Managing the risks and benefits of clinical research in response to a pandemic.

Introduction: The coronavirus disease 2019 (COVID-19) created major disruptions at academic centers and healthcare systems globally. Clinical and Translational Science Awards (CTSA) fund hubs supported by the National Center for Advancing Translational Sciences provideinfrastructure and leadership for clinical and translational research at manysuch institutions. Methods: We surveyed CTSA hubs and received responses from 94% of them regarding the impact of the pandemic and the processes employed for the protection of research personnel and participants with respect to the conduct of research, specifically for studies unrelated to COVID-19. Results: In this report, we describe the results of the survey findings in the context of the current understanding of disease transmission and mitigation techniques. Conclusions: We reflect on common practices and provide recommendations regarding lessons learned that will be relevant to future pandemics, particularly with regards to staging the cessation and resumption of research activities with an aim to keep the workforce, research participants, and our communities safe in future pandemics.

Procuring animals and culturing of eggs and embryos.

Echinoderms and especially echinoids have a rich history as model systems for the study of oogenesis, fertilization, and early embryogenesis. The ease of collecting and maintaining adults, as well as in obtaining gametes and culturing large quantities of synchronous embryos, is complemented by the ability to do biochemistry, reverse genetics, embryo manipulations and study gene regulatory networks. The diversity of species and developmental modes as well as unparalleled transparency in early developmental stages also makes echinoderms an excellent system in which to study evolutionary aspects of developmental biology. This chapter provides a practical guide to experimental methods for procuring adults and gametes, achieving synchronous in vitro fertilization, and culturing embryos through early larval stages for several echinoderm species representing four classes (Echinoidea, Asteroidea, Ophiuroidea, and Holothuroidea). We provide specific examples of protocols for obtaining adults and gametes and for culturing embryos of a selected number of species for experimental analysis of their development. The species were chosen to provide breadth across the phylum Echinodermata, as well as to provide practical guidelines for handling some of the more commonly studied species. For each species, we highlight specific advantages, and special note is made of key issues to consider when handling adults, collecting gametes, or setting and maintaining embryo cultures. Finally, information regarding interspecific crosses is provided.

Long-term consequences of electrical injury: neuropsychological predictors of adjustment.

OBJECTIVE: Electrical injury (EI) produces an assortment of consequences for individuals. Survivors perform poorly on measures of attention and mental speed, memory, and emotional functioning. Moreover, sequelae are not always reported immediately following injury and often increase over the months following injury. It remains unclear whether the observed increase in neuropsychological and emotional symptoms over time is attributable to the delayed physical effects of EI or other factors that arise subsequent to injury, such as difficulty adjusting to post-injury limitations. METHOD: The current study utilized archival data to compare the neuropsychological and emotional complaints of EI survivors at two points during recovery, hypothesizing that Time 1 data would predict participants' outcome at Time 2. Specifically, those with worse neuropsychological performance and greater depressive symptomatology at Time 1 would have worse long-term adjustment to injury and psychological symptomatology. RESULTS: Multiple regression analyses revealed a significant predictive effect of Time 1 neurocognitive performance and depressive symptomatology on Time 2 adjustment to injury, psychological distress, and return to work. Participants with greater depressive symptomatology endorsed during the initial neuropsychological evaluation had substantially more difficulty with overall psychosocial adjustment to electrical injury. Moreover, depressive symptomatology persisted or worsened over the course of recovery. CONCLUSIONS: Findings demonstrate that poor outcome 4 years after EI is largely predicated by early emotional sequelae. Early screening and specialized interventions are needed to address psychological symptomatology among EI survivors.

Verbal Fluency: Language or Executive Function Measure?

Measures of phonemic and semantic verbal fluency, such as FAS and Animal Fluency (Benton, Hamsher, & Sivan, 1989), are often thought to be measures of executive functioning (EF). However, some studies (Henry & Crawford, 2004a , 2004b , 2004c ) have noted there is also a language component to these tasks. The current exploratory factor-analytic study examined the underlying cognitive structure of verbal fluency. Participants were administered language and EF measures, including the Controlled Oral Word Association Test (FAS version), Animal Fluency, Boston Naming Test (BNT), Vocabulary (Wechsler Adult Intelligence Scale-III), Wisconsin Card-Sorting Test (WCST, perseverative responses), and Trail-Making Test-Part B (TMT-B). A 2-factor solution was found with the 1st factor, language, having significant loadings for BNT and Vocabulary, while the second factor was labeled EF because of significant loading from the WCST and TMT-B. Surprisingly, FAS and Animal Fluency loaded exclusively on to the language factor and not EF. The current results do not exclude EF as a determinant of verbal fluency, but they do suggest that language processing is the critical component for this task, even without significant aphasic symptoms. Thus, the results indicated that both letter (phonemic) and category (semantic) fluency are related to language, but the relationship to EF is not supported by the results.

