant group differences in the primary outcome measure or any of the secondary measures. The functional exercise did not produce significantly more adverse events than stretching, and was not perceived to be difficult. To determine whether a subset of the subjects may have benefited, we divided them into high and low functioning based on baseline AMAT scores and performed a post hoc subgroup analysis. Low-functioning individuals receiving the intervention increased AMAT functional subscale scores compared to the control group. INTERPRETATION: Although these trial results indicate that functional exercise had no significant effect on total AMAT scores or on mobility, strength, balance, and quality of life, post hoc findings indicate that low-functioning men with SBMA may respond better to functional exercises, and this warrants further investigation with appropriate exercise intensity.

Assessing function and endurance in adults with spinal and bulbar muscular atrophy: validity of the adult myopathy assessment tool.

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA). Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer disease duration (r = -0.29; P < 0.03) and lower serum androgen levels (r = 0.49-0.59; P < 0.001). The AMAT was significantly correlated with strength and functional status (r = 0.82-0.88; P < 0.001). The domains of the AMAT exhibited good internal consistency (Cronbach's α = 0.77-0.89; P < 0.001). Conclusions. The AMAT is a standardized, performance-based tool that may be used to assess functional limitations and muscle endurance. The AMAT has good internal consistency, and the construct validity of the AMAT is supported by its significant associations with hormonal, strength, and functional characteristics of adults with SBMA. This trial is registered with Clinicaltrials.gov identifier NCT00303446.

Predictors of functional shoulder recovery at 1 and 12 months after breast cancer surgery.

The objective of this study are (1) to determine if upper extremity function, as represented by shoulder ROM, self-reported symptoms and upper extremity functional limitations in activities of daily living could be predictively related to demographic and cancer characteristics post-surgery for breast cancer. And (2) to examine if variables related to early onset impairment contribute to late onset impairments in women after breast cancer surgery. Subjects were assessed preoperatively and 1, 3, 6, 9, and 12+ months post breast cancer surgery for impairments and symptoms and at 12+ months for shoulder functional limitations using a physical therapy surveillance model. Body weight, shoulder ROM, manual muscle testing, and upper limb volume were recorded. At 12+ months, the Harvard Alumni Health Study Physical Activity Questionnaire, and an Upper Limb Disability Questionnaire were administered. Symptoms and ROM impairments were compared by functional limitations. Characteristics significantly associated with early ROM impairment (but not later impairment) were axillary lymph node dissection, removal of ≥15 nodes, mastectomy surgery and stage II breast cancer. Positive nodes, older age, and BMI≥25 were significantly associated with reduced shoulder ROM at 12+ months. At 12+ months, only 10 % of the patients experienced ROM impairments while rates of self-reported symptoms in the affected upper extremity at 12+ months were as follows: pain-49%, weakness-47.1%, numbness-55.9%, feeling tired-42.5%. The majority of patients used the affected upper extremity for reaching without limitation, but ≥35% reported limitation with household chores, carrying and lifting. Difficulty carrying and lifting could be predicted by BMI≥25 and use of the dominant affected upper limb. Different factors are associated with early versus later ROM loss. Symptoms reported by breast cancer survivors are frequently associated with functional limitations in upper extremity tasks and warrant intervention. Physical therapy using a prospective surveillance model of care may reduce severity of ROM loss, symptoms and functional upper extremity limitations 1 year after breast cancer surgery.

Racial disparities in physical and functional domains in women with breast cancer.

INTRODUCTION: African-American women are more likely than white women to have functional impairments after breast cancer (BC) surgery; however, no differences were found in self-reported health status surveys at 12+ months postsurgery. PURPOSE: This analysis compared white and African-American BC survivors' (BCS) health status, health-related quality of life, and the occurrence of physical impairments after BC treatment. METHODS: One hundred sixty-six women (130 white, 28 African-American, 8 other) were assessed for impairments preoperatively and at 1, 3, 6, 9, and 12+ months postsurgery. Health status was assessed at 12+ months using the Short Form Health Survey (SF36v2™). Analysis of variance estimated differences between groups for health status and impairment occurrence. RESULTS: No differences were found between groups for BC type, stage, grade, or tumor size; surgery type; or number of lymph nodes sampled. African-American BCS had more estrogen/progesterone receptor-negative tumors (p < 0.001; p = 0.036) and received radiation more frequently (p = 0.03). More African-American BCS were employed (p = 0.022) and reported higher rates of social activities (p = 0.011) but less recreational activities (p = 0.020) than white BCS. African-American BCS had higher rates of cording (p = 0.013) and lymphedema (p = 0.011) postoperatively. No differences were found in self-reported health status. CONCLUSION: In a military healthcare system, where access to care is ubiquitous, there were no significant differences in many BC characteristics commonly attributed to race. African-American women had more ER/PR-negative tumors; however, no other BC characteristics differed between racial groups. African-American women exhibited more physical impairments, although their BC treatment only differed regarding radiation therapy. This suggests that African-American BCS may be at higher risk for physical impairments and should be monitored prospectively for early identification and treatment.

