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Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human‐derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation‐related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs. [ABSTRACT FROM AUTHOR]

We investigated the effects of differential and nondifferential reinforcers on divided control by compound‐stimulus dimensions. Six pigeons responded in a delayed matching‐to‐sample procedure in which a blue or yellow sample stimulus flashed on/off at a fast or slow rate, and subjects reported its color or alternation frequency. The dimension to report was unsignaled (Phase 1) or signaled (Phase 2). Correct responses were reinforced with a probability of.70, and the probability of reinforcers for errors varied across conditions. Comparison choice depended on reinforcer ratios for correct and incorrect responding; as the frequency of error reinforcers according to a dimension increased, control (measured by log d) by that dimension decreased and control by the other dimension increased. Davison and Nevin's (1999) model described data when the dimension to report was unsignaled, whereas model fits were poorer when it was signaled, perhaps due to carryover between conditions. We are the first to test this quantitative model of divided control with reinforcers for errors and when the dimension to report is signaled; hence, further research is needed to establish the model's generality. We question whether divided stimulus control is dimensional and suggest it may instead reflect joint control by compound stimuli and reinforcer ratios. [ABSTRACT FROM AUTHOR]

Organisms may sometimes behave as if a contingency exists between behavior and consequences, even if this is not actually the case. Killeen (1978) suggested that such superstition occurs because of factors that bias subjects to behave "superstitiously" rather than because of failures of discrimination. We systematically replicated Killeen's experiment and compared contingency discrimination between different consequences. Six pigeons responded in a matching‐to‐sample procedure in which a response‐independent or response‐dependent stimulus change, food delivery, or blackout occurred. The pigeons reported whether the consequence was response dependent or response independent by choosing between two side keys. Discrimination was strongest after stimulus changes, weaker after blackouts, and weakest after food deliveries. These differences persisted even after additional training, suggesting asymmetries that may reflect differences in the disruptive effects of different consequences on remembering and/or behavioral mnemonics. Importantly, the pigeons were not biased to report response‐dependent consequences unless that response was consistent with locational biases; that is, they behaved "superstitiously" when there was a reason to be biased to do so. These findings corroborate Killeen's and demonstrate that behavior may deviate from contingencies not necessarily because subjects cannot discriminate those contingencies but because they are biased to behave otherwise. [ABSTRACT FROM AUTHOR]

Stimulus overselectivity describes strong control by one stimulus element at the expense of other equally relevant elements. Research suggests that control by underselected stimuli emerges following extinction of the overselected stimulus ("revaluation") and the emergence is larger when overselectivity is greater. We compared such revaluation effects with a control compound or condition in two experiments. Human participants chose between compound S+ and S‐ stimuli. Then, to assess control by compound‐stimulus elements, participants chose between individual elements in a testing phase without feedback. The S+ element chosen most often (the overselected element) underwent revaluation, during which choice of that element was extinguished and choice of a novel element reinforced. Thereafter, participants completed a retesting phase. Revaluation reduced choice of the overselected element. Choice of the underselected element decreased for participants with low overselectivity but increased for participants with high overselectivity. This was not the case for a control compound that did not undergo revaluation (Experiments 1 and 2) or in a control condition in which the overselected element continued to be reinforced during revaluation (Experiment 2). These findings suggest that overselectivity levels may modulate revaluation effects, and they also highlight the importance of the contingency change in postrevaluation changes in stimulus control. [ABSTRACT FROM AUTHOR]