Derivation of a Cross-Domain Embedded Performance Validity Measure in Traumatic Brain Injury.

OBJECTIVE: Performance validity assessment is increasingly considered standard practice in neuropsychological evaluations. The current study extended research on logistically derived performance validity tests (PVTs) by utilizing neuropsychological measures from multiple cognitive domains instead of from a single measure or a single cognitive domain. METHOD: A logistic-derived PVT was calculated using several measures from multiple cognitive domains, including verbal memory (California Verbal Learning Test-II Trial 5, Total Hits, and False Positives), attention (Brief Test of Attention Total score), and language (Boston Naming Test T-score, and Animal Fluency T-score). Due to its cross-domain nature, the cross-domain logistic-derived embedded PVT was hypothesized to have excellent classification accuracy for non-credible performance. Participants included 224 patients who completed all measures and were moderate to severe traumatic brain injury (STBI) patients (N = 66), possible mild TBI (MTBI-FAIL) patients who failed at least 2 independent PVTs (N = 67), and possible mild TBI patients who passed all PVTs (MTBI-PASS; N = 91). Logistic regression and ROC analyses were conducted on the MTBI-FAIL group and the STBI group. RESULTS: Multivariate analysis of variance indicated that the MTBI-FAIL group was significantly lower on all measures than the MTBI-PASS and the STBI groups. Using logistic regression, CVLT Total Hits, BTA, and the CVLT False Positives best differentiated between the MTBI-FAIL and STBI groups. The logistically derived PVT had excellent classification accuracy (area under the curve [AUC] = .84), with sensitivity at .54 when specificity was set at .90, higher than any individual variable. CONCLUSIONS: Findings support the use of this logistical-derived variable as an embedded PVT and support further research with this type of methodology.

Computer-Assisted Face Processing Instruction Improves Emotion Recognition, Mentalizing, and Social Skills in Students with ASD.

This study examined the extent to which a computer-based social skills intervention called FaceSay was associated with improvements in affect recognition, mentalizing, and social skills of school-aged children with Autism Spectrum Disorder (ASD). FaceSay offers students simulated practice with eye gaze, joint attention, and facial recognition skills. This randomized control trial included school-aged children meeting educational criteria for autism (N = 31). Results demonstrated that participants who received the intervention improved their affect recognition and mentalizing skills, as well as their social skills. These findings suggest that, by targeting face-processing skills, computer-based interventions may produce changes in broader cognitive and social-skills domains in a cost- and time-efficient manner.

Language-based embedded performance validity measures in traumatic brain injury.

No studies to date have investigated the Boston Naming Test (BNT) as an embedded performance validity test (PVT). This study investigated the classification accuracy of the Boston Naming Test (BNT) and the Verbal Fluency Test (FAS and Animal Fluency), as embedded PVTs in a compensation-seeking mild traumatic brain injury (MTBI) sample (N = 57) compared to a non-compensation-seeking moderate-to-severe TBI (STBI) sample (N = 61). Participants in the MTBI sample who failed two or more PVTs were included, as were STBI participants who passed all PVTs. The classification accuracy of the individual tests and a logistically derived combined (LANGPVT) measure were studied. Results showed significant group differences (p < .05) on BNT, Animal Fluency, and LANGPVT between the MTBI and STBI groups. However, receiver operating characteristic (ROC) analyses indicated that only LANGPVT had acceptable classification accuracy (area under the curve > .70). Setting specificity at approximately .90, the recommended LANGPVT cutoff scores had sensitivity of .26. Results indicated that, similar to other embedded PVTs, these measures had low sensitivity when adequate specificity levels were maintained. However, extremely low scores on these measures are unlikely to occur in non-compensation-seeking, non-language-impaired, STBI cases.

Progress in detecting cell-surface protein receptors: the erythropoietin receptor example.

