Search

Hindbrain growth hormone secretagogue receptor (GHSR) agonism increases food intake, yet the underlying neural mechanisms remain unclear. The functional effects of hindbrain GHSR antagonism by its endogenous antagonist liver-expressed antimicrobial peptide 2 (LEAP2) are also yet unexplored. To test the hypothesis that hindbrain GHSR agonism attenuates the food intake inhibitory effect of gastrointestinal (GI) satiation signals, ghrelin (at a feeding subthreshold dose) was administered to the fourth ventricle (4V) or directly to the nucleus tractus solitarius (NTS) before systemic delivery of the GI satiation signal cholecystokinin (CCK). Also examined, was whether hindbrain GHSR agonism attenuated CCK-induced NTS neural activation (c-Fos immunofluorescence). To investigate an alternate hypothesis that hindbrain GHSR agonism enhances feeding motivation and food seeking, intake stimulatory ghrelin doses were administered to the 4V and fixed ratio 5 (FR-5), progressive ratio (PR), and operant reinstatement paradigms for palatable food responding were evaluated. Also assessed were 4V LEAP2 delivery on food intake and body weight (BW) and on ghrelin-stimulated feeding. Both 4V and NTS ghrelin blocked the intake inhibitory effect of CCK and 4V ghrelin blocked CCK-induced NTS neural activation. Although 4V ghrelin increased low-demand FR-5 responding, it did not increase high-demand PR or reinstatement of operant responding. Fourth ventricle LEAP2 reduced chow intake and BW and blocked hindbrain ghrelin-stimulated feeding. Data support a role for hindbrain GHSR in bidirectional control of food intake through mechanisms that include interacting with the NTS neural processing of GI satiation signals but not food motivation and food seeking.

The Interactions website (interactions.acm.org) hosts a stable of bloggers who share insights and observations on HCI, often challenging current practices. Each issue we'll publish selected posts from some of the leading and emerging voices in the field.

Cs salts of tungstophosphoric acid supported mZS with varying amounts of Cs ions content have been prepared by a two-step impregnation technique, and found to be effective for the removal of hazardous dyes such as MB from an aqueous solution.

Background Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are heterogeneous in clinical course, biology, and outcomes. The NETPET score predicts survival by scoring uptake on dual [68Ga]DOTATATE and [18F]FDG PET/CT scans. We aimed to validate previous single-centre findings in a multicentre, international study. Methods Dual scans were assigned a NETPET score of P1 (DOTATATE positive/FDG negative), P2–4 (DOTATATE positive/FDG positive), or P5 (DOTATATE negative/FDG positive). NETPET score, histological grade, age at diagnosis, and presence/absence of extrahepatic disease were compared to overall survival/time to progression on univariate and multivariate analysis. Results 319 metastatic/unresectable GEPNEN patients were included. The NETPET score was significantly associated with overall survival and time to progression on univariate and multivariate analysis (all p p p p Conclusion This study validates the NETPET score as a prognostic biomarker in metastatic GEPNENs, capturing the complexity of dual PET imaging.

People living with dementia as well as dementia caregivers are finding new ways to provide and receive support online. The emerging use of social media platforms-such as TikTok, Clubhouse, and Facebook-by people with dementia and dementia caregivers enables new forms of sharing about stigmatized, poorly understood, and often under-discussed experiences. Building on prior work focused on formal support groups, we report findings from an interview study of how people living with dementia and dementia caregivers provide and receive social support through emerging online spaces and communities. Our analysis reveals that both groups cultivate new online spaces for sharing about the experience of dementia while also navigating tensions surrounding public disclosure of lived experiences, advocacy, education, and the ability to protect and keep private elements of life experiences. We discuss how these groups cultivate online spaces across platforms and contribute to ongoing ethical debates about consent in online communities. We conclude with questions that guide future work on emerging online spaces for supporting people living with dementia and caregivers of people living with dementia.

The center of the Milky Way contains stellar populations spanning a range in age and metallicity, with a recent star formation burst producing young and massive stars. Chemical abundances in the most luminous stellar member of the Nuclear Star Cluster (NSC), IRS 7, are presented for $^{19}$F, $^{12}$C, $^{13}$C, $^{14}$N, $^{16}$O, $^{17}$O, and Fe from an LTE analysis based on spherical modeling and radiative transfer with a 25M$_{\odot}$ model atmosphere, whose chemistry was tailored to the derived photospheric abundances. We find IRS 7 to be depleted heavily in both $^{12}$C (~-0.8 dex) and $^{16}$O (~-0.4 dex), while exhibiting an extremely enhanced $^{14}$N abundance (~+1.1 dex), which are isotopic signatures of the deep mixing of CNO-cycled material to the stellar surface. The $^{19}$F abundance is also heavily depleted by ~1 dex relative to the baseline fluorine of the Nuclear Star Cluster, providing evidence that fluorine along with carbon constrain the nature of the deep mixing in this very luminous supergiant. The abundances of the minor isotopes $^{13}$C and $^{17}$O are also derived, with ratios of $^{12}$C/$^{13}$C~5.3 and $^{16}$O/$^{17}$O~525. The derived abundances for IRS 7, in conjunction with previous abundance results for massive stars in the NSC, are compared with rotating and non-rotating models of massive stars and it is found that the IRS 7 abundances overall follow the behavior predicted by stellar models. The depleted fluorine abundance in IRS 7 illustrates, for the first time, the potential of using the $^{19}$F abundance as a mixing probe in luminous red giants., Comment: 11 pages, 6 figures, 2 tables

