Allocation Bias Research Articles

Coronoid tip fractures in terrible triad injuries can be safely treated without fixation.

The optimal treatment of terrible triad injuries of the elbow (TTI) remains topic of ongoing discussion. The aim of this study was to determine whether different treatment strategies for coronoid tip fractures in terrible triad injuries influences the clinical and radiological results in a mid-term follow-up. A total of 62 patients with surgical treatment of a TTI including a coronoid tip fracture (37 women, 25 men; mean age, 51years) were available for follow-up assessment after an average of 4.2years (range 24-110months). Thirteen patients had O'Driscoll 1.1 and 49 O'Driscoll 1.2 coronoid fractures, of which 26 were treated with and 36 without fixation. Range of motion, the Mayo Elbow Performance Score (MEPS), Oxford Elbow Score (OES), and Disabilities of the Arm, Shoulder and Hand (DASH) score as well as grip strength were evaluated. Radiographs were analyzed for all participants. No significant benefit in outcome variables could be detected between patients, whose coronoid had been fixed, compared to patients without fixation of the coronoid. In the coronoid fixation group, patients had mean outcome scores of 81.5 ± SD 19.1 (range 35-100) for MEPS, 31.0 ± SD 12.5 (range 11-48) for OES and 27.7 ± SD 23 (range 0-61) for DASH score, while in the no-fixation group, mean MEPS was 90.8 ± SD 16.5 (range 40-100), mean OES was 39.0 ± SD 10.4 (range 16-48) and mean DASH score was 14.5 ± SD 19.9 (range 0-48). Mean range of motion was 116° ± SD 21° (range 85-140°) versus 124° ± SD 24° (range 80-150°) in extension-flexion and 158° ± SD 23° (range 70-180°) versus 165° ± SD 12° (range 85-180°) in pronation-supination. Overall complication rate was 43.5% and revision rate was 24.2%, with no significant differences between both groups. Suboptimal results were more frequently seen in patients who had degenerative or heterotopic changes on their latest radiograph. Sufficient elbow stability and good outcomes can be achieved in most patients with TTI and coronoid tip fractures. Although some bias in treatment allocation and group heterogeneity cannot be completely omitted, our analysis detected no significant benefit in outcome when the coronoid tip fracture has been fixed compared to patients with non-fixed coronoid tip. Therefore, we would suggest a no-fixation approach for coronoid tip fractures as primary treatment in TTI of the elbow. Level III, retrospective comparative study.

Eye-tracking indices of attention allocation and attention bias variability are differently related to trauma exposure and PTSD

Amplified attention allocation to negative information in one’s environment has been implicated in posttraumatic stress disorder (PTSD). Attention bias variability (ABV), the magnitude of attention fluctuation between negative and neutral cues, has also been found to be elevated in PTSD. While eye-tracking methodology has been used in research on attention allocation in PTSD, ABV was only explored using manual reaction-time-based indices. Thirty-seven participants with PTSD, 34 trauma-exposed healthy controls (TEHC), and 30 non-exposed healthy controls (HC) completed an eye-tracking free-viewing task in which matrices comprised of neutral and negatively-valenced faces were presented. Threat-related attention allocation was calculated as the proportion of dwell time (DT%) on negatively-valenced faces. Eye-tracking-based ABV was calculated as the standard deviation of DT% across matrices. DT% on negatively-valenced faces was greater in participants with PTSD compared to both TEHC (p = .036, d = 0.50) and HC (p < .001, d = 1.03), with TEHCs showing a greater attentional bias compared to HCs (p = .001, d = 0.84). Controlling for average fixation duration, ABV was higher in both the PTSD and TEHC groups relative to the HC group (p = .004, d = 0.40), with no difference between the two trauma-exposed groups. Biased attention allocation toward negative social information is related to PTSD pathology, whereas elevated ABV measured with eye-tracking appear to be related to trauma-exposure per-se.

