Compensatory changes after spinal cord injury in a remyelination deficient mouse model.

The development of therapeutic strategies to reduce impairments following spinal cord injury (SCI) motivates an active area of research, because there are no effective therapies. One strategy is to address injury-induced demyelination of spared axons by promoting endogenous or exogenous remyelination. However, previously, we showed that new myelin was not necessary to regain hindlimb stepping following moderate thoracic spinal cord contusion in 3-month-old mice. The present analysis investigated two potential mechanisms by which animals can re-establish locomotion in the absence of remyelination: compensation through intact white matter and conduction through spared axons. We induced a severe contusion injury to reduce the spared white matter rim in the remyelination deficient model, with no differences in recovery between remyelination deficient animals and injured littermate controls. We investigated the nodal properties of the axons at the lesion and found that in the remyelination deficient model, axons express the Nav1.2 voltage-gated sodium channel, a sub-type not typically expressed at mature nodes of Ranvier. In a moderate contusion injury, conduction velocities through the lesions of remyelination deficient animals were similar to those in animals with the capacity to remyelinate after injury. Detailed gait analysis and kinematics reveal subtle differences between remyelination deficient animals and remyelination competent controls, but no worse deficits. It is possible that upregulation of Nav1.2 channels may contribute to establishing conduction through the lesion. This conduction could contribute to compensation and regained motor function in mouse models of SCI. Such compensatory mechanism may have implications for interpreting efficacy results for remyelinating interventions in mice and the development of therapies for improving recovery following SCI.

Reputational costs of receptiveness: When and why being receptive to opposing political views backfires.

A fast-growing body of research finds that receptiveness to opposing political views carries reputational benefits. A different body of research finds that opposing political views and the people who hold them are seen as repugnant. How could it be that people receptive to opposing political ideas are viewed positively when the political opponents they are receptive to are seen negatively? In seven main (N = 5,286) and nine supplemental studies (N = 3,983 participants in online studies; N = 124,493 observations in field data), we reconcile this tension by arguing that the identity of the person one is receptive to determines whether receptiveness carries reputational benefits or costs. When the information source belongs to the opposing party, receptiveness to opposing political views often carries reputational costs. We find these reputational costs across both strong and weak signals of receptiveness, eight different political and social issues, and multiple types of prototypical out-party sources. We argue that these costs arise because members of the opposing party are frequently stereotyped as immoral, and thus receptiveness to their ideas is seen negatively. As a boundary condition, we find that the costs of receptiveness are pronounced for sources who are prototypical of the out-party and attenuate (or even reverse) for sources who are nonprototypical. These findings resolve a seeming contradiction between two distinct literatures in psychology, contribute to a rapidly expanding literature on the interpersonal consequences of receptiveness, and lay the groundwork for understanding novel barriers to, and ultimately solutions for, the lack of cross-party openness and political polarization. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Passive sea ice thickness inference using cryophones.

Mechanical properties of Arctic sea ice can be inferred by observations of in-ice propagation of compressional, shear, and flexural waves. During the 1980s, impulsive signals were generated by a lead ball or sledgehammer dropped onto the sea ice, and the inference required observation of wave speeds. During ICEX20 and ARCEX23, passive cryophone observations were made of naturally occurring compressional wave resonances. Average first-year ice thicknesses during ICEX20 and ARCEX23 were inferred to be 1.3 and 1.6 m, respectively; these are consistent with independent observations and indicate the potential for remote, autonomous monitoring of sea ice thickness.

Tailoring recommendation algorithms to ideal preferences makes users better off.

People often struggle to do what they ideally want because of a conflict between their actual and ideal preferences. ​​​By focusing on maximizing engagement, recommendation algorithms appear to be exacerbating this struggle. However, this need not be the case. Here we show that tailoring recommendation algorithms to ideal (vs. actual) preferences would provide meaningful benefits to both users and companies. To examine this, we built algorithmic recommendation systems that generated real-time, personalized recommendations tailored to either a person's actual or ideal preferences. Then, in a high-powered, pre-registered experiment (n = 6488), we measured the effects of these recommendation algorithms. We found that targeting ideal rather than actual preferences resulted in somewhat fewer clicks, but it also increased the extent to which people felt better off and that their time was well spent. Moreover, of note to companies, targeting ideal preferences increased users' willingness to pay for the service, the extent to which they felt the company had their best interest at heart, and their likelihood of using the service again. Our results suggest that users and companies would be better off if recommendation algorithms learned what each person was striving for and nudged individuals toward their own unique ideals.

Patient-reported treatment toxicity and adverse events in Black and White women receiving chemotherapy for early breast cancer.

PURPOSE: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. METHODS: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. CONCLUSION: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.

