Ethical futures in biological anthropology: Research, teaching, community engagement, and curation involving deceased individuals.

Although ethical reforms in biological anthropology have gained ground in recent years, there is still a scarcity of ethical standards for work involving historical documented collections (HDCs) at US museums and universities. These collections of deceased individuals were created in the late 19th to mid-20th centuries under anatomy laws that targeted socially marginalized communities and allowed for the dissection of these individuals without their consent. Due to the extensive information associated with the individuals and made available to researchers, these collections have served as foundational resources for theory and methods development in biological anthropology into the 21st century. Recognizing the need for ethical guidelines for research, teaching and training, community engagement, and curation involving HDCs, we held a workshop called "Ethical Futures for Curation, Research, and Teaching in Biological Anthropology" on November 15-17, 2021. Here we summarize the conversations and major points of consensus among the workshop participants on these topics in order to advance these ethical considerations more broadly across the field.

Phospholipid chlorohydrins as chlorine exposure biomarkers in a large animal model.

Chlorine is a toxic industrial chemical that has been used as a chemical weapon in recent armed conflicts. Confirming human exposure to chlorine has proven challenging, and there is currently no established method for analyzing human biomedical samples to unambiguously verify chlorine exposure. In this study, two chlorine-specific biomarkers: palmitoyl-oleoyl phosphatidylglycerol chlorohydrin (POPG-HOCl) and the lipid derivative oleoyl ethanolamide chlorohydrin (OEA-HOCl) are shown in bronchoalveolar lavage fluid (BALF) samples from spontaneously breathing pigs after chlorine exposure. These biomarkers are formed by the chemical reaction of chlorine with unsaturated phospholipids found in the pulmonary surfactant, which is present at the gas-liquid interface within the lung alveoli. Our results strongly suggest that lipid chlorohydrins are promising candidate biomarkers in the development of a verification method for chlorine exposure. The establishment of verified methods capable of confirming the illicit use of toxic industrial chemicals is crucial for upholding the principles of the Chemical Weapons Convention (CWC) and enforcing the ban on chemical weapons. This study represents the first published dataset in BALF revealing chlorine biomarkers detected in a large animal. Furthermore, these biomarkers are distinct in that they originate from molecular chlorine rather than hypochlorous acid.

Skin decontamination of Carfentanil in vitro.

Skin decontamination of Chemical Biological Radioactive and Nuclear (CBRN) materials involves the timely and effective removal of the contaminants from the skin surface. The current work evaluated Fuller's Earth & The Reactive Skin Decontaminant Lotion Kit (RSDL®) to investigate whether they were as efficacious against free base Carfentanil skin contamination as they are against chemical warfare agents. The in vitro methodology used allowed for evaluation of decontamination regimens as specified by the decontaminant manufacturer rather than as an application of a bolus dose left in situ for the study duration. A selection of novel decontaminants, including Dermal Decontamination Gel (DDGel), Trivorex®, itaconic acid (IA), N,N'-methylenebisacrylamide (MBA), 2-trifluoromethylacrylic acid (TFMAA) and NanoSan Sorb were also tested for efficacy. All the evaluated decontaminants were successful at removing the majority of the Carfentanil skin surface contamination. The current work has shown that the Fuller's Earth decontamination kit, removes as much (or more) free base carfentanil from the skin surface in comparison to other products tested in this study series.

Practical Characterization Strategies for Comparison, Qualification, and Selection of Cell Viability Detection Methods for Cellular Therapeutic Product Development and Manufacturing.