Impact of biased technological progress on the total factor productivity of China's manufacturing industry: The driver of sustainable economic growth

Sustainable economic growth relies on an increase in total factor productivity (TFP). To upgrade the core competitiveness and support the sustainable growth and high-quality development of China's economy, ascending TFP in China's manufacturing industry counts. This study analysed the impact of biased technological progress on TFP, which was estimated by using the relevant data of 27 subsectors of China's manufacturing industry from 1980 to 2019. The results revealed that from the early industrialisation period (1980–2000) to the mid-industrialisation period (2001–2012) and then to the middle and late industrialisation period (2013–2019), the mean value of TFP in China's manufacturing industry grew from 0.291 to 0.394 and then to 0.555, embodying a continuously upwards advancing tendency. Technological progress was capital biased from 1981 to 2011 and labour biased during the rest of the sample period. In addition, its direction was heterogeneous among various industries. To some extent, the growth of TFP has been hindered by biased technological progress and factor allocation. The per unit increase in them has led to 1.495 and 1.017 unit decreases in the TFP. Upon examining the factor efficiency and the factor structure, we found that the estimated coefficients of biased technological progress dropped to −1.516 and −1.719, preventing TFP from growing to a greater extent. Consequently, there is room for their optimisation in China's manufacturing industry.

Anakinra for Refractory Cytokine Release Syndrome or Immune Effector Cell-Associated Neurotoxicity Syndrome after Chimeric Antigen Receptor T Cell Therapy

Chimeric antigen receptor-engineered (CAR)-T cell therapy remains limited by significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The optimal management of severe and/or refractory CRS/ICANS remains ill-defined. Anakinra has emerged as a promising agent based on preclinical data, but its safety and efficacy in CAR-T therapy recipients are unknown. The primary objective of this study was to evaluate the safety of anakinra to treat refractory CRS and ICANS after CAR-T therapy. The secondary objective was to evaluate the impact of key treatment-, patient-, and disease-related variables on the time to CRS/ICANS resolution and treatment-related mortality (TRM). We retrospectively analyzed the outcomes of 43 patients with B cell or plasma cell malignancies treated with anakinra for refractory CRS or ICANS at 9 institutions in the United States and Spain between 2019 and 2022. Cause-specific Cox regression was used to account for competing risks. Multivariable cause-specific Cox regression was used to estimate the effect of anakinra dose on outcomes while minimizing treatment allocation bias by including age, CAR-T product, prelymphodepletion (pre-LD) ferritin, and performance status. Indications for anakinra treatment were grade ≥2 ICANS with worsening or lack of symptom improvement despite treatment with high-dose corticosteroids (n=40) and grade ≥2 CRS with worsening symptoms despite treatment with tocilizumab (n=3). Anakinra treatment was feasible and safe; discontinuation of therapy because of anakinra-related side effects was reported in only 3 patients (7%). The overall response rate (ORR) to CAR-T therapy was 77%. The cumulative incidence of TRM in the whole cohort was 7% (95% confidence interval [CI], 2% to 17%) at 28 days and 23% (95% CI, 11% to 38%) at 60 days after CAR-T infusion. The cumulative incidence of TRM at day 28 after initiation of anakinra therapy was 0% in the high-dose (>200 mg/day i.v.) recipient group and 47% (95% CI, 20% to 70%) in the low-dose (100 to 200 mg/day s.c. or i.v.) recipient group. The median cumulative incidence of CRS/ICANS resolution from the time of anakinra initiation was 7 days in the high-dose group and was not reached in the low-dose group, owing to the high TRM in this group. Univariate Cox modeling suggested a shorter time to CRS/ICANS resolution in the high-dose recipients (hazard ratio [HR], 2.19; 95% CI, .94 to 5.12; P=.069). In a multivariable Cox model for TRM including age, CAR-T product, pre-LD ferritin level, and pre-LD Karnofsky Performance Status (KPS), higher anakinra dose remained associated with lower TRM (HR, .41 per 1 mg/kg/day increase; 95% CI, .17 to .96; P=.039. The sole factor independently associated with time to CRS/ICANS resolution in a multivariable Cox model including age, CAR-T product, pre-LD ferritin and anakinra dose was higher pre-LD KPS (HR, 1.05 per 10% increase; 95% CI, 1.01 to 1.09; P=.02). Anakinra treatment for refractory CRS or ICANS was safe at doses up to 12 mg/kg/day i.v. We observed an ORR of 77% after CAR-T therapy despite anakinra treatment, suggesting a limited impact of anakinra on CAR-T efficacy. Higher anakinra dose may be associated with faster CRS/ICANS resolution and was independently associated with lower TRM. Prospective comparative studies are needed to confirm our findings.

