Unexpected Gain Research Articles

'We don't have the answers': What do we know about the experiences of psychological professionals providing virtual psychological support to people with intellectual disabilities during the COVID-19 pandemic?

Government restrictions enforced globally in response to COVID-19 necessitated changes to the delivery of mental health services, with many psychology professionals (PPs) forced to transfer their face-to-face practice to virtual means (telephone/video therapy) overnight. This review explores what is known about the experiences of PPs providing psychological support to people with intellectual disabilities (PWID) during the pandemic. Literature was systematically searched and 11 papers were identified, critically appraised and thematically synthesised. Four themes were synthesised from findings: (1) 'Impact at Service Level', (2) 'The Emotional Impact on PPs', (3) 'The Limitations of Virtual Support', (4) 'Unexpected Gains'. This review highlights the challenges and positives in experiences of PPs, whilst acknowledging the inequalities experienced by PWID. It is hoped that the findings can be used to aid education and training, and inform future practice and policy. Future research is recommended.

Deletion induced splicing in RIC3 drives nicotinic acetylcholine receptor regulation with implications for endoplasmic reticulum stress in human astrocytes.

Nicotinic acetylcholine receptor (nAChR) dysregulation in astrocytes is reported in neurodegenerative disorders. Modulation of nAChRs through agonists confers protection to astrocytes from stress but regulation of chaperones involved in proteostasis with pathological implications is unclear. Resistance to inhibitors of cholinesterase 3 (RIC3), a potential chaperone of nAChRs is poorly studied in humans. We characterized RIC3 in astrocytes derived from an isogenic wild-type and Cas9 edited "del" human iPSC line harboring a 25 bp homozygous deletion in exon2. Altered RIC3 transcript ratio due to deletion induced splicing and an unexpected gain of α7nAChR expression were observed in "del" astrocytes. Transcriptome analysis showed higher expression of neurotransmitter/G-protein coupled receptors mediated by cAMP and calcium/calmodulin-dependent kinase signaling with increased cytokines/glutamate secretion. Functional implications examined using tunicamycin induced ER stress in wild-type astrocyte stress model showed cell cycle arrest, RIC3 upregulation, reduction in α7nAChR membrane levels but increased α4nAChR membrane expression. Conversely, tunicamycin-treated "del" astrocytes showed a comparatively higher α4nAChR membrane expression and upsurged cAMP signaling. Furthermore, reduced expression of stress markers CHOP, phospho-PERK and lowered XBP1 splicing in western blot and qPCR, validated by proteome-based pathway analysis indicated lowered disease severity. Findings indicate (i) a complex RNA regulatory mechanism via exonic deletion induced splicing; (ii) RIC-3 as a disordered protein having contrasting effects on co-expressed nAChR subtypes under basal/stress conditions; and (iii) RIC3 as a potential drug target against ER stress in astrocytes for neurodegenerative/nicotine-related brain disorders. Cellular rescue mechanism through deletion induced exon skipping may encourage ASO-based therapies for tauopathies.

Altruism and the Link to Pro-social Pandemic Behavior.

In the Corona pandemic, especially in the phase before vaccines were available, people's risk of infection with COVID-19 was dependent on the adherence to pandemic behaviors (e. g., wearing masks) of others around them. To explore whether altruistic individuals are more likely to engage in pro-social behaviors to protect others during the pandemic, we use data from the European COVID Survey (ECOS). The data was collected in September 2020 and consisted of a representative sample from seven European countries (N = 7,025). Altruism was measured as a deviation from purely self-interested behavior by asking respondents how much they would be willing to donate from an unexpected gain to the equivalent of 1000€. Respondents who were willing to donate more than 0 Euros (68.7%) were treated as altruistic; on average, respondents were willing to donate 11.7% (SD 17.9) of the gain. Controlling for country, sociodemographics, general risk aversion and COVID-specific risk aversion, we find that individuals classified as altruistic were more likely to behave pro-socially. More specifically, we find that altruistic respondents were more likely to wait at home for test results and wear a mask where it is recommended. They would also stay about 1 day longer under quarantine without symptoms after visiting a high-risk country and were less likely to go to a supermarket with COVID symptoms. We find no significant effect for wearing a mask in places where it is mandatory and for inviting more than six people into the house. Furthermore, we find that the subjective risk assessment of COVID-19 also plays a role in these behaviors. Our results support evidence from the literature that suggests that adherence to pro-social pandemic behaviors may be increased if public health officials emphasize the altruistic nature of these behaviors.