Breast cancer-related lymphedema: comparing direct costs of a prospective surveillance model and a traditional model of care.

Secondary prevention involves monitoring and screening to prevent negative sequelae from chronic diseases such as cancer. Breast cancer treatment sequelae, such as lymphedema, may occur early or late and often negatively affect function. Secondary prevention through prospective physical therapy surveillance aids in early identification and treatment of breast cancer-related lymphedema (BCRL). Early intervention may reduce the need for intensive rehabilitation and may be cost saving. This perspective article compares a prospective surveillance model with a traditional model of impairment-based care and examines direct treatment costs associated with each program. Intervention and supply costs were estimated based on the Medicare 2009 physician fee schedule for 2 groups: (1) a prospective surveillance model group (PSM group) and (2) a traditional model group (TM group). The PSM group comprised all women with breast cancer who were receiving interval prospective surveillance, assuming that one third would develop early-stage BCRL. The prospective surveillance model includes the cost of screening all women plus the cost of intervention for early-stage BCRL. The TM group comprised women referred for BCRL treatment using a traditional model of referral based on late-stage lymphedema. The traditional model cost includes the direct cost of treating patients with advanced-stage lymphedema. The cost to manage early-stage BCRL per patient per year using a prospective surveillance model is $636.19. The cost to manage late-stage BCRL per patient per year using a traditional model is $3,124.92. The prospective surveillance model is emerging as the standard of care in breast cancer treatment and is a potential cost-saving mechanism for BCRL treatment. Further analysis of indirect costs and utility is necessary to assess cost-effectiveness. A shift in the paradigm of physical therapy toward a prospective surveillance model is warranted.

Segmental limb volume change as a predictor of the onset of lymphedema in women with early breast cancer.

OBJECTIVE: To demonstrate that segmental changes along the upper extremity occur before the onset of breast cancer-related lymphedema (BCRL). These changes may be subclinical in nature and may be predictive of the onset of chronic lymphedema. DESIGN: A retrospective subset analysis of a larger prospective cohort trial. PATIENT COHORT: A total of 196 patients provided consent and were enrolled in the prospective study. Subclinical lymphedema developed in 46 of these patients. Limb volume data were available for 45 of these 46 patients from visits before the onset of lymphedema and were used in this analysis. We compared this group with an age-matched control group without BCRL from the same cohort (n = 45). SETTING: Military hospital outpatient breast care center. METHODS: Women were enrolled and assessed preoperatively. Baseline measures of limb volume were obtained with the use of optoelectronic perometry, and reassessment was conducted at 1, 3, 6, 9, and 12 months postoperatively. BCRL was identified in 46 of 196 women at an average of 6.9 months postoperatively. A retrospective analysis was conducted in which we examined volume changes over four 10-cm segments of the limb at the visits before the onset of BCRL. By using repeated-measures multivariate analysis of variance, we compared segmental volumes between groups at preoperative baseline, time of diagnosis of BCRL, and time of follow-up after early intervention. Linear regression analysis was performed to determine the strength of the relationship between total limb volume change with segmental volumes at the time of diagnosis of BCRL. MAIN OUTCOME MEASUREMENTS: We hypothesized that segmental volume changes occur and can be measured in the limb before the onset of lymphedema. RESULTS: At arm segments 10-20 cm (P = .044) and 20-30 cm (P <.001), a significant volume increase was noted before the diagnosis of subclinical BCRL. Segmental volume changes correlated to the total limb volume (TLV) change. At segments 20-30 cm, the coefficient of determination was r(2) = 0.952, and at 10-20 cm it was r(2) = 0.845, suggesting that these segments predicted TLV changes. CONCLUSION: Serial interval assessment of limb volume segments may be an important clinical tool to detect early-onset lymphedema before TLV changes.

Digital stereophotogrammetry as a new technique to quantify truncal deformity: a pilot study in persons with osteogenesis imperfecta.