Objective: Blunt trauma patients with potential cervical spine injury are traditionally immobilised in rigid collars. Recently, this has been challenged. The present study's objective was comparison of the rate of patient‐oriented adverse events in stable, alert, low‐risk patients with potential cervical spine injuries immobilised in rigid versus soft collars. Methods: Unblinded, prospective quasi‐randomised clinical trial of neurologically intact, adult, blunt trauma patients assessed as having potential cervical spine injury. Patients were randomised to collar type. All other aspects of care were unchanged. Primary outcome was patient‐reported discomfort related to neck immobilisation by collar type. Secondary outcomes included adverse neurological events, agitation and clinically important cervical spine injuries (clinical trial registration number: ACTRN12621000286842). Results: A total of 137 patients were enrolled: 59 patients allocated to a rigid collar and 78 to a soft collar. Most injuries were from a fall <1 m (54%) or a motor vehicle crash (21.9%). Median neck pain score of collar immobilisation was lower in the soft collar group (3.0 [interquartile range 0–6.1] vs 6.0 [interquartile range 3–8.8], P < 0.001). The proportion of patients with clinician‐identified agitation was lower in the soft collar group (5% vs 17%, P = 0.04). There were four clinically important cervical spine injuries (two in each group). All were treated conservatively. There were no adverse neurological events. Conclusions: Use of soft rather than rigid collar immobilisation for low‐risk blunt trauma patients with potential cervical spine injury is significantly less painful for patients and results in less agitation. A larger study is needed to determine the safety of this approach or whether collars are required at all. [ABSTRACT FROM AUTHOR]

Adoption of technology in the financial services industry has been accelerating in recent years. To assess its contribution to financial inclusion, we develop a novel digital financial inclusion index covering 52 emerging market and developing economies. We find that (i) the adoption of digital financial services has been a key driver of financial inclusion; and (ii) there is wide variation across countries and regions, with the greatest progress recorded in Africa and Asia. Given the accelerated adoption of digital payments during the COVID‐19 pandemic, policies are needed to close the digital divide to ensure continued progress in financial inclusion and safeguard trust in financial services. [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidence suggests that the prevalence of eating disorders among Chinese women is a public health concern. Prior studies have drawn linkages between conflicting cultural values, identity confusion, and eating disorder symptomatology, which may be relevant for understanding the rise of eating disorders amidst China's rapid economic and sociocultural transformation. Here, we explore how women's experiences with traditional eating norms and modernizing norms of femininity may shape their food and body attitudes. Method: Chinese young adult women (N = 34; aged 18–22 years) participated in semi‐structured interviews focusing on experiences with norms surrounding eating and ideal feminine appearance, perceived conflict between these norms, and their responses to perceived conflict. Interviews were conducted via email (n = 27) or via Skype (n = 7). Participants were not asked about past or present diagnoses of eating disorders. Analysis of responses was guided by the principles of thematic analysis. Results: Women reported encounters with cultural eating norms and feminine appearance norms, and described factors that motivated continued or discontinued adherence to these norms. Women reported strategies of conflict resolution, which resulted in different emotional and behavioral outcomes including eating disorder symptoms. Discussion: Women's experiences with norms surrounding eating and appearance indicate the centrality of these encounters in the formation of individual and interpersonal values. Our findings suggest the importance for clinicians to assist clients in exploring the meanings behind internalized attitudes toward food and body, and to help clients balance interpersonal and individual needs. [ABSTRACT FROM AUTHOR]

Stimuli that provide information about likely future reinforcers tend to shift behavior, provided a reliable relation between the stimulus and the reinforcer can be discriminated. Stimuli that are apparently more reliable exert greater control over behavior. We asked how the subjective value (measured in terms of preference) of reinforcers associated with stimuli influences stimulus control. Five pigeons worked on a concurrent chains procedure in which half of all trials ended in a smaller reinforcer sooner, and the other half in a larger reinforcer later. In Signaled trials, the color and flash duration on the keys in the initial link signaled the outcome of the trial. In Conflicting probe trials, the color and the flash duration signaled conflicting information about the outcome of the trial. Choice in Signaled trials shifted toward the signaled outcome, but was never exclusive. In Conflicting probe trials, control was divided idiosyncratically between the 2 stimulus dimensions, but still favored the outcome with the higher subjective value. Thus, stimulus control depends not only on the perceived reliability of stimuli, but also on the subjective value of the outcome. [ABSTRACT FROM AUTHOR]

