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Since the publication of the last Cellular Therapy and Stem Cell Transplant blueprint in 2013, Children's Oncology Group cellular therapy-based trials advanced the field and created new standards of care across a wide spectrum of pediatric cancer diagnoses. Key findings include that tandem autologous transplant improved survival for patients with neuroblastoma and atypical teratoid/rhabdoid brain tumors, one umbilical cord blood (UCB) donor was safer than two UCB donors, killer immunoglobulin receptor (KIR) mismatched donors did not improve survival for pediatric acute myeloid leukemia when in vivo T-cell depletion is used, and the depth of remission as measured by next-generation sequencing-based minimal residual disease assessment pretransplant was the best predictor of relapse for acute lymphoblastic leukemia. Plans for the next decade include optimizing donor selection for transplants for acute leukemia/myelodysplastic syndrome, using novel engineered cellular therapies to target a wide array of malignancies, and developing better treatments for cellular therapy toxicities such as viral infections and graft-vs-host disease., (© 2023 Wiley Periodicals LLC.)

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) posthematopoietic stem cell transplantation (HSCT) is often diagnosed using the modified Seattle (MS) or European Society for Blood and Marrow Transplantation (EBMT) criteria. We hypothesized that strict application of these criteria could affect the timing of diagnosis and incidence of SOS/VOD. We collected data on 215 transplants performed in 184 patients at a single pediatric hematopoietic stem cell transplantation center, which were divided into 3 cohorts. Clinical diagnosis and treatment of SOS/VOD was documented in 13% of transplants (cohort 1). On retrospective review, 49% of transplant events met either MS and/or EBMT criteria, however, were not diagnosed with SOS/VOD (cohort 2); remaining 38% of transplant events did not meet MS or EBMT criteria and were not diagnosed with SOS/VOD (cohort 3). Day+100 overall survival was significantly inferior for cohort 1 (78%) compared with cohorts 2 or 3 (92% and 95%, P=0.01) with no difference between cohorts 2 and 3 (P=0.5). Patients diagnosed with SOS/VOD >day+13 had worse day+100 overall survival when compared with those diagnosed ≤day13 (64.3% and 100%, respectively, P=0.02). This study highlights the value of careful clinical assessment to guide diagnosis and the need to refine diagnostic criteria for SOS/VOD in children., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

With limited data comparing hematopoietic cell transplant outcomes between myeloablative total body irradiation (TBI) containing and non-TBI regimens in children with de novo acute myeloid leukemia, the aim of this study was to compare transplant-outcomes between these regimens. Cox regression models were used to compare transplant-outcomes after TBI and non-TBI regimens in 624 children transplanted between 2008 and 2016. Thirty two percent (n=199) received TBI regimens whereas 68% (n=425) received non-TBI regimens. Five-year non-relapse mortality was higher with TBI regimens (22% vs. 11%, p<0.0001) but relapse was lower (23% vs. 37%, p<0.0001) compared to non-TBI regimens. Consequently, overall (62% vs. 60%, p=1.00) and leukemia-free survival (55% vs. 52%, p=0.42) did not differ between treatment groups. Grade II-IV acute GVHD was higher with TBI regimens (56% vs. 27%, p<0.0001) but not chronic GVHD. The 3-year incidence of gonadal or growth hormone deficiency was higher with TBI regimens (24% vs. 8%, p<0.001) but there were no differences in late pulmonary, cardiac or renal impairment. In the absence of a survival advantage, the choice of TBI or non-TBI regimen merits careful consideration with the data favoring non-TBI regimens to limit the burden of morbidity associated with endocrine dysfunction.