Cellular therapy development and manufacturing has focused on providing novel therapeutic cell-based products for various diseases. The International Organization for Standardization (ISO) has provided guidance on critical quality attributes (CQAs) that shall be considered when testing and releasing cellular therapeutic products. Cell count and viability measurements are two of the CQAs that are determined during development, manufacturing, testing, and product release. The ISO Cell Counting Standard Part 1 and 2 addressed the needs for improving the quality of cell counting results. However, there is currently no guidance on the qualification and selection of a fit-for-purpose cell viability detection method. In this work, we present strategies for the characterization and comparison of AO/PI and AO/DAPI staining methods using the heat-killed (HK) and low temperature/nutrient-deprived (LT/ND) cell death models to evaluate the comparability of cell viability measurements and identify potential causes of differences. We compared the AO/PI and AO/DAPI staining methods using HK and LT/ND-generated dead cells, investigated the staining time effects on cell viability measurements, and determined their viability linearity with different mixtures of live and dead cells. Furthermore, we validated AO/PI and AO/DAPI cell viability measurement with a long-term cell proliferation assay. Finally, we demonstrate a practical example of cell viability measurement comparison using AO/PI and AO/DAPI on antibiotic-selected transduced Jurkat and THP-1 cells to select a fit-for-purpose method for functional genomics screening. The proposed strategies may potentially enable scientists to properly characterize, compare, and select cell viability detection methods that are critical for cellular therapeutic product development and manufacturing.

The effects of episode spacing on adult's reports of a repeated event.

Witnesses' reports of repeated events have been the focus of much research; however, the spacing interval between each episode of the event has differed greatly. The aim of the current study was to determine whether spacing interval affects participants' memory reports. Adults (N = 217) watched one (n = 52) or four videos depicting workplace bullying. The repeated event participants watched the four videos all in one day (n = 55), one per day over four consecutive days (n = 60), or one every three days over 12 days (n = 50). One week after the last (or only) video, participants reported on that video and answered some reflective questions about the procedure. Repeated-event participants also reported on what usually happens across the videos. Single-event participants reported proportionally more accurate information about the target video than repeated-event participants, and spacing interval did not affect repeated event participants' accuracy. However, accuracy scores were close to ceiling while errors rates were at floor levels, preventing us from drawing strong conclusions. We found some evidence that episode spacing affected participants' perceptions of their memory performance. Overall, spacing may have a minimal effect on adults' memory for repeated events, but further research is required.

Evaluation of eight lateral flow tests for the detection of anti-SARS-CoV-2 antibodies in a vaccinated population.

BACKGROUND: Rapid determination of an individual's antibody status can be beneficial in understanding an individual's immune response to SARS-CoV-2 and for initiation of therapies that are only deemed effective in sero-negative individuals. Antibody lateral flow tests (LFTs) have potential to address this need as a rapid, point of care test. METHODS: Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. Samples were analysed on eight different brands of antibody LFT and an automated chemiluminescent microparticle immunoassay (CMIA) that identifies anti-spike antibodies which was used as our reference standard. RESULTS: All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n = 60), AZD1222 (AstraZeneca, n = 31), mRNA-1273 (Moderna, n = 2) and Undeclared Vaccine Brand (n = 2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies. CONCLUSIONS: These tests are demonstrated to be highly sensitive to detect raised antibody levels in vaccinated individuals. RDTs are low cost and rapid alternatives to ELISA based systems.

A prospective diagnostic evaluation of accuracy of self-taken and healthcare worker-taken swabs for rapid COVID-19 testing.

BACKGROUND: Rapid diagnostic tests (RDTs) developed for point of care detection of SARS-CoV-2 antigen are recommended by WHO to use trained health care workers to collect samples. We hypothesised that self-taken samples are non-inferior for use with RDTs to diagnose COVID-19. We designed a prospective diagnostic evaluation comparing self-taken and healthcare worker (HCW)-taken throat/nasal swabs to perform RDTs for SARS-CoV-2, and how these compare to RT-PCR. METHODS: Eligible participants 18 years or older with symptoms of COVID-19. 250 participants recruited at the NHS Test and Trace drive-through community PCR testing site (Liverpool, UK); one withdrew before analysis. Self-administered throat/nasal swab for the Covios® RDT, a trained HCW taken throat/nasal sample for PCR and HCW comparison throat/nasal swab for RDT were collected. RDT results were compared to RT-PCR, as the reference standard, to calculate sensitivity and specificity. FINDINGS: Seventy-five participants (75/249, 30.1%) were positive by RT-PCR. RDTs with self-taken swabs had a sensitivity of 90.5% (67/74, 95% CI: 83.9-97.2), compared to 78.4% (58/74, 95% CI: 69.0-87.8) for HCW-taken swabs (absolute difference 12.2%, 95% CI: 4.7-19.6, p = 0.003). Specificity for self-taken swabs was 99.4% (173/174, 95% CI: 98.3-100.0), versus 98.9% (172/174, 95% CI: 97.3-100.0) for HCW-taken swabs (absolute difference 0.6%, 95% CI: 0.5-1.7, p = 0.317). The PPV of self-taken RDTs (98.5%, 67/68, 95% CI: 95.7-100.0) and HCW-taken RDTs (96.7%, 58/60, 95% CI 92.1-100.0) were not significantly different (p = 0.262). However, the NPV of self-taken swab RDTs was significantly higher (96.1%, 173/180, 95% CI: 93.2-98.9) than HCW-taken RDTs (91.5%, 172/188, 95% CI 87.5-95.5, p = 0.003). INTERPRETATION: In conclusion, self-taken swabs for COVID-19 testing offer an accurate alternative to healthcare worker taken swabs for use with RDTs. Our results demonstrate that, with no training, self-taken throat/nasal samples can be used by lay individuals as part of rapid testing programmes for symptomatic adults. This is especially important where the lack of trained healthcare workers restricts access to testing.

