Assessing the association between parents' math talk and children's math performance: A preregistered meta-analysis.

The home math environment has gained considerable attention as a potential cause of variation in children's math performance, and recent research has suggested positive associations between parents' math talk and children's mathematical performance. However, the extent to which associations reflect robust causal effects is difficult to test. In a preregistered meta-analysis, we assess the association between parents' math talk and children's math performance. Our initial search identified 24,291 potential articles. After screening, we identified 22 studies that were included in analyses (k = 280 effect sizes, n = 35,917 participants). A multilevel random effects meta-analysis was employed, finding that parents' math talk is significantly associated with children's math performance (b = 0.10, SE = 0.03, p = .002). We tested whether associations differ as a function of sample characteristics, observation context, observation length, type of math talk and math performance measured, and modeling approaches to math talk variable analysis. In addition, we tested whether associations are robust to the inclusion of strong baseline covariates and found that effects attenuated when children's domain-general and/or prior math abilities are included. We discuss plausible bounds of the effects of parents' math talk on children's mathematical performance to inform power analyses and experimental work on the impact of parents' math language on children's math learning.

Fraction Ball impact on student and teacher math talk and behavior.

We assessed the impacts of Fraction Ball-a novel suite of games combining the benefits of embodied guided play for math learning-on the math language production and behavior of students and teachers. In the Pilot Experiment, 69 fifth and sixth graders were randomly assigned to play four different Fraction Ball games or attend normal physical education class. The Efficacy Experiment was implemented to test improvements made through co-design with teachers with 160 fourth through sixth graders. Researchers observed and coded for use of math language and behavior. Playing Fraction Ball resulted in consistent increases of students' and teachers' use of fraction (SDs = 0.98-2.42) and decimal (SDs = 0.65-1.64) language and number line arithmetic, but not in whole number, spatial language, counting, instructional gesturing, questioning, and planning. We present evidence of the math language production in physical education and value added by Fraction Ball to support rational number language and arithmetic through group collaboration.

Standards for psychosocial care in pediatric cancer: adapted proposal for Latin American and Caribbean countries.

Objective: To highlight the objectives, achievements, challenges, and next steps for the World Health Organization's Global Initiative for Childhood Cancer (GICC) framework, a project designed to improve psychosocial care (PSC) in pediatric cancer centers across Latin America and the Caribbean (LAC). Methods: The project was launched in Peru, the first GICC focal country, in November 2020. The diagnosis phase included a survey and a semistructured interview with health professionals to assess PSC practices in institutions, and a needs assessment survey for caregivers. In the second phase, a strategic plan was developed to address the identified needs, including the adaptation of PSC standards, the establishment of multicenter working groups, the expansion of the proposal, and the development of materials. Results: The study found that PSC was not being adequately provided in accordance with international standards. Six adapted standards were proposed and validated, and more than 50 regional health professionals participated in online activities to support the project. The implementation process is currently ongoing, with the establishment of five multidisciplinary working groups, one regional committee, and the production of 16 technical outputs. Conclusion: This project represents a substantial step forward to improve PSC for pediatric patients with cancer and their families in LAC countries. The establishment of working groups and evidence-based interventions strengthen the proposal and its implementation. Development of health policies that include PSC according to standards is needed to achieve sustainable results in the quality of life of children with cancer and their families.

Engineered Cells as a Test Platform for Radiohaptens in Pretargeted Imaging and Radioimmunotherapy Applications.

Pretargeted imaging and radioimmunotherapy approaches are designed to have superior targeting properties over directly targeted antibodies but impose more complex pharmacology, which hinders efforts to optimize the ligands prior to human applications. Human embryonic kidney 293T cells expressing the humanized single-chain variable fragment (scFv) C825 (huC825) with high-affinity for DOTA-haptens (293T-huC825) in a transmembrane-anchored format eliminated the requirement to use other pretargeting reagents and provided a simplified, accelerated assay of radiohapten capture while offering normalized cell surface expression of the molecular target of interest. Using binding assays, ex vivo biodistribution, and in vivo imaging, we demonstrated that radiohaptens based on benzyl-DOTA and a second generation "Proteus" DOTA-platform effectively and specifically engaged membrane-bound huC825, achieving favorable tumor-to-normal tissue uptake ratios in mice. Furthermore, [86Y]Y-DOTA-Bn predicted absorbed dose to critical organs with reasonable accuracy for both [177Lu]Lu-DOTA-Bn and [225Ac]Ac-Pr, which highlights the benefit of a dosimetry-based treatment approach.