The objective of this pilot study was to determine the usability of stereophotogrammetry (SP) as a noninvasive technique for obtaining linear measures and anatomical data of the torso in people with osteogenesis imperfecta in comparison with clinical observations. Ten participants were recruited from subjects enrolled in ongoing institutional review board-approved osteogenesis imperfecta protocols at the National Institute of Child Health and Human Development. Using a Gulick tape measure, anthropometer, and the SP system proprietary software, linear measurements of the torso were taken. In addition, the presence or absence of specific torso deformities was documented from both clinical observation and evaluation of SP images. Measurements of torso diameter and circumference by SP demonstrated strong agreement with the manual measurements (intraclass correlation coefficient = 0.995 and 0.964, respectively). Substantial and statistically significant agreement was present between SP image evaluation and clinical observation for pectus carinatum (κ = 0.52 ± 0.23) and thoracic scoliosis (κ = 0.72 ± 0.12). The kappa values between clinical observation and SP evaluations of other torso deformities were not significant. The strong correlations and P values determined by this study demonstrate the potential value of SP in studying persons with truncal deformities. However, the weak agreement between SP and some clinical observations suggests that further development of SP image analysis tools is required before SP can be used as a standard method of diagnosis or assessment of treatment success.

Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial.

BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is caused by polyglutamine expansion in the androgen receptor, which results in ligand-dependent toxicity. Animal models have a neuromuscular deficit that is mitigated by androgen-reducing treatment. We aimed to assess the efficacy and safety of the 5α-reductase inhibitor dutasteride in patients with SBMA, and to identify outcome measures for use in future studies of the disease. METHODS: We undertook a randomised, double-blind, placebo-controlled, single-site clinical trial in ambulatory, symptomatic men with genetically confirmed SBMA. Participants were assigned by random number table to receive dutasteride (0·5 mg per day) or placebo orally for 24 months. Patients and investigators were masked to treatment allocation. The primary outcome measure was quantitative muscle assessment (QMA). The final efficacy analysis included all patients who were compliant with study treatment at 24 months. This trial was registered with ClinicalTrials.gov, NCT00303446. FINDINGS: 50 men were randomly assigned to treatment groups (25 dutasteride, 25 placebo), and 44 were included in the efficacy analysis (21 dutasteride, 23 placebo). At 24 months, the placebo group showed a decrease of 4·5% (-0·30 kg/kg) from baseline in weight-scaled muscle strength as indicated by QMA, and the dutasteride group had an increase in strength of 1·3% (0·14 kg/kg); the difference between groups (5·8%, 95% CI -5·9 to 17·6; p=0·28) was not significant. Prespecified secondary outcome measures of creatine kinase, muscle strength and function, motor nerve conduction, activities of daily living, and erectile function did not show a significant difference between the study groups in change from baseline. Quality of life, as measured by the physical component summary of the Medical Outcomes Study 36-item Short Form version 2, favoured dutasteride (change in score from baseline: placebo, -3·6%, vs dutasteride, 2·1%; p=0·01), whereas the mental component summary favoured placebo (3·3%vs -3·2%; p=0·03). The dutasteride group had fewer patients reporting falls than did the placebo group (9 vs 16; p=0·048); there were no other significant differences in reported adverse events. INTERPRETATION: Our study did not show a significant effect of dutasteride on the progression of muscle weakness in SBMA, although there were secondary indications of both positive and negative effects compared with placebo. A longer trial duration or larger number of patients might be needed to show an effect on disease progression. Performance testing, QMA, and quality of life measures were identified as potentially useful endpoints for future therapeutic trials.

An artistic exploration of inattention blindness.

An experiment about inattention blindness was conducted within the context of an art exhibition as opposed to a laboratory context in order to investigate the potential of art as a vehicle to study attention and its disorders. The project utilized a flash animation, Stealing Attention, that was modeled after the movie by Simons and Chabris (1999) but with significant experimental differences, involving context and staging, the emotional salience of the objects depicted, and the prior art viewing experience of participants. The study involved two components: observing if viewers watching an animation in a gallery could be distracted from noticing the disappearance of stolen museum antiquities (the targets) by the overlaid flashing images of a card game (the distractors) and then observing whether repetition of the depicted targets throughout the gallery installation could facilitate a re-direction of attention that allowed viewers to perceive the targets not initially noted in the animation. My findings were that, after viewing the entire installation and then re-viewing the animation, 64% of the viewers who did not initially remark on the targets in the animation were then able to see them. The discussion elaborates on these findings and then considers ways in which the implications of inattention blindness paradigms might be more fully rendered by uniting insights from the two disciplines of art and neuroscience than by either alone.