A disease risk index (DRI) that was developed for adults with hematologic malignancy who were undergoing hematopoietic cell transplantation is also being used to stratify children and adolescents by disease risk. Therefore, to develop and validate a DRI that can be used to stratify those with AML and ALL by their disease risk, we analyzed 2569 patients aged <18 years with acute myeloid (AML; n = 1224) or lymphoblastic (ALL; n = 1345) leukemia who underwent hematopoietic cell transplantation. Training and validation subsets for each disease were generated randomly with 1:1 assignment to the subsets, and separate prognostic models were derived for each disease. For AML, 4 risk groups were identified based on age, cytogenetic risk, and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2, 3, 5), high (7, 8), and very high (>8) risk groups was 78%, 53%, 40%, and 25%, respectively (P < .0001). For ALL, 3 risk groups were identified based on age and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2-4), and high (≥5) risk groups was 68%, 51%, and 33%, respectively (P < .0001). We confirmed that the risk groups could be applied to overall survival, with 5-year survival ranging from 80% to 33% and 73% to 42% for AML and ALL, respectively (P < .0001). This validated pediatric DRI, which includes age and residual disease status, can be used to facilitate prognostication and stratification of children with AML and ALL for allogeneic transplantation.

Objective: Currently, no evidence-based psychosocial clinical care pathways (PCCP) exist to triage psychosocial risk levels and guide delivery of psychosocial care to youth receiving a hematopoietic stem cell transplantation (HCT) and their families. The purpose of this paper is to describe the use of qualitative research methodologies to develop PCCP in pediatric HCT consistent with the Standards for Psychosocial Care developed for children with cancer., Methods: We previously used qualitative methodologies to interview parents to identify four principles to inform the development of PCCPs. Then in this study a focus group with parents and multidisciplinary clinicians was conducted to assess the acceptability of the PCCP, suggest modifications, and provide input on its use., Results: The PCCP is six-step pathway, starting with a standardized screening assessment with the Psychosocial Assessment Tool (PAT-HCT) that identifies the family's specific care needs. The focus group data support overall assessment with the PAT-HCT and the care principles underlying this approach., Conclusions: This PCCP is a systemic multidisciplinary model for providing psychosocial care that is ready for the next stage of development and evaluation in clinical care., (© 2019 Wiley Periodicals, Inc.)