[Prevalence of visual impairment in school-age children: Data analysis from PlanVue® pilot project]. / Dépistage des troubles visuels à l'âge scolaire : les données du projet pilote PlanVue®.

PURPOSE: To assess the prevalence of visual disturbances among school-aged children in prioritized education zones in France. METHODS: The PlanVue® pilot project was designed to detect and manage visual disturbances in school-aged children in the prioritized education areas of the city of Nanterre, France. During this pilot study, a cohort of 515 children aged 4 to 13 years underwent a school vision screening between January and March 2019, consisting of an overall evaluation of the child's visual behavior, measurement of uncorrected visual acuity in each eye, objective refraction with a photoscreener and strabismus screening. If the examination was abnormal as determined by impaired vision or an algorithm based on the abnormalities found, the children were referred to an ophthalmologist. RESULTS: Decreased visual acuity was found in 20% of school-aged children. Out of the 515 children screened, 22% were referred to an ophthalmologist. Among these children, 13% were diagnosed with amblyopia, 73% with spherical ametropia, 57% with astigmatism and 2% with strabismus. Of the entire population screened, 12% of the children needed optical correction but had not received glasses. CONCLUSION: This study confirms the high prevalence of uncorrected refractive errors among school-age children. A screening program carried out in a school environment by paramedical professionals might make it possible to considerably reduce the rate of uncorrected visual disorders and their consequences.

Objects and self-identity.

This article reviews how objects can serve as indicators of one's identity and signals of important life events. Objects carry both personal and social meaning, and ownership or usage increases the linkage between the object and the self. Owned objects are valued more due to their linkage with the (positively viewed) self. Similarly, self-views can assimilate to the associations of the owned or used object. We rely on the insights of consistency theories (e.g. Balance Theory) to provide a unifying umbrella for the literature, and we review how the acquisition and abandonment of objects can shape self-views, affect task performance, and serve as inward and outward signals of group membership.

Hendra in the Hunter Valley.

In June 2019 the first equine case of Hendra virus in the Hunter Valley, New South Wales, Australia was detected. An urgent human and animal health response took place, involving biosecurity measures, contact tracing, promotion of equine vaccinations and investigation of flying fox activity in the area. No human or additional animal cases occurred. Equine vaccination uptake increased by over 30-fold in the surrounding region in the three months following the case. Black flying fox and grey-headed flying fox species were detected in the Valley. The incident prompted review of Hendra virus resources at local and national levels. This event near the "horse capital of Australia", is the southernmost known equine Hendra case. Management of the event was facilitated by interagency collaboration involving human and animal health experts. Ongoing One Health partnerships are essential for successful responses to future zoonotic events.

Evaporation-induced Rayleigh-Taylor instabilities in polymer solutions.

Understanding the mechanics of detrimental convective instabilities in drying polymer solutions is crucial in many applications such as the production of film coatings. It is well known that solvent evaporation in polymer solutions can lead to Rayleigh-Bénard or Marangoni-type instabilities. Here, we reveal another mechanism, namely that evaporation can cause the interface to display Rayleigh-Taylor instabilities due to the build-up of a dense layer at the air-liquid interface. We study experimentally the onset time (tp) of the instability as a function of the macroscopic properties of aqueous polymer solutions, which we tune by varying the polymer concentration (c0), molecular weight and polymer type. In dilute solutions, tp shows two limiting behaviours depending on the polymer diffusivity. For high diffusivity polymers (low molecular weight), the pluming time scales as [Formula: see text]. This result agrees with previous studies on gravitational instabilities in miscible systems where diffusion stabilizes the system. On the other hand, in low diffusivity polymers the pluming time scales as [Formula: see text]. The stabilizing effect of an effective interfacial tension, similar to those in immiscible systems, explains this strong concentration dependence. Above a critical concentration, [Formula: see text], viscosity delays the growth of the instability, allowing time for diffusion to act as the dominant stabilizing mechanism. This results in tp scaling as (ν/c0)2/3. This article is part of the theme issue 'Stokes at 200 (Part 1)'.

Suppression of circadian secretion of glucagon-like peptide-1 by the saturated fatty acid, palmitate.