What matters when exploring fidelity when using health IT to reduce disparities?

BACKGROUND: Implementation of evidence-based interventions often involves strategies to engage diverse populations while also attempting to maintain external validity. When using health IT tools to deliver patient-centered health messages, systems-level requirements are often at odds with 'on-the ground' tailoring approaches for patient-centered care or ensuring equity among linguistically diverse populations. METHODS: We conducted a fidelity and acceptability-focused evaluation of the STAR MAMA Program, a 5-month bilingual (English and Spanish) intervention for reducing diabetes risk factors among 181 post-partum women with recent gestational diabetes. The study's purpose was to explore fidelity to pre-determined 'core' (e.g. systems integration) and 'modifiable' equity components (e.g. health coaching responsiveness, and variation by language) using an adapted implementation fidelity framework. Participant-level surveys, systems-level databases of message delivery, call completion, and coaching notes were included. RESULTS: 96.6% of participants are Latina and 80.9% were born outside the US. Among those receiving the STAR MAMA intervention; 55 received the calls in Spanish (61%) and 35 English (39%). 90% (n = 81) completed ≥ one week. Initially, systems errors were common, and increased triggers for health coach call-backs. Although Spanish speakers had more triggers over the intervention period, the difference was not statistically significant. Of the calls triggering a health coach follow-up, attempts were made for 85.4% (n = 152) of the English call triggers and for 80.0% (n = 279) of the Spanish call triggers (NS). Of attempted calls, health coaching calls were complete for 55.6% (n = 85) of English-language call triggers and for 56.6% of Spanish-language call triggers (NS). Some differences in acceptability were noted by language, with Spanish-speakers reporting higher satisfaction with prevention content (p = < 0.01) and English-speakers reporting health coaches were less considerate of their time (p = 0.03). CONCLUSIONS: By exploring fidelity by language-specific factors, we identified important differences in some but not all equity indicators, with early systems errors quicky remedied and high overall engagement and acceptability. Practice implications include: (1) establishing criteria for languge-equity in interventions, (2) planning for systems level errors so as to reduce their impact between language groups and over time; and (3) examining the impact of engagement with language-concordant interventions on outcomes, including acceptability. Trial Registration National Clinical Trials registration number: CT02240420 Registered September 15, 2014. ClinicalTrials.gov.

Brain-Computer Interfaces Systems for Upper and Lower Limb Rehabilitation: A Systematic Review.

In recent years, various studies have demonstrated the potential of electroencephalographic (EEG) signals for the development of brain-computer interfaces (BCIs) in the rehabilitation of human limbs. This article is a systematic review of the state of the art and opportunities in the development of BCIs for the rehabilitation of upper and lower limbs of the human body. The systematic review was conducted in databases considering using EEG signals, interface proposals to rehabilitate upper/lower limbs using motor intention or movement assistance and utilizing virtual environments in feedback. Studies that did not specify which processing system was used were excluded. Analyses of the design processing or reviews were excluded as well. It was identified that 11 corresponded to applications to rehabilitate upper limbs, six to lower limbs, and one to both. Likewise, six combined visual/auditory feedback, two haptic/visual, and two visual/auditory/haptic. In addition, four had fully immersive virtual reality (VR), three semi-immersive VR, and 11 non-immersive VR. In summary, the studies have demonstrated that using EEG signals, and user feedback offer benefits including cost, effectiveness, better training, user motivation and there is a need to continue developing interfaces that are accessible to users, and that integrate feedback techniques.

Predictive Value of Matrix Metalloproteinases and Their Inhibitors for Mortality in Septic Patients: A Cohort Study.