A study was conducted using 3 groups of gestating gilts and sows (n = 98) to determine the effects of Pichia guilliermondii (Pg), a whole cell-inactivated yeast product (CitriStim; ADM Alliance Nutrition), on performance and immune parameters of dams and litters. Within 24 h of breeding, gilts and sows were allotted to 1 of 3 treatments consisting of a control (SC) diet or SC diet supplemented with 0.1 (S1) or 0.2% (S2) Pg. Dietary treatments were maintained through lactation. Colostrum and milk (day 14) samples were collected for IgA, IgG, and IgM analysis. Blood samples were collected from sows on day 110 of gestation (group 3 only), while at weaning for all 3 groups, and from piglets at 14 d of age for peripheral white blood cell counts and serum IgA, IgG, and IgM analysis. Inclusion of Pg resulted in an increase in number born alive as the level of Pg increased (12.49, 13.33, and 13.43 born alive per litter for SC, S1, and S2, respectively; linear effect [LS], P = 0.003). Additionally, the percentage of piglets weighing less than 0.9 kg at birth was reduced in sows provided Pg at 0.1% or 0.2% compared with control (LS, P = 0.006). Sows receiving Pg during gestation and lactation also weaned a greater number of piglets (10.31, 10.55, and 10.60 weaned per litter in control, 0.1% and 0.2% Pg, respectively; LS, P = 0.02). However, percent preweaning mortality was 17.58%, 19.38%, and 19.61% for control, 0.1%, and 0.2% Pg, respectively (LS, P = 0.02). There were no differences in gestation BW gain, farrowing (days 110 to 48 h postfarrowing) or lactation (day 110 to weaning) BW loss, number of mummies or stillborn, or piglets' individual birth or weaning weight. On day 110 of gestation, the neutrophil concentration (quadratic effect [QS], P = 0.03) and neutrophil:lymphocyte ratio (QS, P = 0.04) in peripheral blood were greater in S1 than SC, with S2 being intermediate. At weaning there was a linear increase in neutrophil concentration (P = 0.03), neutrophil:lymphocyte ratio (P = 0.01), and percentage of neutrophils in the leukocyte population (P = 0.01) as level of Pg increased in sow diets. In conclusion, Pg inclusion in sow diets linearly increased total number born alive and weaned, with no change in average birth or weaning weight, and decreased the number of lightweight pigs at birth. However, inclusion of Pg had no effect on immune parameters measured in milk, colostrum, or day 14 piglet serum, but increased the peripheral blood neutrophil concentration of gilts and sows., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m 2 /day (BSA ≤ .5 m 2 ), 12 g/m 2 /day (BSA > .5 to 1.0 m 2 ), or 14 g/m 2 /day (BSA > 1.0 m 2 ) on days -6 to -4; fludarabine 30 mg/m 2 /day on days -6 to -2; and a single fraction of 200 cGy total body irradiation on day -1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: While significant improvements have been made for children with acute lymphoblastic leukemia (ALL) in the United States over the past 20 years, black patients continue to have inferior outcomes. The full impact of socioeconomic variables on outcomes in this minority population is not entirely understood., Procedure: Disease characteristics, demographic, and socioeconomic status (SES) variables were collected on black (n = 44) and white (n = 178) patients diagnosed at the University of Alabama at Birmingham. Cox proportional hazard regression was used to evaluate the influence of SES and insurance status on survival., Results: As a cohort, 5-year overall survival (OS) was 87% (82-91%), with a median follow-up of 99 months. In univariable analysis, black race was not significantly associated with a higher risk of death or relapse and death. White and black patients with standard-risk leukemia had excellent outcomes, with 97% (91-99%) and 96% (75-99%) 5-year OS, respectively. In contrast, for high-risk disease, white patients had a statistically significant improved 5-year OS rates compared with black patients (79% [68-87%] vs. 52% [28-72%]). Black children were more likely to have public insurance, and, in multivariable analysis, this was associated with a trend toward an improved outcome. Black patients also had poorer census tract-level SES parameters, but these variables were not associated with survival., Conclusion: Our study demonstrates significantly inferior outcomes for black children with high-risk leukemia. These outcome disparities were not related to SES variables, including poverty or private insurance coverage, suggesting the involvement of other factors and highlighting the need for a prospective investigative analysis., (© 2016 Wiley Periodicals, Inc.)

We have carried out a pharmacological evaluation of arylmethylene quinuclidine derivatives interactions with human α3β4 nAChRs subtype, using cell-based receptor binding, calcium-influx, electrophysiological patch-clamp assays and molecular modeling techniques. We have found that the compounds bind competitively to the α3β4 receptor with micromolar affinities and some of the compounds behave as non-competitive antagonists (compounds 1, 2 and 3), displaying submicromolar IC(50) values. These evidences suggest a mixed mode of action for these compounds, having interactions at the orthosteric site and more pronounced interactions at an allosteric site to block agonist effects. One of the compounds, 1-benzyl-3-(diphenylmethylene)-1-azoniabicyclo[2.2.2]octane chloride (compound 3), exhibited poorly reversible use-dependent block of α3β4 channels. We also found that removal of a phenyl group from compound 1 confers a partial agonism to the derived analog (compound 6). Introducing a hydrogen-bond acceptor into the 3-benzylidene quinuclidine derivative (compound 7) increases agonism potency at the α3β4 receptor subtype. Docking into the orthosteric binding site of a α3β4 protein structure derived by comparative modeling accurately predicted the experimentally-observed trend in binding affinity. Results supported the notion that binding requires a hydrogen bond formation between the ligand basic nitrogen and the backbone carbonyl oxygen atom of the conserved Trp-149., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The pharmacokinetic and safety profiles of clinical drug candidates are greatly influenced by their requisite physicochemical properties. In particular, it has been shown that 2D molecular descriptors such as fraction of Sp3 carbon atoms (Fsp3) and number of stereo centers correlate with clinical success. Using the proteomic off-target hit rate of nicotinic ligands, we found that shape-based 3D descriptors such as the radius of gyration and shadow indices discriminate off-target promiscuity better than do Fsp3 and the number of stereo centers. We have deduced the relevant descriptor values required for a ligand to be nonpromiscuous. Investigating the MDL Drug Data Report (MDDR) database as compounds move from the preclinical stage toward the market, we have found that these shape-based 3D descriptors predict clinical success of compounds at preclinical and phase1 stages vs compounds withdrawn from the market better than do Fsp3 and LogD. Further, these computed 3D molecular descriptors correlate well with experimentally observed solubility, which is among well-known physicochemical properties that drive clinical success. We also found that about 84% of launched drugs satisfy either Shadow index or Fsp3 criteria, whereas withdrawn and discontinued compounds fail to meet the same criteria. Our studies suggest that spherical compounds (rather than their elongated counterparts) with a minimal number of aromatic rings may exhibit a high propensity to advance from clinical trials to market.