Adaptation of a Modified Diet Quality Index to Quantify Healthfulness of Food-Related Toy Sets.

The objective of this cross-sectional study was to examine the construct validity of an adapted modified Diet Quality Index (aDQI) as a measure of the healthfulness of food-related toy sets for young children (3-8 years). A standardized online search was used to identify toy sets (n = 50) from 10 retailers. An aDQI score (aDQI score, range 0-50) was determined for each toy set, mean (standard deviation) = 28.7 (6.1). Regression analyses demonstrated a positive association between aDQI score and percentage of dairy, refined grains, protein, vegetables, and fruit and inverse association with percentage of desserts, sugar-sweetened beverages, and total number of servings. Sets contained more protein and fewer fruits than recommended. The aDQI score demonstrates construct validity to objectively assess the healthfulness of food-related toy sets. There is opportunity for toy manufacturers to make changes to improve the healthfulness in toy sets for young children, and future research can explore the impact of food-related toy sets on nutrition behaviors.

William Montague Cobb: Near the African diasporic origins of activist and biocultural anthropology.

William Montague Cobb, AB, MD, PhD, was the first African American PhD in anatomy and physical anthropology. He produced 1,100 publications while a professor at Howard University. His influence on the civil rights struggle from the 1930s to 1970s was profound as were his contributions to science and medical history. This article shows how he continued the activist and interdisciplinary traditions of African diasporic intellectuals and that these innovated what is today labeled biocultural anthropology, which focuses on the political, economic, and other societal influences on human biology and health. The human biology of the White "mainstream" has tended toward reductionism, biodeterminism, and eugenics. It drew a causal arrow from biology to society. Had they been able to listen to Black intellectuals, the world might have avoided the tragedy of mid-20th century eugenics and its long continuing biodeterministic shadow.

Utility of venous blood gases for the assessment of traumatic shock: a prospective observational study.

BACKGROUND: ABG samples are often obtained in trauma patients to assess shock severity. Venous blood gas (VBG) sampling, which is less invasive, has been widely used to assess other forms of shock. The study aim was to determine the agreement between VBG and ABG measurements in trauma. METHODS: Patients were enrolled at an Australian trauma centre between October 2016 and October 2018. Bland-Altman limits of agreement (LOA) between paired blood gas samples taken <30 min apart were used to quantify the extent of agreement. The impact of using only VBG measurements was considered using an a priori plan. Cases where venous sampling failed to detect 'concerning levels' were flagged using evidence-based cut-offs: pH ≤7.2, base deficit (BD) ≤-6, bicarbonate <21 and lactate ≥4. Case summaries of these patients were assessed by independent trauma clinicians as to whether an ABG would change expected management. RESULTS: During the study period 176 major trauma patients had valid paired blood gas samples available for analysis. The median time difference between paired measurements was 11 min (IQR 6-17). There was a predominance of men (81.8%) and blunt trauma (92.0%). Median Injury Severity Score was 13 (range 1-75) and inpatient mortality was 6.3%. Mean difference (ABG-VBG) and LOA between paired arterial and venous measurements were 0.036 (LOA -0.048 to 0.120) for pH, -1.27 mmol/L (LOA -4.35 to 1.81) for BD, -0.64 mmol/L (LOA -1.86 to 0.57) for lactate and -1.97 mmol/L (LOA -5.49 to 1.55) for bicarbonate. Independent assessment of the VBG 'false negative' cases (n=20) suggested an ABG would change circulatory management in two cases. CONCLUSIONS: In trauma patients VBG and ABG parameters displayed suboptimal agreement. However, in cases flagged as VBG 'false negative' independent review indicated that the availability of an ABG was unlikely to change management.