In concurrent schedules, reinforcers are often followed by a brief period of heightened preference for the just-productive alternative. Such 'preference pulses' may reflect local effects of reinforcers on choice. However, similar pulses may occur after nonreinforced responses, suggesting that pulses after reinforcers are partly unrelated to reinforcer effects. McLean, Grace, Pitts, and Hughes (2014) recommended subtracting preference pulses after responses from preference pulses after reinforcers, to construct residual pulses that represent only reinforcer effects. Thus, a reanalysis of existing choice data is necessary to determine whether changes in choice after reinforcers in previous experiments were actually related to reinforcers. In the present paper, we reanalyzed data from choice experiments in which reinforcers served different functions. We compared local choice, mean visit length, and visit-length distributions after reinforcers and after nonreinforced responses. Our reanalysis demonstrated the utility of McLean et al.'s preference-pulse correction for determining the effects of reinforcers on choice. However, visit analyses revealed that residual pulses may not accurately represent reinforcer effects, and reinforcer effects were clearer in visit analyses than in local-choice analyses. The best way to determine the effects of reinforcers on choice may be to conduct visit analyses in addition to local-choice analyses. [ABSTRACT FROM AUTHOR]

Angiotensin (ANGII) and secretin (SCT) share overlapping, interdependent osmoregulatory functions in brain, where SCT peptide/receptor function is required for ANGII action, yet the molecular basis is unknown. Since receptors for these peptides (AT1aR, SCTR) are coexpressed in osmoregulatory centers, a possible mechanism is formation of a cross-class receptor heterocomplex. Here, we demonstrate such a complex and its functional importance to modulate signaling. Association of AT1aR with SCTR reduced ability of SCT to stimulate cyclic adenosine monophosphate (cAMP), with signaling augmented in presence of ANGII or constitutively active AT1aR. Several transmembrane (TM) peptides of these receptors were able to affect their conformation within complexes, reducing receptor BRET signals. AT1aR TM1 affected only formation and activity of the heterocomplex, without effect on homomers of either receptor, and reduced SCT-stimulated cAMP responses in cells expressing both receptors. This peptide was active in vivo by injection into mouse lateral ventricle, thereby suppressing water-drinking behavior after hyperosmotic shock, similar to SCTR knockouts. This supports the interpretation that active conformation of AT1aR is a key modulator of cAMP responses induced by SCT stimulation of SCTR. The SCTR/AT1aR complex is physiologically important, providing differential signaling to SCT in settings of hyperosmolality or food intake, modulated by differences in levels of ANGII. [ABSTRACT FROM AUTHOR]

The olfactory bulb differs from other brain regions by its use of bidirectional synaptic transmission at dendrodendritic reciprocal synapses. These reciprocal synapses provide tight coupling of inhibitory feedback from granule cell interneurons to mitral cell projection neurons in the accessory olfactory bulb (AOB), at the first stage of vomeronasal processing. It has been proposed that both the mGluR2 agonist DCG-IV and noradrenaline promote mate recognition memory formation by reducing GABAergic feedback on mitral cells. The resultant mitral cell disinhibition is thought to induce a long-lasting enhancement in the gain of inhibitory feedback from granule to mitral cells, which selectively gates the transmission of the learned chemosensory information. However, we found that local infusions of both noradrenaline and DCG-IV failed to disinhibit AOB neural activity in urethane-anaesthetised mice. DCG-IV infusion had similar effects to the GABAA agonist isoguvacine, suggesting that it increased GABAergic inhibition in the AOB rather than reducing it. Noradrenaline infusion into the AOB also failed to disinhibit mitral cells in awake mice despite inducing long-term increases in power of AOB local field potentials, similar to those observed following memory formation. These results suggest that mitral cell disinhibition is not essential for the neural changes in the AOB that underlie mate recognition memory formation in mice. [ABSTRACT FROM AUTHOR]