AIM: Glucagon-like peptide-1 is an incretin hormone secreted by the intestinal L-cell with a circadian rhythm that parallels expression of the core clock gene, Bmal1. Although feeding rats a high-fat/high-sucrose Western diet impairs rhythmic glucagon-like peptide-1 release, the mechanisms underlying this effect remain unclear. Therefore, the aim of this study was to determine the pathway(s) by which the saturated fat, palmitate, a major component of the Western diet, impairs circadian glucagon-like peptide-1 secretion. METHODS: Murine mGLUTag L-cells were synchronized, and the effects of palmitate pre-treatment on gene expression and glucagon-like peptide-1 secretion were determined, in addition to metabolite quantification, mitochondrial function analysis and enzyme inhibition and activation assays. Glucagon-like peptide-1 secretion was also analysed in ileal crypt cultures from control and Bmal1 knockout mice. RESULTS: Pre-treatment with palmitate dampened Bmal1 mRNA and protein expression and glucagon-like peptide-1 secretion at 8 but not 20 hours after cell synchronization (P < .05-.001). Glucagon-like peptide-1 release was also impaired in Bmal1 knockout cultures as compared to wild-type controls (P < .001). Palmitate pre-treatment reduced expression of the Bmal1 downstream target, nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the synthesis of NAD+ . This was paralleled by dampening of total NAD+ levels, as well as impaired mitochondrial function and ATP production (P < .05-.001). Whereas direct inhibition of nicotinamide phosphoribosyltransferase also decreased glucagon-like peptide-1 release, activation of this enzyme restored glucagon-like peptide-1 secretion in the presence of palmitate. CONCLUSION: Palmitate impairs L-cell clock function at the peak of Bmal1 gene expression, thereby impairing mitochondrial function and ultimately rhythmic glucagon-like peptide-1 secretion.

A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties.

Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells. However, we observed that the dormant cells were localized primarily within the 3D tissue, while the proliferative cells were in contact with the polystyrene scaffold. As matrix stiffness is known to drive inflammatory and malignant behaviors, we explored the occurrence of spontaneous tumor dormancy and inflammatory phenotype. The microphysiological system was retrofitted with PEGDa-SynKRGD hydrogel scaffolding, which is softer and differs in the interface with the tissue. The microphysiological system incorporated donor-matched primary human hepatocytes and non-parenchymal cells (NPCs), with MDA-MB-231 breast cancer cells. Hepatic tissue in hydrogel scaffolds secreted lower levels of pro-inflammatory analytes, and was more responsive to inflammatory stimuli. The proportion of tumor cells entering dormancy was markedly increased in the hydrogel-supported tissue compared to polystyrene. Interestingly, an unexpected differential response of dormant cells to varying chemotherapeutic doses was identified, which if reflective of patient pathophysiology, has important implications for patient dosing regimens. These findings highlight the metastatic microphysiological system fitted with hydrogel scaffolds as a critical tool in the assessment and development of therapeutic strategies to target dormant metastatic breast cancer.

Wanting to Be Different Predicts Nonmotivated Change: Actual-Desired Self-Discrepancies and Susceptibility to Subtle Change Inductions.

Actual-desired discrepancies in people's self-concepts represent structural incongruities in their self-representations that can lead people to experience subjective conflict. Theory and research suggest that structural incongruities predict susceptibility to subtle influences like priming and conditioning. Although typically examined for their motivational properties, we hypothesized that because self-discrepancies represent structural incongruities in people's self-concepts, they should also predict susceptibility to subtle influences on people's active self-views. Across three studies, we found that subtle change inductions (self-evaluative conditioning and priming) exerted greater impact on active self-perceptions and behavior as actual-desired self-discrepancies increased in magnitude. Exploratory analyses suggested that these changes occurred regardless of the compatibility of the change induction with individuals' desired self-views.

Belief in the immutability of attitudes both increases and decreases advocacy.

People with an entity theory of attitudes (i.e., the belief that attitudes are relatively unchanging) are more certain of their attitudes than are people with an incremental theory (i.e., the belief that attitudes are relatively malleable), and people with greater attitude certainty are generally more willing to try to persuade others. Combined, these findings suggest that an entity theory should foster greater advocacy. Yet, people with entity theories may be less willing to advocate because they also perceive others' attitudes as unchanging. Across 5 studies, we show that both of these countervailing effects occur simultaneously and cancel each other out. However, by manipulating how advocacy is framed (as standing up for one's views or exchanging one's views with others), whom people focus on (themselves or others), or which implicit theory applies to oneself versus others, each implicit theory can either increase or decrease willingness to advocate. (PsycINFO Database Record

Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection.

Point of care molecular diagnostics benefits from a portable battery-operated device capable of performing a fast turnaround using reliable inexpensive cartridges. We describe a prototype device for performing a molecular diagnostics test for clinical and biodefense samples in 16 minutes using a prototype capable of an 8 minute PCR reaction, followed by hybridization and detection on an electrochemical microarray based on the i-STAT® system. We used human buccal swabs for hemochromatosis testing including in-device DNA extraction. Additional clinical and biodefense samples included influenza A and bacterial select agents Bacillus anthracis, Yersinia pestis and Francisella tularensis.

The good and bad of ambivalence: Desiring ambivalence under outcome uncertainty.