Disastrous Discretion: Political Bias in Relief Allocation Varies Substantially with Disaster Severity

Abstract Allocation decisions are vulnerable to political influence, but it is unclear in which situations politicians use their discretionary power in a partisan manner. We analyze the allocation of presidential disaster declarations in the United States, exploiting the spatiotemporal randomness of all hurricane strikes from 1965-2018 along with changes in political alignment. We show that decisions are unbiased when disasters are either very strong or weak. Only after medium-intensity hurricanes do areas governed by presidents' co-partisans receive up to twice as many declarations. This hump-shaped political bias explains 8.3 percent of overall relief spending, totaling about USD 400 million per year.

Intestinal Immune Deficiency and Juvenile Hormone Signaling Mediate a Metabolic Trade-off in Adult Drosophila Females

A trade-off hypothesis pertains to the biased allocation of limited resources between two of the most important fitness traits, reproduction and survival to infection. This quid pro quo manifests itself within animals prioritizing their energetic needs according to genetic circuits balancing metabolism, germline activity and immune response. Key evidence supporting this hypothesis includes dipteran fecundity being compromised by systemic immunity, and female systemic immunity being compromised by mating. Here, we reveal a local trade-off taking place in the female Drosophila midgut upon immune challenge. Genetic manipulation of intestinal motility, permeability, regeneration and three key midgut immune pathways provides evidence of an antagonism between specific aspects of intestinal defense and fecundity. That is, juvenile hormone (JH)-controlled egg laying, lipid droplet utilization and insulin receptor expression are specifically compromised by the immune deficiency (Imd) and the dual oxidase (Duox) signaling in the midgut epithelium. Moreover, antimicrobial peptide (AMP) expression under the control of the Imd pathway is inhibited upon mating and JH signaling in the midgut. Local JH signaling is further implicated in midgut dysplasia, inducing stem cell-like clusters and gut permeability. Thus, midgut JH signaling compromises host defense to infection by reducing Imd-controlled AMP expression and by inducing dysplasia, while midgut signaling through the Imd and Duox pathways compromises JH-guided metabolism and fecundity.

Gender Disparities in Critical Care Procedure Training of Internal Medicine Residents.

Procedural training is a required competency in internal medicine (IM) residency, yet limited data exist on residents' experience of procedural training. We sought to understand how gender impacts access to procedural training among IM residents. A mixed-methods, explanatory sequential study was performed. Procedure volume for IM residents between 2016 and 2020 was assessed at two large academic residencies (Program A and Program B: 399 residents and 4,020 procedures). Procedural rates and actual versus expected procedure volume by gender were compared, with separate analyses by clinical environment (intensive care unit [ICU] or structured procedural service). Semistructured gender-congruent focus groups were conducted. Topics included identity formation as a proceduralist and the resident procedural learning experience, including perceived gender bias in procedure allocation. Compared with men, women residents performed disproportionately fewer ICU procedures per month at Program A (1.4 vs. 2.7; P < 0.05) but not at Program B (0.36 vs. 0.54; P = 0.23). At Program A, women performed only 47% of ICU procedures, significantly fewer than the 54% they were expected to perform on the basis of their time on ICU rotations (P < 0.001). For equal gender distribution of procedural volume at Program A, 11% of the procedures performed by men would have needed to have been performed by women instead. Gender was not associated with differences in the Program A structured procedural service (53% observed vs. 52% expected; P = 0.935), Program B structured procedural service (40% observed vs. 43% expected; P = 0.174), or in Program B ICUs (33% observed vs. 34% expected; P = 0.656). Focus group analysis identified that women from both residencies perceived that assertiveness was required for procedural training in unstructured learning environments. Residents felt that gender influenced access to procedural opportunities, ability to self-advocate for procedural experience, identity formation as a proceduralist, and confidence in acquiring procedural skills. Gender disparities in access to procedural training during ICU rotations were seen at one institution but not another. There were ubiquitous perceptions that assertiveness was important to access procedural opportunities. We hypothesize that structured allocation of procedures would mitigate disparities by allowing all residents to access procedural training regardless of self-advocacy. Residency programs should adopt structured procedural training programs to counteract inequities.