Glucagon and the glucagon-like peptides (GLP-1 and GLP-2) share a common evolutionary origin and are triplication products of an ancestral glucagon exon. In mammals, a standard scenario is found where only a single proglucagon-derived peptide set exists. However, fish and amphibians have either multiple proglucagon genes or exons that are likely resultant of duplication events. Through phylogenetic analysis and examination of their respective functions, the proglucagon ligand-receptor pairs are believed to have evolved independently before acquiring specificity for one another. This review will provide a comprehensive overview of current knowledge of proglucagon-derived peptides and receptors, with particular focus on fish and amphibian species. [ABSTRACT FROM AUTHOR]

Aim: After carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS) for patients with severe carotid stenosis, an ischaemic event may still happen in up to 9% of patients over a 2 year period. We aimed to investigate whether baseline cerebrovascular reactivity could predict a subsequent ischaemic event after intervention. Methods: A total of 51 patients with severe carotid stenosis (more than 70% stenosis from ultrasonography) and data on cerebrovascular reactivity were reviewed. Thirty-six patients had either CEA or CAS performed and were recruited for analysis. Transcranial Doppler ultrasonography was used to examine the reactivity of the middle cerebral artery to 5% carbon dioxide in oxygen. Normal cerebrovascular reactivity was defined by >1% increase per unit change in end-tidal CO2 in ipsilateral middle cerebral artery velocity in response to 5% carbon dioxide in oxygen. The mean follow-up period was 66 months. Results: Twenty-six patients had symptomatic carotid stenosis and 10 patients had asymptomatic carotid stenosis. There were four subsequent ischaemic events during follow up. None of the nine patients with impaired baseline ipsilateral cerebrovascular reactivity had a subsequent ischaemic event. Conclusion: From our patient cohort, impaired baseline ipsilateral cerebrovascular reactivity before carotid intervention was not predictive of a subsequent ischaemic event. [ABSTRACT FROM AUTHOR]

More than 4000 patients with mild head injury are managed in public hospitals in Hong Kong every year. It is a common belief that mild head injuries do not result in long-term disabilities. We aim to: (i) investigate the disability after mild head injury using objective assessment tools; and (ii) analyse risk factors that contribute to these disability.Patients with a Glasgow Coma Score of 13–15 admitted between January and March 2002 were recruited for study. Their long-term clinical outcome (2 years after initial injury) was prospectively documented with the Glasgow outcome scale– extended (GOSE). Glasgow outcome scale– extended is the primary outcome measure. A GOSE score less than 7 was considered failure to restore to previous working capacity.One hundred and sixty-two patients were recruited, of which 101 were successfully contacted. Two years after injury, 28.7% of the patients scored less than 7 (failure to restore working capacity). Injury on duty was shown to be a significant risk factor for predicting long-term disability (P = 0.03). Radiological abnormality was not a significant predictor in long-term disabilities.Incidence of long-term disability after mild head injury is common among the local working population in Hong Kong and should not be overlooked. Further research is needed to quantify the disability and to identify possible risk factors. [ABSTRACT FROM AUTHOR]

Aim: To investigate the timing and degree of recovery of isolated third nerve palsy due to unruptured posterior communicating artery aneurysm among a Chinese population. Methods: A total of seven eligible patients were studied during a 4-year period by retrospective review. The degree of recovery and time to achieve recovery after presentation were the main outcome measures. Results: There were seven patients with isolated third nerve palsy related to posterior communicating artery aneurysm. After treatment the median recovery time from the initial symptoms was 14 weeks, ranging from 1 to 60 weeks. Two patients (29%) in this group had mild residual symptoms. Conclusion: The present study demonstrated that in patients with isolated third nerve palsy related to posterior communicating artery aneurysm, recovery occurred within the first year and the prognosis of recovery was good. [ABSTRACT FROM AUTHOR]