Development of chlorine-induced lung injury in the anesthetized, spontaneously breathing pig.

Chlorine is a toxic industrial chemical produced in vast quantities globally, being used in a range of applications such as water purification, sanitation and industrial processes. Its use and transport cannot be restricted; exposure may occur following accidental or deliberate releases. The OPCW recently verified the use of chlorine gas against civilians in both Syria and Iraq. Chlorine inhalation produces damage to the lungs, which may result in the development of an acute lung injury, respiratory failure and death. Treatment remains an intractable problem. Our objective was to develop a clinically relevant pre-clinical model of a moderate to severe lung injury in the pig. This would enable future assessment of therapeutic drugs or interventions to be implemented in the pre-hospital phase after exposure. Due to the irritant nature of chlorine, a number of strategies for exposing terminally anesthetized pigs needed to be investigated. A number of challenges (inconsistent acute changes in respiratory parameters; early deaths), resulted in a moderate to severe lung injury not being achieved. However, most pigs developed a mild lung injury by 12 h. Further investigation is required to optimize the model and enable the assessment of therapeutic candidates. In this paper we describe the exposure strategies used and discuss the challenges encountered in establishing a model of chlorine-induced lung injury. A key aim is to assist researchers navigating the challenges of producing a clinically relevant model of higher dose chlorine exposure where animal welfare is protected by use of terminal anesthesia.

Percutaneous absorption of Carfentanil in vitro.

Carfentanil is a synthetic opioid restricted to veterinary use due to its potency. Public health concerns have been raised as to the potential of carfentanil to exhibit toxicity after absorption via the percutaneous route following unintentional contamination. The current study measured the penetration of free base carfentanil through human, pig and rat skin using in vitro static diffusion cells. The human penetration rates were compared against literature toxicology values and indicated that, dependent on the contamination density, contamination area and residence time, skin decontamination and medical countermeasures may be required to ameliorate toxicity. The pig and rat skin penetration data will form the basis of future work to develop relevant in silico and in vivo models to further elucidate likely toxic effects and the medical strategies to mitigate against them.

"[This] system was not made for [you]:" A case for decolonial Scientia.

BACKGROUND: Sylvia Wynter's "recoded" form of science called decolonial Scientia (DS) is grounded in an understanding of humans as simultaneously biological and cultural. DS includes narrative interventions that destabilize Western scientific authority, and address limitations that empirical data collection and analysis place on capturing simultaneous realities. Therefore, Wynter's narrative "languaging" is both scientific critique and grounded in a tradition of Black radical imagining. AIMS: In this article, I use languaging to destabilize the canonical narrative tied to W. M. Cobb's production of the article "Race and Runners." The standard telling focuses on Cobb's examination of Owens' lower extremities to expose the fallacy of racial differences in athletic ability. Destabilization of the narrative allows for identifying relational complexities between actors involved in the canonical story - and identifying ideologies embedded within it that guide our deconstructions of biological race. My alter(ed)native subjectivity informs my use of languaging to argue that the relationship between narrative and research practices belie Western scientific/unscientific binaries. MATERIALS AND METHODS: Audiovisual and documentary sources of the public-facing "Race and Runners" story were subject to comparative analysis to verify the content and order of events in the canonical narrative. Letters focused on race and athletic ability obtained from the W. Montague Cobb Manuscript Collection at Howard University serve as "apocryphal" sources of information. Correspondence between Cobb and a representative member of the public named Howard Duncan took place within a period immediately before, during and after Cobb publishes "Race and Runners" in the Journal of Health and Physical Education. Contents were subject to a systematic analysis that involved reviewing documents to identify statements reflecting scientific practices, human interactions and relationships between race and athletic ability reflected in the canonical narrative. Contents were also examined for statements relevant to the narrative that departed from or added to the canonical story in the same three areas. Details regarding departures and additions were recorded along with the specific part of the narrative to which they corresponded. Narrative departures and additions were articulated with the canonical narrative in the interest of destabilizing it to identify "knots of ideas, histories and narratives that, contrary to Western science, can only be legible in relation to one another" (McKittrick, 2015b p. 2). RESULTS: Letters exchanged between Cobb and Duncan reveal dynamics that are obscured in the canonical storyline. For instance, Duncan's ability as a white male to assert himself as Cobb's peer demonstrates how racialized power is enacted through science. This is also reflected in Owens' position in the narrative as a voiceless object of knowledge. Letters also present Cobb's identity beyond being a "pioneer," rendering how he is studying and experiencing racism. This includes how he refuses to engage Duncan as a peer. DISCUSSION: More than mere stories, narratives are motivating and instructive forces that shape how we study human biology and use our research to oppose biological notions of race. Correspondence between Cobb and Duncan reveals how Western scientific ideologies that reinforce prescribed roles and boundaries are embedded in narratives. These ideologies can limit the transformative potential of our approaches to contesting biological notions of race.