Testing for the presence of specific cell-surface receptors (such as EGFR or HER2) on tumor cells is an integral part of cancer care in terms of treatment decisions and prognosis. Understanding the strengths and limitations of these tests is important because inaccurate results may occur if procedures designed to prevent false-negative or false-positive outcomes are not employed. This review discusses tests commonly used to identify and characterize cell-surface receptors, such as the erythropoietin receptor (EpoR). First, a summary is provided on the biology of the Epo/EpoR system, describing how EpoR is expressed on erythrocytic progenitors and precursors in the bone marrow where it mediates red blood cell production in response to Epo. Second, studies are described that investigated whether erythropoiesis-stimulating agents could stimulate tumor progression in cancer patients and whether EpoR is expressed and functional on tumor cells or on endothelial cells. The methods used in these studies included immunohistochemistry, Northern blotting, Western blotting, and binding assays. This review summarizes the strengths and limitations of these methods. Critically analyzing data from tests for cell-surface receptors such as EpoR requires understanding the techniques utilized and demonstrating that results are consistent with current knowledge about receptor biology.

The personal digital assistant (PDA) as a tool for telementoring endoscopic procedures.

The telementoring of surgical procedures is currently achieved via a wired infrastructure that usually requires sophisticated videoconference systems. This project represents the first step in assessing the potential for using handheld computers as a mobile alternative to current telementoring systems. Specifically, this project compares a handheld computer to a standard CRT monitor regarding their capability to accurately display video images from an endoscopic procedure. Video images from two previously recorded endoscopic procedures were transmitted from a standard VCR to: 1) a handheld computer (iPAQ 3670 running Pocket PC) via a wireless LAN and 2) a standard CRT monitor via a wired analog connection. The software-used on the handheld device was custom designed to allow 320 X 240 pixel video images to be broadcast in real time. Twenty-three surgical residents who had completed an endoscopy rotation were randomized to watch one of the two videotaped endoscopic procedures on the hand held computer or on the CRT monitor. After viewing the procedure, a ten-question quiz was used to assess the ability of each participant to recognize several anatomic landmarks. The result of each questionnaire was expressed as the percentage of correct responses. Using a crossover design, each participant then viewed the other videotaped procedure using the alternate device and completed a second quiz. The mean test score for each device was calculated, and these data was analyzed using a Student T test. The observed difference between the mean test score associated with the handheld device (77.93 +/- 11.26) and the CRT monitor (81.30 +/- 12.54) was not statistically significant (p<0.41). In addition, regardless of the device used, scores corresponding to video tape one were significantly higher than those recorded for video tape two (84.35 +/- 9.92 vs. 74.35 +/- 11.61; p < 0.01) All participants were able to recognize anatomic landmarks equally well when viewing broadcasted endoscopic procedures on a handheld display or a standard CRT monitor. Handheld computers may have a role in telementoring residents who are performing endoscopic procedures. Further research is needed to evaluate the integration of handheld devices into telementoring and robotic system to perform surgical procedures.

Caudal anesthesia in children: effect of volume versus concentration of bupivacaine on blocking spermatic cord traction response during orchidopexy.

UNLABELLED: In this study we compared the intensity and level of caudal blockade when two different volumes and concentrations of a fixed dose of bupivacaine were used. Fifty children, 1-6 yr old, undergoing unilateral orchidopexy received a caudal block with a fixed 2 mg/kg dose of bupivacaine immediately after the induction. Group 1 (n = 23) received 0.8 mL/kg of 0.25% bupivacaine, whereas Group 2 (n = 27) received 1.0 mL/kg of 0.2% bupivacaine. Epinephrine 1:400,000 and 0.1 mL of sodium bicarbonate per 10 mL of local anesthetic solution were added. There were no statistically significant differences between the two groups in their anesthesia, surgery, recovery, and discharge times. Fifteen patients (65.2%) in Group 1 required an increase in inspired halothane concentration to block hemodynamic and/or ventilatory response during spermatic cord traction, as compared with 8 patients (29.6%) in Group 2 (P = 0.022). In the recovery room, four (17.4%) patients in Group 1 required rescue treatment with fentanyl, versus two (7.4%) in Group 2 (P = 0.372). In children undergoing orchidopexy, a caudal block with a larger volume of dilute bupivacaine is more effective than a smaller volume of the standard 0.25% solution in blocking the peritoneal response during spermatic cord traction, with no change in the quality of postoperative analgesia. IMPLICATIONS: In children undergoing orchidopexy, a caudal block with a larger volume of dilute bupivacaine is more effective than a smaller volume of the more concentrated solution in blocking the peritoneal response during spermatic cord traction, with no change in the quality of postoperative analgesia.