PURPOSE: Over 170 biomarkers are being investigated regarding their prognostic and diagnostic accuracy in sepsis in order to find new tools to reduce morbidity and mortality. Matrix metalloproteinases (MMPs) and their inhibitors have been recently studied as promising new prognostic biomarkers in patients with sepsis. This study is aimed at determining the utility of several cutoff points of these biomarkers to predict mortality in patients with sepsis. MATERIALS AND METHODS: A multicenter, prospective, analytic cohort study was performed in the metropolitan area of Bucaramanga, Colombia. A total of 289 patients with sepsis and septic shock were included. MMP-9, MMP-2, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-2, TIMP-1/MMP-9 ratio, and TIMP-2/MMP-2 ratio were determined in blood samples. Value ranges were correlated with mortality to estimate sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiving operating characteristic curve. RESULTS: Sensitivity ranged from 33.3% (MMP-9/TIMP-1 ratio) to 60.6% (TIMP-1) and specificity varied from 38.8% (MMP-2/TIMP-2 ratio) to 58.5% (TIMP-1). As for predictive values, positive predictive value range was from 17.5% (MMP-9/TIMP-1 ratio) to 70.4% (MMP-2/TIMP-2 ratio), whereas negative predictive values were between 23.2% (MMP-2/TIMP-2 ratio) and 80.9% (TIMP-1). Finally, area under the curve scores ranged from 0.31 (MMP-9/TIMP-1 ratio) to 0.623 (TIMP-1). CONCLUSION: Although TIMP-1 showed higher sensitivity, specificity, and negative predictive value, with a representative population sample, we conclude that none of the evaluated biomarkers had significant predictive value for mortality.

Clustering Gambling Disorder Patients with Lotteries as a Preferred Form of Gambling.

Few studies have focused on the specific subtype of gamblers who present lotteries as their main gambling problem. This study aimed to explore empirical subgroups of treatment-seeking patients who endorsed lotteries as their preferred form of gambling. The sample included n = 342 patients who were included in two-step cluster analysis procedures using sociodemographic and clinical measures as indicator variables. Three clusters were identified: (a) Cluster 1 (labeled as "severely impaired young men", n = 108, 31.6%) included mainly single young men that were employed, with short disorder duration, high gambling severity and high levels of comorbid psychopathology; (b) Cluster 2 (labeled as "moderate severity and highly functional", n = 120, 35.1%) included patients that were middle-aged, highly educated, married, employed, with high socioeconomic position indexes and functional personality traits; and (c) Cluster 3 (labeled as "older, moderately impaired patients", n = 114, 33.3%) included older patients, the highest percentage of separated or divorced subjects, high unemployment, low socioeconomic status and low levels of education. This study indicates that gambling disorder profiles characterized by lotteries as a preferred form of gambling constitute a heterogeneous group in which distinct, empirically based phenotypes can be identified. These factors should be taken into account for the development of reliable assessment instruments and for the design of effective prevention and treatment programs.

[Variables associated with mortality in 103 patients with anti-neutrophil cytoplasmic antibodies associated vasculitis]. / Comportamiento clínico y factores asociados a mortalidad temprana en una cohorte de pacientes chilenos con vasculitis asociadas a anticuerpos anti citoplasma de neutrófilos (VAA).

BACKGROUND: Cumulative survival in patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (VAA) is 88 and 78% at 1 and 5 years, respectively. Despite this, mortality continues to be 2.7 times higher than the general population. Differences in the clinical profile of VAA in different ethnicities have been observed. AIM: To identify factors at the time of diagnosis, associated with mortality at one year of follow-up and to describe the clinical characteristics of these patients. MATERIAL AND METHODS: We identified in local databases and reviewed clinical records of patients with VAA with at least one year of follow up in a clinical hospital. Demographic and laboratory parameters and clinical activity scores were analyzed. RESULTS: Of 103 patients with VAA identified, 65 met the inclusion criteria and were analyzed. Their age ranged from 45 to 63 years and 56% were women. Thirty-five patients (54%) were diagnosed as granulomatosis with Polyangiitis (GPA) and 30 patients (46%) with Microscopic Polyangiitis (MPA). The frequency of renal disease was 53% and pulmonary involvement occurred in 72%. At one year of follow-up 11 patients died resulting in a mortality of 17%. Seven patients died within three months after diagnosis. MPO ANCA were more common than PR3 ANCA. In the multivariate analysis, the presence of ophthalmological involvement, lung kidney syndrome and a Five Factor Score (FFS) of 1 or more were independent factors associated with mortality at one year. CONCLUSIONS: In these patients, pulmonary manifestations predominate. Lung kidney syndrome, ophthalmological involvement and a FFS score ≥ 1 were associated with mortality.

Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten.

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic γ- and ß-emitting isotope 177Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [177Lu]Lu-Gemini was prepared with no-carrier-added 177LuCl3 to a molar-specific activity of 123 GBq/µmol and radiochemical purity of more than 99%. The specificity of BsAb-177Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [177Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [177Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([177Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [177Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [177Lu]Lu-Gemini behaved similarly to [177Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [177Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor-to-normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [177Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [177Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [177Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [177Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [177Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered 177Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).

Triangulating on developmental models with a combination of experimental and nonexperimental estimates.

Plausible competing developmental models show similar or identical structural equation modeling model fit indices, despite making very different causal predictions. One way to help address this problem is incorporating outside information into selecting among models. This study attempted to select among developmental models of children's early mathematical skills by incorporating information about the extent to which models forecast the longitudinal pattern of causal impacts of early math interventions. We tested for the usefulness and validity of the approach by applying it to data from three randomized controlled trials of early math interventions with longitudinal follow-up assessments in the United States (Ns = 1,375, 591, 744; baseline age 4.3, 6.5, 4.4; 17%-69% Black). We found that, across data sets, (a) some models consistently outperformed other models at forecasting later experimental impacts, (b) traditional statistical fit indices were not strongly related to causal fit as indexed by models' accuracy at forecasting later experimental impacts, and (c) models showed consistent patterns of similarity and discrepancy between statistical fit and models' effectiveness at forecasting experimental impacts. We highlight the importance of triangulation and call for more comparisons of experimental and nonexperimental estimates for choosing among developmental models. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Design and Analytic Features for Reducing Biases in Skill-Building Intervention Impact Forecasts.

Despite policy relevance, longer-term evaluations of educational interventions are relatively rare. A common approach to this problem has been to rely on longitudinal research to determine targets for intervention by looking at the correlation between children's early skills (e.g., preschool numeracy) and medium-term outcomes (e.g., first-grade math achievement). However, this approach has sometimes over-or under-predicted the long-term effects (e.g., 5th-grade math achievement) of successfully improving early math skills. Using a within-study comparison design, we assess various approaches to forecasting medium-term impacts of early math skill-building interventions. The most accurate forecasts were obtained when including comprehensive baseline controls and using a combination of conceptually proximal and distal short-term outcomes (in the nonexperimental longitudinal data). Researchers can use our approach to establish a set of designs and analyses to predict the impacts of their interventions up to two years post-treatment. The approach can also be applied to power analyses, model checking, and theory revisions to understand mechanisms contributing to medium-term outcomes.

Hedges, mottes, and baileys: Causally ambiguous statistical language can increase perceived study quality and policy relevance.

There is a norm in psychology to use causally ambiguous statistical language, rather than straightforward causal language, when describing methods and results of nonexperimental studies. However, causally ambiguous language may inhibit a critical examination of the study's causal assumptions and lead to a greater acceptance of policy recommendations that rely on causal interpretations of nonexperimental findings. In a preregistered experiment, 142 psychology faculty, postdocs, and doctoral students (54% female), ages 22-67 (M = 33.20, SD = 8.96), rated the design and analysis from hypothetical studies with causally ambiguous statistical language as of higher quality (by .34-.80 SD) and as similarly or more supportive (by .16-.27 SD) of policy recommendations than studies described in straightforward causal language. Thus, using statistical rather than causal language to describe nonexperimental findings did not decrease, and may have increased, perceived support for implicitly causal conclusions.