The Road to Survival for Haemodynamically Unstable Patients With Open Pelvic Fractures.

Management of haemodynamically unstable pelvic ring injuries has been simplified into treatment algorithms to streamline care and emergent decision making in order to improve patient outcomes whilst decreasing mortality and morbidity. Pelvic ring injuries are most commonly a result of high-velocity and energy forces that exert trauma to the pelvic bones causing not only damage to the bone but the surrounding soft-tissue, organs, and other structures and are usually accompanied by injuries to other parts of the body resulting in a polytraumatised patient. Open pelvic fractures are a rare subset of pelvic ring fractures that are on the more severe end of the pelvic fracture continuum and usually produce uncontrolled haemorrhage from fractured bone, retroperitoneal haematomas, intraabdominal bleeding from bowel injury, soft tissue injuries to the anus, perineum, and genitals, fractures of the pelvic bones, causing bleeding from cancellous bone, venous, and arterial injuries combined with bleeding from concomitant injuries. This is a very complex and challenging clinical situation and timely and appropriate decisions and action are paramount for a positive outcome. Consequently, open pelvic fractures have an extremely high rate of mortality and morbidity and outcomes remain poor, despite evidence-based improvements in treatment, knowledge, and identification of haemorrhage; in the pre-hospital, critical care, and operative settings. In the future utilisation of haemostatic drugs, dressings, devices, and procedures may aid in the time to haemorrhage control.

Design and fabrication of a passive droplet dispenser for portable high resolution imaging system.

Moldless lens manufacturing techniques using standard droplet dispensing technology often require precise control over pressure to initiate fluid flow and control droplet formation. We have determined a series of interfacial fluid parameters optimised using standard 3D printed tools to extract, dispense and capture a single silicone droplet that is then cured to obtain high quality lenses. The dispensing process relies on the recapitulation of liquid dripping action (Rayleigh-Plateau instability) and the capturing method uses the interplay of gravitational force, capillary forces and liquid pinning to control the droplet shape. The key advantage of the passive lens fabrication approach is rapid scale-up using 3D printing by avoiding complex dispensing tools. We characterise the quality of the lenses fabricated using the passive approach by measuring wavefront aberration and high resolution imaging. The fabricated lenses are then integrated into a portable imaging system; a wearable thimble imaging device with a detachable camera housing, that is constructed for field imaging. This paper provides the full exposition of steps, from lens fabrication to imaging platform, necessary to construct a standalone high resolution imaging system. The simplicity of our methodology can be implemented using a regular desktop 3D printer and commercially available digital imaging systems.

Pro-invasive Effect of Proto-oncogene PBF Is Modulated by an Interaction with Cortactin.