Aging a Decade in a Day: Age Cutoff Bias in Adjuvant Therapy Allocation for Early-Stage Breast Cancer

Physicians may expedite interpretation of data presented as a continuous variable by binning the data into "high" and "low" subgroups (cutoff heuristic). Use of this cognitive shortcut with age may lead to fewer nuanced or inappropriate decisions. We hypothesized an age cutoff heuristic may lead to non-evidence-based adjuvant treatment allocation among patients with early-stage breast cancer. Two cohorts with strong indications for adjuvant treatment regardless of age that underwent lumpectomy for early-stage breast cancer between 2004 and 2017 were identified in the National Cancer Database. Cohort 1 had higher-risk features (estrogen receptor negative, endocrine therapy not planned, final margins positive, or size >3 cm; n=160,990) and was appropriate for radiation. Cohort 2 had hormone receptor positivity with tumors >5 mm (n=394,946) and was appropriate for endocrine therapy. Multivariable logistic regressions with odds ratios (ORs) and 99.8% confidence intervals (CIs) were performed to determine whether any single year-over-year age difference was independently associated with a difference in likelihood of adjuvant therapy recommendation. In cohort 1, radiation recommendation decreased sharply at age 70, ranging from 90% to 92% between the ages of 50 and 69 years to 81% for those aged 70 years. Multivariable logistic regressions showed year-over-year age difference was an independent predictor for adjuvant radiation recommendation at only age 70 versus 69 (OR, 0.47; CI, 0.39-0.57; P < .001). For cohort 2, endocrine therapy recommendation showed a small decline at age 70, and year-over-year age difference was a predictor of endocrine therapy recommendation at only age 70 versus 69 (OR, 0.86; CI, 0.74-0.99; P=.001). We observed a unique decline in appropriate adjuvant therapy recommendation between ages 69 and 70. This suggests use of an age cutoff heuristic to process patient age in this population as a categorical, binary variable. This is a previously undescribed phenomenon in early-stage breast cancer.

Gender and sex bias in COVID-19 epidemiological data through the lens of causality

The COVID-19 pandemic has spurred a large amount of experimental and observational studies reporting clear correlation between the risk of developing severe COVID-19 (or dying from it) and whether the individual is male or female. This paper is an attempt to explain the supposed male vulnerability to COVID-19 using a causal approach. We proceed by identifying a set of confounding and mediating factors, based on the review of epidemiological literature and analysis of sex-dis-aggregated data. Those factors are then taken into consideration to produce explainable and fair prediction and decision models from observational data. The paper outlines how non-causal models can motivate discriminatory policies such as biased allocation of the limited resources in intensive care units (ICUs). The objective is to anticipate and avoid disparate impact and discrimination, by considering causal knowledge and causal-based techniques to compliment the collection and analysis of observational big-data. The hope is to contribute to more careful use of health related information access systems for developing fair and robust predictive models.

Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: A multicenter prospective study

ObjectiveThis multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. MethodsSurgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-μm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. ResultsA total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961–0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819–0.973) and 0.989 (95% CI: 0.973–0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. ConclusionsThe OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.