Three groups of gestating gilts and sows (Exp. 1; n = 98) were used to determine the effects of Pichia guilliermondii (Pg), a whole yeast product (CitriStim, ADM Alliance Nutrition), on dam and litter immune parameters. At breeding, gilts and sows were allotted to 1 of 3 treatments maintained through lactation: sow control (SC) diet or SC supplemented with 0.1 (S1) or 0.2% (S2) Pg. Pigs from groups 1 (Exp. 2) and 2 (Exp. 3) were weaned (21 d) and allotted in a 3 (SC, S1, or S2) × 2 [nursery with Pg (NPg) or without Pg (NC)] factorial arrangement in a randomized complete block design. In Exp. 2 blood samples were collected on days 5 and 28 postweaning for analysis. In Exp. 3, 36 pigs were individually penned and challenged with lipopolysaccharide (25 μg/kg BW intramuscular; 0 h). Individual BW, ADFI, and rectal temperature (RT) were collected at -48, -24, 0, 24, and 48 h and blood samples were collected at 0, 5, and 24 h for analysis. In Exp. 1, total neutrophil count (NEU) and neutrophil:lymphocyte ratio (NLR) were greater on day 110 of gestation (P < 0.05) in S1 than SC. At weaning there was a liner increase (P < 0.05) in NEU, NLR, and percentage of total leukocytes (PTL) that were NEU as level of Pg increased in sow diets. In Exp. 2, pigs from S1 had increased (P < 0.05) overall IgG than SC. The PTL that were eosinophils was greater in pigs from S2 fed NPg on day 5 than NC (P < 0.05) and increased in all pigs from S2 on day 28 (sow linear, P < 0.1). On day 28, total leukocytes and eosinophils were increased in pigs from SC [quadratic response (Q), P < 0.05]. In Exp. 3, a linear increase (P < 0.05) in ADFI was observed at -24 to 0 h, -48 to 0 h, and 24 to 48 h as the level of Pg increased in sow diets. There was a linear increase in RT at -48, -24, 0, and 5 h with increasing Pg inclusion in sow diets (P < 0.05). However, RT decreased more from 5 to 24 h in pigs from sows receiving Pg. The number of monocytes and PTL that were monocytes were higher in S2 compared to SC and S1 (P < 0.05). Also, NEU were reduced at 5 h in S1 (P < 0.05), NLR was lower in S2 at 0 h and S1 at 5 h, IL-1β concentration was greater in SC at 0 h and S1 at 5 h, and IL-6 concentration was greater in S2 at 0 h and S1 at 5 h (P < 0.05). Furthermore, blood urea N (BUN) was higher in NC at 0 and 5 h than NPg (P < 0.05). In conclusion, Pg appears to impact immune response criteria of sows and weaned pigs.