CONTEXT: Metastatic disease is responsible for the majority of endocrine cancer deaths. New therapeutic targets are urgently needed to improve patient survival rates. OBJECTIVE: The proto-oncogene PTTG1-binding factor (PBF/PTTG1IP) is overexpressed in multiple endocrine cancers and circumstantially associated with tumor aggressiveness. This study aimed to understand the role of PBF in tumor cell invasion and identify possible routes to inhibit its action. Design, Setting, Patients, and Interventions: Thyroid, breast, and colorectal cells were transfected with PBF and cultured for in vitro analysis. PBF and cortactin (CTTN) expression was determined in differentiated thyroid cancer and The Cancer Genome Atlas RNA-seq data. PRIMARY OUTCOME MEASURE: Pro-invasive effects of PBF were evaluated by 2D Boyden chamber, 3D organotypic, and proximity ligation assays. RESULTS: Our study identified that PBF and CTTN physically interact and co-localize, and that this occurs at the cell periphery, particularly at the leading edge of migrating cancer cells. Critically, PBF induces potent cellular invasion and migration in thyroid and breast cancer cells, which is entirely abrogated in the absence of CTTN. Importantly, we found that CTTN is over-expressed in differentiated thyroid cancer, particularly in patients with regional lymph node metastasis, which significantly correlates with elevated PBF expression. Mutation of PBF (Y174A) or pharmacological intervention modulates the PBF: CTTN interaction and attenuates the invasive properties of cancer cells. CONCLUSION: Our results demonstrate a unique role for PBF in regulating CTTN function to promote endocrine cell invasion and migration, as well as identify a new targetable interaction to block tumor cell movement.

Active Motor Training Has Long-term Effects on Infants' Object Exploration.

Long-term changes in infants' behavior as a result of active motor training were studied. Thirty-two infants completed three visits to the laboratory. At the first visit, infants were 3 months old and completed an object exploration assessment. Then the experimenter demonstrated the motor training procedures appropriate for the infant's experimental condition, and parents took home custom infant mittens (either sticky or non-sticky) and a bag of lightweight toys to practice with their infants. Over the course of the following 2 weeks, infants participated in 10 sessions of either active (sticky) or passive (non-sticky) mittens training at home with their parents. Infants who participated in active mittens training wore mittens with the palms covered in Velcro, allowing them to pick up and move around small toys. Infants who participated in passive mittens training wore non-sticky mittens, and their parents moved the toys through their visual fields on their behalf. After completing the training, infants returned to the lab for the second visit. At visit two, infants participated in another object exploration assessment as well as a reaching assessment. Parents returned the training materials to the lab at the second visit, and were told not to continue any specific training regimen from this point forward. Two months later, when infants were about 5.5 months of age, they returned to the lab for a third visit. At the third visit, infants completed the same two assessments as during the second visit. The results of this study indicate that infants who participated in active motor training engaged in more sophisticated object exploration when compared to infants who received passive training. These findings are consistent with others in the literature showing that active motor training at 3 months of age facilitates the processes of object exploration and engagement. The current results and others reveal that the effects of early experience can last long after training ceases.

Direct and Absolute Quantification of over 1800 Yeast Proteins via Selected Reaction Monitoring.

Defining intracellular protein concentration is critical in molecular systems biology. Although strategies for determining relative protein changes are available, defining robust absolute values in copies per cell has proven significantly more challenging. Here we present a reference data set quantifying over 1800Saccharomyces cerevisiaeproteins by direct means using protein-specific stable-isotope labeled internal standards and selected reaction monitoring (SRM) mass spectrometry, far exceeding any previous study. This was achieved by careful design of over 100 QconCAT recombinant proteins as standards, defining 1167 proteins in terms of copies per cell and upper limits on a further 668, with robust CVs routinely less than 20%. The selected reaction monitoring-derived proteome is compared with existing quantitative data sets, highlighting the disparities between methodologies. Coupled with a quantification of the transcriptome by RNA-seq taken from the same cells, these data support revised estimates of several fundamental molecular parameters: a total protein count of ∼100 million molecules-per-cell, a median of ∼1000 proteins-per-transcript, and a linear model of protein translation explaining 70% of the variance in translation rate. This work contributes a "gold-standard" reference yeast proteome (including 532 values based on high quality, dual peptide quantification) that can be widely used in systems models and for other comparative studies.