Machine Translation and Gender biases in video game localisation: a corpus-based analysis

The video game industry has been a historically gender-biased terrain due to a higher number of male protagonists and hypersexualised representations [Dietz, 1998; Downs &amp; Smith, 2010; Lynch et al., 2016]. Nowadays, echoing the debate on inclusive language, companies attempt to erase gender disparity by introducing main female characters as well as non-binary characters. From a technological point of view, even though recent studies show that Machine Translation remains largely unadopted by individual video game localisers [Rivas Ginel, 2021], multilanguage vendors are willing to invest in these tools to reduce costs [LIND, 2020]. However, the predominance of the masculine in Natural Language Processing and Machine Learning has created allocation and representation biases in Neural Machine Translation [Crawford, 2017].This paper aims to analyse the percentage of gender bias resulting from the use of Google Translate, DeepL, and SmartCat when translating in-game raw content from English into French. The games DeltaRune, The Devil's Womb and The Faces of the Forest were chosen due to the presence of non-binary characters, non-sexualized characters, and female protagonists. We compared the results in order to recount and analyse the differences between these tools' output when in terms of errors related to gender. To this end, we created a parallel corpus to compare source documents and all the translations to visualise the semantic and grammatical directions of the words embeddings [Zhou; Shi; Zhao and al, 2019] and extracted the collocations and concordance lines that represented gender identity by analysing the patterns in the source language.

Laser therapy for retinopathy in sickle cell disease.

Laser therapy for retinopathy in sickle cell disease.

Distributive justice criteria and social categorization processes predict healthcare allocation bias.

Drawing on theories of distributive justice and intergroup discrimination, we examined how much distributive justice criterion and racial group membership contribute to bias in healthcare allocation decisions, by testing a theoretical model that specifies perceived stereotypicality and individual responsibility as a serial mediation process in the relationship between disease's contraction controllability (controllable vs. non-controllable) and bias in medical decision-making. White Portuguese medical students (N=213) participated in an online experimental study conducted in two phases. In phase 1, we manipulated the cause of disease contagion and the salience of patient's racial categorization, and measured the stereotypicality of behaviour. In phase 2, we assessed perceived responsibility and likelihood of recommending medical treatment. Controllable (vs. non-controllable) contraction behaviours in phase 1 were perceived as more stereotypic. As a spillover effect, more stereotypical behaviours in phase 1 predicted more patient's responsibility for their disease in phase 2. Importantly, controllable behaviours of disease contraction in phase 1 negatively affected recommendations for medical treatment in phase 2; and this negative effect was serially mediated by the stereotypicality of behaviour and patient responsibility. Furthermore, patients' skin colour moderated this process, meaning that perceptions of controllable behaviour as more stereotypic were stronger for Black than for White patients. This research shows how stereotyping and social categorization bias allocation decisions through the patient's level of responsibility in decision-making processes. The findings are discussed in light of principles of distributive justice and the literature on intergroup relations with respect to racial disparities in health care.

Comparison of outcomes across low-intensity psychological interventions for depression and anxiety within a stepped-care setting: A naturalistic cohort study using propensity score modelling.

Low-intensity interventions for common mental disorders (CMD) address issues such as clinician shortages and barriers to accessing care. However, there is a lack of research into their comparative effectiveness in routine care. We aimed to compare treatment effects of three such interventions, utilizing four years' worth of routine clinical data. Users completing a course of guided self-help bibliotherapy (GSH), internet-delivered cognitive behavioural therapy (iCBT) or psychoeducational group therapy (PGT) from a stepped-care service within the NHS in England were included. Propensity score models (stratification and weighting) were used to control for allocation bias and determine average treatment effect (ATE) between the interventions. 21,215 users comprised the study sample (GSH=12,896, iCBT=6862, PGT=1457). Adherence-to-treatment rates were higher in iCBT. All interventions showed significant improvements in depression (PHQ-9), anxiety (GAD-7) and functioning (WSAS) scores, with largest effect sizes for iCBT. Both propensity score models showed a significant ATE in favour of iCBT versus GSH and PGT, and in favour of GSH versus PGT. Discernible differences in effectiveness were seen for iCBT in comparison with GSH and PGT. Given variance in delivery mode and human resources between different low-intensity interventions, building on these findings would be valuable for future service provision and policy decision making.