A qualitative examination of the impact of the COVID-19 pandemic on children and adolescents with autism and their parents

BackgroundThe unprecedented challenges introduced by the Coronavirus disease 2019 (COVID-19) pandemic may be amplified for children with autism spectrum disorder (ASD) and their families. AimsThe current study aimed to describe the experiences of children with ASD and their families during the pandemic and to identify the needs of this community during emergency situations. Methods and proceduresParticipants were 122 parents of 122 children and adolescents (aged 3–18 years; one parent per family participated) with ASD living in Arizona, USA who participated in the first time point (July/August 2020) of a larger longitudinal survey study. A qualitative approach based in grounded theory methodology was used to analyze six open-ended survey questions. Outcomes and resultsThe resulting conceptual model included a core category, Longing for Stability, and four main categories: Public Health Measures Yielding New Challenges and Unexpected Gains, Experiencing Abrupt Changes across Developmental Domains, Changing Family Dynamics, and Protective Factors. ConclusionsFindings add to limited research examining whether, and how, emergency events uniquely impact the ASD community, identifying potential methods by which services can be proactively adapted to best support the needs of children with ASD.

The Virus and the Environment: The Problem of Sustaining Unexpected Gains

The coronavirus pandemic has had some unexpected benign effects (including a large drop in air pollution and levels of nitrogen oxides in UK and elsewhere, and a smaller drop in global carbon emissions), which raises the problem of how to sustain and build on these unexpected gains. These gains could easily be lost when economies and road transport return to something like their previous condition. But if governments and industries are inspired to reduce automobile emissions to match the levels of the spring of 2020, gains such as these could become recurrent, and many more lives could be saved. Further, if (with greater effort) carbon emissions could remain reduced, then future generations could be saved from sea-level rise, extreme weather events, and even from the spread of tropical diseases. Such a prevention of disease would be an ironic but welcome gain from a pandemic.

Performing the Sea: Fortune, Risk, and Audience Engagement inPericles

Performing the Sea: Fortune, Risk, and Audience Engagement in<i>Pericles</i>

Disappointment or unexpected gain? A survey-based study of the motives and outcomes of inter-municipal cooperation in Poland

Abstract Based on a survey of inter-municipal unions (IMUs) and inter-municipal companies (IMComs) in Poland, this article identifies the most common motives for launching inter-municipal cooperation and the most frequently reported outcomes. The declared motives are compared with the perceived outcomes, with a particular focus on mismatch situations: disappointments (when the expected gain was not realised) and unexpected outcomes (when the reported outcomes exceeded initial expectations). The research shows that the latter are reported more frequently than the former. The most frequently indicated motives for cooperation were related to financial benefits and included cost reduction and applying for additional funding. The “defensive” motive of IMC – cooperation to maintain the status quo – is practically absent. The data also suggests that cooperation can be perceived as “a value in its own right”.

Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape

Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear. Here, we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify a disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.

Event-Related Potentials Are Associated With Unexpected Gain and Loss: Using a Gambling Paradigm.

Previous neuroimaging studies have described altered activity in brain areas associated with reward processing following reward or punishment. This study examines the extent to which feedback-based experience of gain and loss is associated with electrophysiological correlates. Twenty-nine healthy participants used a gambling task that focused on actual nonpredictable gains and losses. During the task, an electroencephalography recording was performed in order to assess reward processing. Event-related potentials were analyzed when participants were receiving gain/loss feedback. Event-related potentials revealed higher feedback-related negativity for both overall gain and loss compared with a neutral condition in fronto-centro-parietal electrodes. P3 potentials were significantly increased for high gains/losses compared to neutral and small gains/losses. These results indicate that the paradigm is suitable to evoke specific patterns of reward-related electrophysiological responses. The wavelet analysis showed that electroencephalography frequency variations depended on the amount of gains/losses. This gambling paradigm is appropriate to measure aspects of feedback processing and could help analyze disease-specific alterations of the reward system in patients.

On the effect of stress state on the failure limits of hole-flanged parts formed by SPIF

Single Point Incremental Forming (SPIF) is a novel and flexible forming technology that has been used in the last few years to obtain a variety of customized sheet parts. One of the most valuable advantages of this process is its ability to suppress the localized necking of the sheet, allowing a stable plastic deformation up to the ductile fracture of the sheet. Traditionally the fracture in sheet metal forming is characterized by the conventional Fracture Forming Limit (FFL) curve, obtained with Nakazima or Marziniak tests. However, in many cases the SPIF processes exhibit fracture strains clearly above the conventional FFL, showing an unexpected gain of formability. It is well known that ductile fracture in metals is highly affected by the stress state in the material. Therefore, among others, this fact could contribute to explain the experimental differences observed in the FFL obtained by conventional and incremental operations. The present work develops a numerical model in ANSYS to study the mechanics of the fracture process during the incremental deformation operation. The simulations focus on the hole-flanging operation by SPIF in AA7075-O metal sheets of 1.6mm thickness, recently experimentally analysed by the authors. Different configurations of pre-cut hole diameters are simulated. The evolution of the strain paths and the hydrostatic stress in the SPIF process are analysed and discussed. These variables help to explain the apparent enhancement of formability observed in SPIF processes beyond the conventional FFL curve.