"You did a great job building that!" Links between parent-child prosocial talk and spatial language.

We investigated the extent to which parents' prosocial talk and negations relate to the quantity and diversity of parents' spatial language production. We also examined similar associations among children. Participants included 51 children of ages 4-7 years and their parents recruited from South Florida. Most of the dyads included mothers and were Hispanic and bilingual. Dyads constructed a Lego house for 10 min. Sessions were transcribed and coded for instances of parent prosocial talk (praises, reflective statements, and behavior descriptions), child general positive statements (all positive contributions to the interaction), and parent and child negations (criticisms, corrections, and disapprovals) using the Dyadic Parent-Child Interaction Coding System. Transcripts were also coded for quantity and diversity of spatial language including shape terms (e.g., square), dimensional adjectives (e.g., little), orientations (e.g., turn), locations (e.g., middle), and spatial features/properties (e.g., edge). Parents' prosocial language, but not negations, were significantly associated with the quantity and diversity of parents' spatial language. Children's general positive statements were significantly associated with children's spatial language quantity. Exploratory data analyses also revealed significant associations between parent-child talk about shapes, dimensions, and spatial features and properties. Findings suggest that variability in parent-child prosocial and spatial talk during collaborative spatial play relates to aspects of their own-and each other's-spatial language production. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Efficacy of HER2-Targeted Intraperitoneal 225Ac α-Pretargeted Radioimmunotherapy for Small-Volume Ovarian Peritoneal Carcinomatosis.

Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally considered to be surgically incurable. Targeted α-therapy with the α-particle-emitting radionuclide 225Ac (half-life, 9.92 d) is a high-linear-energy-transfer treatment approach effective for small-volume disease and even single cells. Here, we report the use of human epidermal growth factor receptor 2 (HER2) 225Ac-pretargeted radioimmunotherapy (PRIT) to treat a mouse model of human EOC SKOV3 xenografts growing as peritoneal carcinomatosis (PC). Methods: On day 0, 105 SKOV3 cells transduced with a luciferase reporter gene were implanted intraperitoneally in nude mice, and tumor engraftment was verified by bioluminescent imaging (BLI). On day 15, treatment was started using 1 or 2 cycles of 3-step anti-HER2 225Ac-PRIT (37 kBq/cycle as 225Ac-Proteus DOTA), separated by a 1-wk interval. Efficacy and toxicity were monitored for up to 154 d. Results: Untreated PC-tumor-bearing nude mice showed a median survival of 112 d. We used 2 independent measures of response to evaluate the efficacy of 225Ac-PRIT. First, a greater proportion of the treated mice (9/10 1-cycle and 8/10 2-cycle; total, 17/20; 85%) survived long-term compared with controls (9/27, 33%), and significantly prolonged survival was documented (log-rank [Mantel-Cox] P = 0.0042). Second, using BLI, a significant difference in the integrated BLI signal area to 98 d was noted between controls and treated groups (P = 0.0354). Of a total of 8 mice from the 2-cycle treatment group (74 kBq total) that were evaluated by necropsy, kidney radiotoxicity was mild and did not manifest itself clinically (normal serum blood urea nitrogen and creatinine). Dosimetry estimates (relative biological effectiveness-weighted dose, where relative biological effectiveness = 5) per 37 kBq administered for tumors and kidneys were 56.9 and 16.1 Gy, respectively. One-cycle and 2-cycle treatments were equally effective. With immunohistology, mild tubular changes attributable to α-toxicity were observed in both therapeutic groups. Conclusion: Treatment of EOC PC-tumor-bearing mice with anti-HER2 225Ac-PRIT resulted in histologic cures and prolonged survival with minimal toxicity. Targeted α-therapy using the anti-HER2 225Ac-PRIT system is a potential treatment for otherwise incurable EOC.

Intraperitoneal Pretargeted Radioimmunotherapy for Colorectal Peritoneal Carcinomatosis.