The critical behavior of Hegselmann–Krause opinion model with smart agents

The Hegselmann–Krause (HK) model allows one to characterize the continuous change of agent opinions with the bounded confidence threshold ɛ. To consider the heterogeneity of agents in characteristics, we study the HK model on homogeneous and heterogeneous networks by introducing a kind of smart agent. Different from the averaging rule in opinion update of HK model, smart agents will consider, in updating their opinions, the environmental influence following the fact that the agent behavior is often coupled with environmental changes. The environment is characterized by a parameter that represents the biased resource allocation between different cliques. We focus on the critical behavior of the underlying system. A phase transition point separating a complete consensus from the coexistence of different opinions is identified, which occurs at a critical value ɛc for the bounded confidence threshold. We state analytically that ɛc can take only one of two possible values, depending on the behavior of the average degree ka of a social graph, when agents are homogeneous in characteristics. Results also suggest that the phase transition point weakly depends on the network structure but is strongly correlated with the fraction of smart agents and the environmental parameter. We finally establish the finite size scaling law that stresses the role that the system size has in the underlying opinion dynamics. Meanwhile, introducing smart agents does not change the functional dependence between the time to reach a complete consensus and the system size. However, it can drive a complete consensus to be reached faster, for homogeneous networks that are far from the mean field limit.

Do Hegemonic-Party Regimes Reward or Punish Voters? A Tale of Distributive Politics in Tanzania

Does resource allocation by the central government to local governments in Tanzania favour opposition or the ruling party's strongholds? The literature advances two opposing theories – electoral competition and hegemonic party hypotheses. We use unique data on fiscal transfers and human resource allocations to investigate the effect of electoral support on government allocations. Contrary to the two hypotheses, we find no political bias in fiscal resources transferred to local governments. Similarly, we find no strong evidence to suggest any political bias in human resource allocation. On the whole, neither does the evidence confirm nor conclusively disconfirm the two hypotheses. The findings imply that hegemonic-parties do not necessarily opt for a discriminative strategy in intergovernmental resource allocations even after facing a threatening opposition. Flexibility in autocratic menu and the path dependence of government's social policy are likely to explain this kind of hegemonic party's allocative behaviour.

Abstract 10874: Predictors of Prehospital Opiate Use in Patients With ST Elevation Myocardial Infarction: Results From a Nationwide Database

Introduction: Opiates are traditionally used in STEMI patients to relieve pain, decrease pulmonary congestion, and anxiety. Yet, according to in vitro measurements, they delay and diminish the effect of all currently used oral platelet P2Y12 receptor antagonists. To be able to draw causal conclusions on the potential effects of opiates on clinical outcomes using real-world registries, the bias in treatment allocation may be minimized by propensity score methods. Therefore, we constructed a simple model of prehospital opiate administration using the database of the National Ambulance Service. Methods: We analyzed data of 10,139 subjects who were diagnosed with STEMI within 24 hours from symptom onset between November 2018 and June 2021. Patients with unsuccessful out-of-hospital CPR were excluded. Opiates were applied in 3,992 cases (39.4%). Besides onset-to-door time and need for CPR due to OHCA, basic demographic data like age and sex were studied as candidate predictors using logistic regression. Non-linearity of the continuous predictors was assessed by restricted cubic splines. Relative importance of the predictors was characterized by the Akaike Information Criterion (AIC). Results: Overall model fit was good: likelihood ratio chi-square=610.40, d.f.=10, p&lt;0.0001. Opiate use was strongly associated with onset-to-door-time (p&lt;0.0001, AIC=333.83) and Wald testing for linearity suggested a non-linear relationship (p&lt;0.0001) with the highest odds at about 120 minutes. Similarly, it was also highly (p&lt;0.0001, AIC=193.78) and non-linearly (p&lt;0.0001) related to age with an inverted U-shaped curve. Moreover, it was negatively dependent on the need for CPR (p=0.0019, AIC=7.64) and unrelated to the sex of the patient (p=0.15, AIC=0.09). Conclusion: Our propensity score model may help to evaluate the role of opiate administration on clinical outcomes of STEMI patients and underscores the importance of non-linear modeling of continuous predictors.