Decades of past research point to the downside of evaluative inconsistency (i.e., ambivalence), suggesting that it is an unpleasant state that can result in negative affect. Consequently, people are often motivated to resolve their ambivalence in various ways. We propose that people sometimes desire to be ambivalent as a means of strategic self-protection. Across employment, educational and consumer choice settings, we demonstrate that when people are uncertain they can obtain a desired target, they will cultivate ambivalence in order to protect their feelings in the event that they fail to get what they want. Specifically, we show that people consciously desire to cultivate ambivalence as a way to emotionally hedge and that they seek out and process information in ways to deliberately cultivate ambivalence. We find that people are most likely to generate ambivalence when they are most uncertain that they can obtain their desired target. Depending on the outcome, this cultivated ambivalence can either be useful (when the desired target is not obtained) or backfire (when the desired target is obtained).

Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors.

The development of targeted therapies based on specific genomic alterations has altered the treatment and management of lung and colorectal cancers. Chromosomal microarray (CMA) has allowed identification of copy number variations (CNVs) in lung and colorectal cancers in great detail, and next-generation sequencing (NGS) is used extensively to analyze the genome of cancers for molecular subtyping and use of molecularly guided therapies. The main objective of this study was to evaluate the utility of combining CMA and NGS for a comprehensive genomic assessment of lung and colorectal adenocarcinomas, especially for detecting drug targets. We compared the results from NGS and CMA data from 60 lung and 51 colorectal tumors. From CMA analysis, 33% were amplified, 89% showed gains, 75% showed losses and 41% demonstrated loss of heterozygosity; pathogenic variants were identified in 81% of colon and 67% lung specimens through NGS. KRAS mutations commonly occurred with loss in TP53 and there was significant loss of BRCA1 and NF1 among male patients with lung cancer. For clinically actionable targets, 23% had targetable CNVs when no pathogenic variants were detected by NGS. The data thus indicate that combining the two approaches provides significant benefit in a routine clinical setting not available by NGS alone.

On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings.

Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring.

Reduced voltage losses yield 10% efficient fullerene free organic solar cells with >1 V open circuit voltages.

Optimization of the energy levels at the donor-acceptor interface of organic solar cells has driven their efficiencies to above 10%. However, further improvements towards efficiencies comparable with inorganic solar cells remain challenging because of high recombination losses, which empirically limit the open-circuit voltage (Voc) to typically less than 1 V. Here we show that this empirical limit can be overcome using non-fullerene acceptors blended with the low band gap polymer PffBT4T-2DT leading to efficiencies approaching 10% (9.95%). We achieve Voc up to 1.12 V, which corresponds to a loss of only Eg/q - Voc = 0.5 ± 0.01 V between the optical bandgap Eg of the polymer and Voc. This high Voc is shown to be associated with the achievement of remarkably low non-geminate and non-radiative recombination losses in these devices. Suppression of non-radiative recombination implies high external electroluminescence quantum efficiencies which are orders of magnitude higher than those of equivalent devices employing fullerene acceptors. Using the balance between reduced recombination losses and good photocurrent generation efficiencies achieved experimentally as a baseline for simulations of the efficiency potential of organic solar cells, we estimate that efficiencies of up to 20% are achievable if band gaps and fill factors are further optimized.

A method comparison of a food frequency questionnaire to measure folate, choline, betaine, vitamin C and carotenoids with 24-h dietary recalls in women of reproductive age.

BACKGROUND/OBJECTIVES: The objective of this study was to conduct a method comparison of a modified food frequency questionnaire (FFQ), designed to estimate usual dietary intake of selected micronutrients and antioxidants including folate, choline, betaine, vitamin C and carotenoids (α-carotene, ß-carotene, lutein, lycopene and ß-cryptoxanthin) with 24-h dietary recalls (24-HR) in women of reproductive age. SUBJECTS/METHODS: Sixty-four British women of reproductive age (18-40 years) were recruited in Oxford, UK and provided complete dietary data for analysis. METHODS: We compared micronutrient estimates from the FFQ against estimates derived from three multiple-pass, 24-HR interviews, by evaluating Pearson's correlation coefficients and Bland-Altman plots. RESULTS: Median intakes of most nutrients were higher when measured by FFQ compared with 24-HR. Strong correlation coefficients were observed for folate (r=0.80) and choline (r=0.68), whereas moderate correlation coefficients were observed for vitamin C (0.50) and lycopene (0.43). Weak correlation coefficients were observed for betaine (0.39) and other carotenoids (r=0.26-0.38). Bland-Altman plots indicated that there was a large amount of variability in the FFQ estimates of nutrient intakes compared to those using 24-HR, particularly for carotenoids. CONCLUSIONS: The findings indicate that this FFQ estimated higher mean intakes for most nutrients. Pearson's correlation coefficients were comparable with previous research; however, the Bland-Altman plots suggest a high variability in mean nutrient estimates between the FFQ and 24-h. We recommend further investigation of the validity of this FFQ before use.