Peritoneal carcinomatosis (PC) is considered incurable, and more effective therapies are needed. Herein we test the hypothesis that GPA33-directed intracompartmental pretargeted radioimmunotherapy (PRIT) can cure colorectal peritoneal carcinomatosis. Nude mice were implanted intraperitoneally with luciferase-transduced GPA33-expressing SW1222 cells for aggressive peritoneal carcinomatosis (e.g., resected tumor mass 0.369 ± 0.246 g; n = 17 on day 29). For GPA33-PRIT, we administered intraperitoneally a high-affinity anti-GPA33/anti-DOTA bispecific antibody (BsAb), followed by clearing agent (intravenous), and lutetium-177 (Lu-177) or yttrium-86 (Y-86) radiolabeled DOTA-radiohapten (intraperitoneal) for beta/gamma-emitter therapy and PET imaging, respectively. The DOTA-radiohaptens were prepared from S-2-(4-aminobenzyl)-1,4,7, 10-tetraazacyclododecane tetraacetic acid chelate (DOTA-Bn). Efficacy and toxicity of single- versus three-cycle therapy were evaluated in mice 26-27 days post-tumor implantation. Single-cycle treatment ([177Lu]LuDOTA-Bn 111 MBq; tumor dose: 4,992 cGy) significantly prolonged median survival (MS) approximately 2-fold to 84.5 days in comparison with controls (P = 0.007). With three-cycle therapy (once weekly, total 333 MBq; tumor dose: 14,975 cGy), 6/8 (75%) survived long-term (MS > 183 days). Furthermore, for these treated long-term survivors, 1 mouse was completely disease free (microscopic "cure") at necropsy; the others showed stabilized disease, which was detectable during PET-CT using [86Y]DOTA-Bn. Treatment controls had MS ranging from 42-52.5 days (P < 0.001) and 19/20 mice succumbed to progressive intraperitoneal disease by 69 days. Multi-cycle GPA33 DOTA-PRIT significantly prolongs survival with reversible myelosuppression and no chronic marrow (929 cGy to blood) or kidney (982 cGy) radiotoxicity, with therapeutic indices of 12 for blood and 12 for kidneys. MTD was not reached.

An unusual extranodal natural killer/T-cell lymphoma presenting as chronic laryngitis: A case report.

RATIONALE: Nasal-type, extranodal natural killer (NK)/T-cell lymphoma is a rare lymphoma. The tumor usually shows ulcerative and necrotic lesions in the nasal cavities and sinuses. Tissue involvement outside the nasal cavity is uncommon. PATIENT CONCERN: We describe a 30-year-old man with a 2-month history of hoarseness, weight loss, and dyspnea. DIAGNOSIS: Magnetic resonance image (MRI) showed edema of the larynx with obliteration of the airway. Laryngoscopic examination described necrotic tissue in the glottis and larynx. The biopsy showed chronic, necrotizing laryngitis, with no granulomas, vasculitis, or atypical cells. The immunologic and microbiologic study was negative. Later, after immunosuppressive therapy, the patient presented erythema and diffuse enlargement of the right arm. MRI showed myositis of the biceps and brachial muscles. Infection was rule out, and direct microscopy showed an extensive muscle infiltration by mononuclear cells and abundant mitosis. Immunohistochemistry was positive for CD3, CD8, Ki 67 (90%), and CD56 compatible with extranodal NK/T cell lymphoma. INTERVENTIONS: The patient initially received immunosuppression treatments (corticoids, cyclofosfamide, and Rituximab) with relapsing episodes. When lymphoma was diagnosed, chemotherapy was started. OUTCOMES: The patient died during chemotherapy. LESSONS: Nasal-type, extranodal NK/T-cell lymphoma should be suspected even when there are no classical findings of neoplasms on histology. Immunohistochemistry is mandatory to rule it out.

A Self-Assembling and Disassembling (SADA) Bispecific Antibody (BsAb) Platform for Curative Two-step Pretargeted Radioimmunotherapy.