Based on pharmacophore elucidation and docking studies on interactions of benzylidene anabaseine analogs with AChBPs and α7 nAChR, novel spirodiazepine and spiroimidazoline quinuclidine series have been designed. Binding studies revealed that some of hydrogen-bond donor containing compounds exhibit improved affinity and selectivity for the α7 nAChR subtype in comparison with most potent metabolite of GTS-21, 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine. Hydrophobicity and rigidity of the ligand also contribute into its binding affinity. We also describe alternative pharmacophoric features equidistant from the carbonyl oxygen atom of the conserved Trp-148 of the principal face, which may be exploited to further design diverse focused libraries targeting the α7 nAChR., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The use of SharePoint® collaboration software for content management has become a critical part of today's drug discovery process. SharePoint 2010 software has laid a foundation which enables researchers to collaborate and search on various contents. The amount of data generated during a transition of a single compound from preclinical discovery to commercialization can easily range in terabytes, thus there is a greater demand of a chemically aware search algorithm that supplements SharePoint which enables researchers to query for information in a more intuitive and effective way. Thus by supplementing SharePoint with Chemically Aware™ features provides a great value to the pharmaceutical and biotech companies and makes drug discovery more efficient. Using several tools we have integrated SharePoint with chemical, compound, and reaction databases, thereby improving the traditional search engine capability and enhancing the user experience., Results: This paper describes the implementation of a Chemically Aware™ system to supplement SharePoint. A Chemically Aware SharePoint (CASP) allows users to tag documents by drawing a structure and associating it with the related content. It also allows the user to search SharePoint software content and internal/external databases by carrying out substructure, similarity, SMILES, and IUPAC name searches. Building on traditional search, CASP takes SharePoint one step further by providing a intuitive GUI to the researchers to base their search on their knowledge of chemistry than textual search. CASP also provides a way to integrate with other systems, for example a researcher can perform a sub-structure search on pdf documents with embedded molecular entities., Conclusion: A Chemically Aware™ system supplementing SharePoint is a step towards making drug discovery process more efficient and also helps researchers to search for information in a more intuitive way. It also helps the researchers to find information which was once difficult to find by allowing one to tag documents with molecular entities and integrating with image recognition software to find information from pdf documents.

AChBPs isolated from Lymnaea stagnalis (Ls), Aplysia californica (Ac) and Bulinus truncatus (Bt) have been extensively used as structural prototypes to understand the molecular mechanisms that underlie ligand-interactions with nAChRs [1]. Here, we describe docking studies on interactions of benzylidene anabaseine analogs with AChBPs and α7 nAChR. Results reveal that docking of these compounds using Glide software accurately reproduces experimentally-observed binding modes of DMXBA and of its active metabolite, in the binding pocket of Ac. In addition to the well-known nicotinic pharmacophore (positive charge, hydrogen-bond acceptor, and hydrophobic aromatic groups), a hydrogen-bond donor feature contributes to binding of these compounds to Ac, Bt, and the α7 nAChR. This is consistent with benzylidene anabaseine analogs with OH and NH(2) functional groups showing the highest binding affinity of these congeners, and the position of the ligand shown in previous X-ray crystallographic studies of ligand-Ac complexes. In the predicted ligand-Ls complex, by contrast, the ligand OH group acts as hydrogen-bond acceptor. We have applied our structural findings to optimizing the design of novel spirodiazepine and spiroimidazoline quinuclidine series. Binding and functional studies revealed that these hydrogen-bond donor containing compounds exhibit improved affinity and selectivity for the α7 nAChR subtype and demonstrate partial agonism. The gain in affinity is also due to conformational restriction, tighter hydrophobic enclosures, and stronger cation-π interactions. The use of AChBPs structure as a surrogate to predict binding affinity to α7 nAChR has also been investigated. On the whole, we found that molecular docking into Ls binding site generally scores better than when a α7 homology model, Bt or Ac crystal structure is used., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The interaction of NK inhibitory killer Ig-like receptors (KIRs) with self-MHC class I molecules mediates NK tolerance to self while conferring functional competence. Through single-cell analysis of intracellular IFN-gamma production and NK clone cytotoxicity we evaluated the resting NK repertoire, analyzing the responsiveness of NK subgroups expressing discrete combinations of non-KIR and KIR class I-specific receptors. CD94:NKG2A and Ig-like transcript 2 (ILT2)-expressing cells have a modest response to class I-negative target cells, but NK cells expressing inhibitory KIRs to self-MHC class I ligands, both HLA-B and HLA-C ligands, achieve significantly higher effector capacity. There is a dose effect of KIR for self-MHC on effector capacity, but even in the most highly responsive NK cells expressing more than one inhibitory KIR for self-MHC the presentation of only one cognate MHC ligand is sufficient to abolish response. Among KIR(+) cells there is preferential expression for inhibitory KIR for self-MHC. The likelihood of KIR expression is influenced by whether other KIRs are already expressed on the same cell, supporting a model of serial acquisition of KIR expression. These findings define how inhibitory receptor and autologous HLA interactions impact single-cell function and demonstrate that the resting human NK repertoire is highly attuned but variegated in response. These findings have important implications for the resting NK response to viral pathogens and malignancy, for donor selection in allogeneic hemopoietic cell transplantation, and for models of NK tolerance.