Behavioral activation: Is it the expectation or achievement, of mastery or pleasure that contributes to improvement in depression?

BackgroundBehavioral activation (BA) is receiving renewed interest as a stand-alone or as a component of cognitive-behavior therapy (CBT) for depression. However, few studies have examined which aspects of BA are most contributory to its efficacy. MethodsThis is a secondary analysis of a 9-week randomized controlled trial of smartphone CBT for patients with major depression. Depression severity was measured at baseline and at end of treatment by the Patient Health Questionnaire-9. All aspects of behavioral activation tasks that the participants had engaged in, including their expected mastery and pleasure and obtained mastery and pleasure, were recorded in the web server. We examined their contribution to improvement in depression as simple correlations and in stepwise multivariable linear regression. ResultsAmong the 78 patients who completed at least one behavioral experiment, all aspects of expected or achieved mastery or pleasure correlated with change in depression severity. Discrepancy between the expectation and achievement, representing unexpected gain in mastery or pleasure, was not correlated. In stepwise regression, expected mastery and pleasure, especially the maximum level of the latter, emerged as the strongest contributing factors. LimitationsThe study is observational and cannot deduce cause-effect relationships. ConclusionsIt may be the expected and continued sense of pleasure in planning activities that are most meaningful and rewarding to individuals, and not the simple level or amount of obtained pleasure, that contributes to the efficacy of BA.

Unexpected Weight Gain Following Long Term Increased Mvpa Is Linked To Elevated Respiratory Quotient

Unexpected Weight Gain Following Long Term Increased Mvpa Is Linked To Elevated Respiratory Quotient

Expectation modulates neural representations of valence throughout the human brain

The brain's sensitivity to unexpected gains or losses plays an important role in our ability to learn new behaviors (Rescorla and Wagner, 1972; Sutton and Barto, 1990). Recent work suggests that gains and losses are ubiquitously encoded throughout the human brain (Vickery et al., 2011), however, the extent to which reward expectation modulates these valence representations is not known. To address this question, we analyzed recordings from 4306 intracranially implanted electrodes in 39 neurosurgical patients as they performed a two-alternative probability learning task. Using high-frequency activity (HFA, 70–200Hz) as an indicator of local firing rates, we found that expectation modulated reward-related neural activity in widespread brain regions, including regions that receive sparse inputs from midbrain dopaminergic neurons. The strength of unexpected gain signals predicted subjects' abilities to encode stimulus–reward associations. Thus, neural signals that are functionally related to learning are widely distributed throughout the human brain.

Mechanisms linking connexin mutations to human diseases.

Ubiquitously expressed connexins are tetra-spanning transmembrane proteins that form intercellular gap junction channels or cell surface hemichannels. Connexins share similar topology but no sequence homology with mammalian pannexins and CALHM1 (calcium homeostasis modulator 1), which are also large-pore transmembrane channels. Of these three channel types, clinical evidence and gene sequence analysis to date have revealed that inherited human diseases are only associated with mutations in the connexin gene family. Connexin-linked diseases often present at birth or early in life and range from mild developmental abnormalities to severe organ failure such as hearing loss. Inherited connexin gene mutations can manifest as a disease by causing anomalies or defects in connexin oligomerization, folding, ability to pass quality control mechanisms or unexpected gain- or loss-of-function. This review provides examples of the way that various connexin gene mutations can cause disease via a wide range of molecular mechanisms. We also reflect on exciting strategies being explored in the connexin field and beyond with a view of translating their findings into potential connexin-disease therapeutics.

Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer

We recently demonstrated that plectin is a robust biomarker for pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies. In normal physiology, plectin is an intracellular scaffolding protein, but we have demonstrated localization on the extracellular surface of PDAC cells. In this study, we confirmed cell surface localization. Interestingly, we found that plectin cell surface localization was attributable to its presence in exosomes secreted from PDAC cells, which is dependent on the expression of integrin β4, a protein known to interact with cytosolic plectin. Moreover, plectin expression was necessary for efficient exosome production and was required to sustain enhanced tumor growth in immunodeficient and in immunocompetent mice. It is now clear that this PDAC biomarker plays a role in PDAC, and further understanding of plectin's contribution to PDAC could enable improved therapies.

Weight Gain While Switching from Polypharmacy to Ziprasidone: A Case Report

Second-generation antipsychotics (SGAs), valproate, and sulpiride are related to significant weight gain and risk of metabolic syndrome (MetS). Among SGAs, olanzapine and clozapine are associated with the highest metabolic risk while ziprasidone is among one of the SGAs with the lowest risk. Several reports suggest that weight loss is observed in switching other antipsychotics to ziprasidone. Here we describe a female patient with chronic paranoid schizophrenia who had an unexpected weight gain and developed MetS during a cross-switch from a polypharmacy of olanzapine, valproate and sulpiride to ziprasidone monotherapy.