PURPOSE: Many cancer treatments suffer from dose-limiting toxicities to vital organs due to poor therapeutic indices. To overcome these challenges we developed a novel multimerization platform that rapidly removes tumor-targeting proteins from the blood to substantially improve therapeutic index. EXPERIMENTAL DESIGN: The platform was designed as a fusion of a self-assembling and disassembling (SADA) domain to a tandem single-chain bispecific antibody (BsAb, anti-ganglioside GD2 × anti-DOTA). SADA-BsAbs were assessed with multiple in vivo tumor models using two-step pretargeted radioimmunotherapy (PRIT) to evaluate tumor uptake, dosimetry, and antitumor responses. RESULTS: SADA-BsAbs self-assembled into stable tetramers (220 kDa), but could also disassemble into dimers or monomers (55 kDa) that rapidly cleared via renal filtration and substantially reduced immunogenicity in mice. When used with rapidly clearing DOTA-caged PET isotopes, SADA-BsAbs demonstrated accurate tumor localization, dosimetry, and improved imaging contrast by PET/CT. When combined with therapeutic isotopes, two-step SADA-PRIT safely delivered massive doses of alpha-emitting (225Ac, 1.48 MBq/kg) or beta-emitting (177Lu, 6,660 MBq/kg) S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) payloads to tumors, ablating them without any short-term or long-term toxicities to the bone marrow, kidneys, or liver. CONCLUSIONS: The SADA-BsAb platform safely delivered large doses of radioisotopes to tumors and demonstrated no toxicities to the bone marrow, kidneys, or liver. Because of its modularity, SADA-BsAbs can be easily adapted to most tumor antigens, tumor types, or drug delivery approaches to improve therapeutic index and maximize the delivered dose.See related commentary by Capala and Kunos, p. 377.

Microplastic contamination and fluxes in a touristic area at the SE Gulf of California.

Microplastics (MPs) are long-lasting anthropogenic pollutants, observed in all types of natural environments. The MPs abundance and their temporal variability in beach sands, surface waters (manta trawl), and suspended sediments (sediment trap) were assessed in Mazatlán, Mexico, a tourism destination on the northern Pacific coast, under the hypothesis that MP contamination is influenced by rainfall and population density. The MP concentrations in beach sands from urban and rural areas nearby Mazatlán (4-36 MPs m-2) and in surface waters (1.7-2.0 MPs m-3) were comparable between type of sampling sites; whereas the MP fluxes in sediment trap samples varied widely (40-782 MPs m-2 day-1) with highest values during the rainfall season. The MPs recovered were mostly white/clear (48-54%), and the prevailing shapes were fragments in beach sands and surface waters (59-80%), and fibers (75%) in suspended sediments. The synthetic polymers polypropylene, polyethylene, and polyethylene terephthalate were the most abundant in the study area.

Spatial anxiety mediates the sex difference in adult mental rotation test performance.

Mental rotation ability is associated with successful advances in STEM (science, technology, engineering, and mathematics) education and occupations. Meta-analyses have shown consistent sex disparities in mental rotation, where men outperform women on one measure of mental rotation ability, the Mental Rotations Test (MRT). Spatial anxiety, or the fear and apprehension felt when completing a task that requires spatial thinking, was proposed as a mechanism explaining the relation between sex and mental rotation test performance. This study modified the Spatial Anxiety Scale (SAS) to include questions about how anxious individuals feel when they must mentally rotate items to accomplish a task (e.g., playing Tetris). An exploratory factor analysis was conducted to assess the factorial structure of the modified spatial anxiety scale. Three factor loadings were extracted representing the ability to navigate, mentally rotate objects, and visualize objects. Furthermore, we analyzed the role of spatial anxiety and trait anxiety as potential mediators of the relation between participant sex and mental rotation performance. Spatial anxiety partially mediated the link between the sex of the participants and the MRT performance controlling for trait anxiety. Only navigation and mental rotation anxiety significantly mediated the relation between participant sex and mental rotation performance. We posit spatial anxiety as a barrier to efficient and accurate spatial thinking, and suggest that reducing spatial anxiety has the potential to improve spatial skills and reduce sex differences in mental rotation test performance. To ascertain this, an experimental design can determine whether a reduction in spatial anxiety causes changes in mental rotation test scores.