Purpose: The surgical management of osteosarcoma patients with unilateral pulmonary nodules is controversial. The authors reviewed their institutional experience to evaluate the incidence of occult contralateral metastases., Methods: Data were obtained retrospectively on all consecutive osteosarcoma patients from 1980 to 2002. Eighty-four patients with pulmonary nodules were identified. Forty-one had bilateral disease, and 43 had unilateral involvement by computed tomography (CT) scan., Results: All 43 patients with unilateral nodules underwent ipsilateral thoracotomies. Fifteen patients had negative exploration findings, and only 1 had pulmonary relapse. Of the 28 patients with metastases confirmed at initial thoracotomies, 14 had extensive pleural or extrapulmonary disease at initial thoracotomy followed by disease progression. The other 14 are separated into early versus late metastases, using 2 years from diagnosis as the cutoff point. Seven of the 9 (78%) patients with early metastases had or subsequently had contralateral disease; 6 were identified at staged contralateral thoracotomy and 1 had relapsed in the unexplored lung a year later. Only 1 of the 5 patients with late unilateral metastases had relapse in the contralateral side., Conclusions: Our data indicate that there is a high rate of contralateral involvement in osteosarcoma patients with unilateral nodules diagnosed by CT scan. Staged bilateral thoracotomies should be considered in osteosarcoma patients presenting with unilateral pulmonary disease on imaging studies within 2 years of diagnosis.

Misbisection of lines is thought to represent an attentional bias. When radial lines (intersection of the midsagittal and transverse planes) are presented below eye level, normal subjects are biased toward far peripersonal space in the visual modality and to near peripersonal space in the tactile modality. These errors may be related to a body centered, a retinotopic, or an object centered attentional bias. The purpose of this study was to contrast the body centered and retinotopic-objective centered hypotheses by having 12 normal subjects perform visual and tactile bisections of radial lines that are above and below eye level. The top of the page, which may be defined by retinotopic or object centered coordinates, contains the portion of the line that is most distant from our bodies when the page is below eye level. However, above eye level, the top of a radial line would be the portion of the page that is most proximal to our bodies. We observed that when stimuli are presented below eye level, normal subjects have a visual bias toward far peripersonal space or the top of the page or both, and have a tactile bias in the opposite direction. In the above eye position we found no overall bias in either modality. Because above eye level the body centered bias should have remained the same but the retinotopic or object centered bias should have reversed, our results suggest that the body and object centered or retinotopic biases, which are oriented in opposite directions, nullified each other.