Unbalanced development and progressive repair in human early mosaic and chimeric embryos

With the advancement of genetics and genetic diagnosis, more and more human mosaics and chimeras and even unprecedented type of them have been identified. Especially in the era of universal prenatal screening, human mosaics and chimeras have often been revealed in the embryonic and fetal period with high accuracy. Although mosaicism and chimerism are abnormal in theory, some of them have no detectable effect on embryonic, fetal and postnatal growth and development and adulthood life, which increases difficulties being assessed during genetic counseling. In addition, the following intriguing observations on human mosaicism and chimerism are frequently reported. Continuous prenatal diagnoses indicate that the degree of fetal mosaicism is reduced in some subjects; Mosaicism and chimerism distribute differentially among tissues and organs of an individual; Cells with chromosomal abnormality gradually decrease or even disappear after birth, and are eventually replaced by normal cells. However, to our knowledge, we do not understand how these mosaicisaic and chimerisic phenomenon occur. Here, we propose a hypothesis of unbalanced development and progressive repair to elucidate the underlying mechanisms of these unique mosaic and chimeric phenomenon. The hypothesis is that unbalanced development and progressive repair of human mosaicism and chimerism are achieved by selective pressure and genetic control during development, clonal depletion associated with distinct apoptosis or differentiation potential and heterogoneic division and biased allocation. If this hypothesis is proven, these proposed mechanisms are of great clinical significance in the diagnosis and management of embryonic and fetal mosaicism or chimerism.

Stifled from the start: biased allocation of developmental opportunities and the underrepresentation of lesbian women and gay men in leadership

PurposeThe goal of this study was to help explain the underrepresentation of lesbian women and gay men (LG) in senior leadership positions by examining bias in the allocation of developmental opportunities (sponsorship/coaching and challenging work assignments). It further sought to test stigma-by-association as one reason for the biased allocation of developmental opportunities.Design/methodology/approachAn online experimental vignette study (N = 273) using a 2 (target gender: male vs female) by 2 (sexual orientation: LG vs heterosexual) design was conducted.FindingsLG workers were less likely to be allocated developmental opportunities than heterosexual workers overall and relative to their same-sex heterosexual counterparts. Further, lesbian women were least likely to be allocated developmental opportunities. These effects also operated indirectly via participants concerns about stigma-by-association.Originality/valueSexual orientation and gender identity minority workers remain underrepresented in senior leadership positions and oftentimes despite having better objective qualifications. Research has begun examining bias in leader selection. This study, however, directs attention to the biased allocation of developmental opportunities which make one competitive for senior leadership positions and occur prior to leader selection. In doing so, the authors provide a baseline understanding of an important reason why LG might be underrepresented in leadership positions.

Effects of transcranial direct current stimulation on neural activity and functional connectivity during fear extinction

Background/ObjectiveAnxiety disorders are highly prevalent and negatively impact daily functioning and quality of life. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), especially in the right hemisphere impacts extinction learning; however, the underlying neural mechanisms are elusive. Therefore, we aimed to investigate the effects of cathodal tDCS stimulation to the right dlPFC on neural activity and connectivity patterns during delayed fear extinction in healthy participants. MethodsWe conducted a two-day fear conditioning and extinction procedure. On the first day, we collected fear-related self-reports, clinical questionnaires, and skin conductance responses during fear acquisition. On the second day, participants in the tDCS group (n = 16) received 20-min offline tDCS before fMRI and then completed the fear extinction session during fMRI. Participants in the control group (n = 18) skipped tDCS and directly underwent fMRI to complete the fear extinction procedure. Whole-brain searchlight classification and resting-state functional connectivity analyses were performed. ResultsWhole-brain searchlight classification during fear extinction showed higher classification accuracy of threat and safe cues in the left anterior dorsal and ventral insulae and hippocampus in the tDCS group than in the control group. Functional connectivity derived from the insula with the dlPFC, ventromedial prefrontal cortex, and inferior parietal lobule was increased after tDCS. ConclusiontDCS over the right dlPFC may function as a primer for information exchange among distally connected areas, thereby increasing stimulus discrimination. The current study did not include a sham group, and one participant of the control group was not randomized. Therefore, to address potential allocation bias, findings should be confirmed in the future with a fully randomized and sham controlled study.