Positive income shocks and accidental deaths among Cherokee Indians: a natural experiment.

Several studies in low-income populations report the somewhat counterintuitive finding that positive income gains adversely affect adult health. The literature posits that receipt of a large portion of annual income increases, in the short term, risk-taking behaviour and/or the consumption of health-damaging goods. This work implies the hypothesis that persons with an unexpected gain in income will exhibit an elevated risk of accidental death-the fifth leading cause of death in the USA. We test this hypothesis directly by capitalizing on a natural experiment in which Cherokee Indians in rural North Carolina received discrete lump sum payments from a new casino. We applied Poisson regression to the monthly count of accidental deaths among Cherokee Indians over 204 months spanning 1990-2006. We controlled for temporal patterns in accidental deaths (e.g. seasonality and trend) as well as changes in population size. As hypothesized, the risk of accidental death rises above expected levels during months of the large casino payments (relative risk = 2.62; 95% confidence interval = 1.54-4.47). Exploratory analyses of ethnographic interviews and behavioural surveys support that increased vehicular travel and consumption of health-damaging goods may account for the rise in accident proneness. Although long-term income gains may improve health in this population, our findings indicate that acute responses to large income gains, in the short term, increase risk-taking and accident proneness. We encourage further investigation of natural experiments to identify causal economic antecedents of population health.

Increased Neurotransmitter Release at the Neuromuscular Junction in a Mouse Model of Polyglutamine Disease

In Huntington's disease (HD), the expansion of polyglutamine (polyQ) repeats at the N terminus of the ubiquitous protein huntingtin (htt) leads to neurodegeneration in specific brain areas. Neurons degenerating in HD develop synaptic dysfunctions. However, it is unknown whether mutant htt impacts synaptic function in general. To investigate that, we have focused on the nerve terminals of motor neurons that typically do not degenerate in HD. Here, we have studied synaptic transmission at the neuromuscular junction of transgenic mice expressing a mutant form of htt (R6/1 mice). We have found that the size and frequency of miniature endplate potentials are similar in R6/1 and control mice. In contrast, the amplitude of evoked endplate potentials in R6/1 mice is increased compared to controls. Consistent with a presynaptic increase of release probability, synaptic depression under high-frequency stimulation is higher in R6/1 mice. In addition, no changes were detected in the size and dynamics of the recycling synaptic vesicle pool. Moreover, we have found increased amounts of the synaptic vesicle proteins synaptobrevin 1,2/VAMP 1,2 and cysteine string protein-α, and the SNARE protein SNAP-25, concomitant with normal levels of other synaptic vesicle markers. Our results reveal that the transgenic expression of a mutant form of htt leads to an unexpected gain of synaptic function. That phenotype is likely not secondary to neurodegeneration and might be due to a primary deregulation in synaptic protein levels. Our findings could be relevant to understand synaptic toxic effects of proteins with abnormal polyQ repeats.

Unexpected gain

A newly identified physical process in the interaction of strong laser fields with matter paves the way for broadband amplification of light in the extreme ultraviolet to soft-X-ray spectral region.

A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome

Mental retardation in Down syndrome (DS), the most frequent trisomy in humans, varies from moderate to severe. Several studies both in human and based on mouse models identified some regions of human chromosome 21 (Hsa21) as linked to cognitive deficits. However, other intervals such as the telomeric region of Hsa21 may contribute to the DS phenotype but their role has not yet been investigated in detail. Here we show that the trisomy of the 12 genes, found in the 0.59 Mb (Abcg1–U2af1) Hsa21 sub-telomeric region, in mice (Ts1Yah) produced defects in novel object recognition, open-field and Y-maze tests, similar to other DS models, but induces an improvement of the hippocampal-dependent spatial memory in the Morris water maze along with enhanced and longer lasting long-term potentiation in vivo in the hippocampus. Overall, we demonstrate the contribution of the Abcg1–U2af1 genetic region to cognitive defect in working and short-term recognition memory in DS models. Increase in copy number of the Abcg1–U2af1 interval leads to an unexpected gain of cognitive function in spatial learning. Expression analysis pinpoints several genes, such as Ndufv3, Wdr4, Pknox1 and Cbs, as candidates whose overexpression in the hippocampus might facilitate learning and memory in Ts1Yah mice. Our work unravels the complexity of combinatorial genetic code modulating different aspect of mental retardation in DS patients. It establishes definitely the contribution of the Abcg1–U2af1 orthologous region to the DS etiology and suggests new modulatory pathways for learning and memory.