Pre-operative assessment enables early diagnosis and recovery of shoulder function in patients with breast cancer.

In order to determine the extent and time course of upper limb impairment and dysfunction in women being treated for breast cancer (BC), and followed prospectively, a novel physical therapy surveillance model post-treatment was used. Subjects included adult women with newly diagnosed, untreated, unilateral, Stage I to III BC, and normal physiological and biomechanical shoulder function. Subjects were excluded if they had a previous history of BC, or prior injury or surgery of the affected upper limb. Measurements included body weight, shoulder ranges of motion (ROM), manual muscle tests, pain levels, upper limb volume, and an upper limb disability questionnaire (ULDQ). Measurements were taken at baseline (pre-surgery), and 1, 3-6, and 12 months post-surgery. All subjects received pre-operative education and exercise instruction and specific physical therapy (PT) protocol after surgery including ROM and strengthening exercises. All measures of function were significantly reduced 1 month post-surgery, but most recovered to baseline levels by 1-year post-surgery. Some subjects developed signs of lymphedema 3-12 months post-surgery, but this did not compromise function. Shoulder abduction, flexion, and external rotation, but not internal rotation ROM, were associated with the ULDQ. Most women in this cohort undergoing surgery for BC who receive PT intervention may expect a return to baseline ROM and strength by 3 months. Those who do not reach baseline, often continue to improve and reach their pre-operative levels by 1-year post-surgery. Lymphedema develops independently of shoulder function 3-12 months post-surgery, necessitating continued monitoring. A prospective physical therapy model of surveillance allows for detection of early and later onset of impairment following surgery for BC in this specific cohort of patients.

Clinical features of spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. To characterize the natural history and define outcome measures for clinical trials, we assessed the clinical history, laboratory findings and muscle strength and function in 57 patients with genetically confirmed disease. We also administered self-assessment questionnaires for activities of daily living, quality of life and erectile function. We found an average delay of over 5 years from onset of weakness to diagnosis. Muscle strength and function correlated directly with serum testosterone levels and inversely with CAG repeat length, age and duration of weakness. Motor unit number estimation was decreased by about half compared to healthy controls. Sensory nerve action potentials were reduced in nearly all subjects. Quantitative muscle assessment and timed 2 min walk may be useful as meaningful indicators of disease status. The direct correlation of testosterone levels with muscle strength indicates that androgens may have a positive effect on muscle function in spinal and bulbar muscular atrophy patients, in addition to the toxic effects described in animal models.

Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis.

Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. We designed a proof-of-principle study to examine if one series of Alemtuzumab infusions in sIBM patients depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease. Thirteen sIBM patients with established 12-month natural history data received 0.3 mg/kg/day Alemtuzumab for 4 days. The study was powered to capture > or =10% increase strength 6 months after treatment. The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements. Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies. Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies. During a 12-month observation period, the patients' total strength had declined by a mean of 14.9% based on Quantitative Muscle Strength Testing. Six months after therapy, the overall decline was only 1.9% (P < 0.002), corresponding to a 13% differential gain. Among those patients, four improved by a mean of 10% and six reported improved performance of daily activities. The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8% during the observation period but an improvement by 11.4% (P < 0.001) after 6 months, reaching the level of strength recorded 12 months earlier. Depletion of peripheral blood lymphocytes, including the naive and memory CD8+ cells, was noted 2 weeks after treatment and persisted up to 6 months. The effector CD45RA(+)CD62L(-) cells, however, started to increase 2 months after therapy and peaked by the 4th month. Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50% (P < 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and alphaB-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased. This proof-of-principle study provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one series of Alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. These encouraging results, the first in sIBM, warrant a future study with repeated infusions

Art and the brain: the influence of art on Roger Shepard's studies of mental rotation.

This paper explores the influence of visual sources on Roger N. Shepard's 1971 mental rotation experiments and the centrality of ambiguity as one of his experimental and artistic concerns. Sources include Shepard's statements about ambiguity as expressed in the book, Mind Sights, and a recent interview. Parallel investigations of ambiguity by the contemporary artists Al Held and Robert Smithson are considered. Shepard utilized a wide range of visual sources while formulating his experimental design, namely Necker cube illusions, hypnopompic images, René Magritte, and M.C. Escher. In addition, he drew upon key art historical theses of the time, such as Ernst Gombrich's theories about schemas. For Shepard as for Gombrich, the world of appearances is a world of ambiguity.