Nuclear clearance and cytoplasmic mislocalization of the essential RNA binding protein, TDP-43, is a pathologic hallmark of amyotrophic lateral sclerosis, frontotemporal dementia, and related neurodegenerative disorders collectively termed “TDP-43 proteinopathies.” TDP-43 mislocalization causes neurodegeneration through both loss and gain of function mechanisms. Loss of TDP-43 nuclear RNA processing function destabilizes the transcriptome by multiple mechanisms including disruption of pre-mRNA splicing, the failure of repression of cryptic exons, and retrotransposon activation. The accumulation of cytoplasmic TDP-43, which is prone to aberrant liquid–liquid phase separation and aggregation, traps TDP-43 in the cytoplasm and disrupts a host of downstream processes including the trafficking of RNA granules, local translation within axons, and mitochondrial function. In this review, we will discuss the TDP-43 therapy development pipeline, beginning with therapies in current and upcoming clinical trials, which are primarily focused on accelerating the clearance of TDP-43 aggregates. Then, we will look ahead to emerging strategies from preclinical studies, first from high-throughput genetic and pharmacologic screens, and finally from mechanistic studies focused on the upstream cause(s) of TDP-43 disruption in ALS/FTD. These include modulation of stress granule dynamics, TDP-43 nucleocytoplasmic shuttling, RNA metabolism, and correction of aberrant splicing events. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01260-5.

Models of visual search in scenes include image salience as a source of attentional guidance. However, because scene meaning is correlated with image salience, it could be that the salience predictor in these models is driven by meaning. To test this proposal, we generated meaning maps that represented the spatial distribution of semantic informativeness in scenes, and salience maps which represented the spatial distribution of conspicuous image features and tested their influence on fixation densities from two object search tasks in real-world scenes. The results showed that meaning accounted for significantly greater variance in fixation densities than image salience, both overall and in early attention across both studies. Here, meaning explained 58% and 63% of the theoretical ceiling of variance in attention across both studies, respectively. Furthermore, both studies demonstrated that fast initial saccades were not more likely to be directed to higher salience regions than slower initial saccades, and initial saccades of all latencies were directed to regions containing higher meaning than salience. Together, these results demonstrated that even though meaning was task-neutral, the visual system still selected meaningful over salient scene regions for attention during search.

Humans rapidly process and understand real-world scenes with ease. Our stored semantic knowledge gained from experience is thought to be central to this ability by organizing perceptual information into meaningful units to efficiently guide our attention in scenes. However, the role stored semantic representations play in scene guidance remains difficult to study and poorly understood. Here, we apply a state-of-the-art multimodal transformer trained on billions of image-text pairs to help advance our understanding of the role semantic representations play in scene understanding. We demonstrate across multiple studies that this transformer-based approach can be used to automatically estimate local scene meaning in indoor and outdoor scenes, predict where people look in these scenes, detect changes in local semantic content, and provide a human-interpretable account of why one scene region is more meaningful than another. Taken together, these findings highlight how multimodal transformers can advance our understanding of the role scene semantics play in scene understanding by serving as a representational framework that bridges vision and language.

Cytoplasmic inclusions and loss of nuclear TDP-43 are key pathological features found in several neurodegenerative disorders, suggesting both gain- and loss-of-function mechanisms of disease. To study gain-of-function, TDP-43 overexpression has been used to generatein vitroandin vivomodel systems. Our study shows that excessive levels of nuclear TDP-43 protein lead to constitutive exon skipping that is largely species-specific. Furthermore, while aberrant exon skipping is detected in some human brains, it is not correlated with disease, unlike the incorporation of cryptic exons that occurs after loss of TDP-43. Our findings emphasize the need for caution in interpreting TDP-43 overexpression data, and stress the importance of controlling for exon skipping when generating models of TDP-43 proteinopathy. Understanding the subtle aspects of TDP-43 toxicity within different subcellular locations is essential for the development of therapies targeting neurodegenerative disease.

Heart rate is an extremely important physiological parameter to measure in critically unwell infants, as it is the main physiological marker that changes in response to a change in infant condition. Heart rate is routinely measured peripherally on a limb with a pulse oximeter. However, when infants are critically unwell, the blood supply to these peripheries is reduced in preference for central perfusion of vital organs such as the brain and heart. Measurement of heart rate with a reflection mode photoplethysmogram (PPG) sensor on the forehead could help minimise this problem and make it easier for other important medical equipment, such as cannulas, to be placed on the limbs. This study compares heart rates measured with a forehead-based PPG sensor against a wrist-based PPG sensor in 19 critically unwell infants in neonatal intensive care collecting 198 h of data. The two heart rates were compared using positive percentage agreement, Spearman’s correlation coefficient and Bland-Altman analysis. The forehead PPG sensor showed good agreement with the wrist-based PPG sensor with limits of agreement of 8.44 bpm, bias of −0.22 bpm; positive percentage agreement of 98.87%; and Spearman’s correlation coefficient of 0.9816. The analysis demonstrates that the forehead is a reliable alternative location for measuring vital signs using the PPG.

The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes in male rats. Specifically, results reveal that MCH neuron Ca2+ activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating, and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes., Nature Communications, 14 (1), ISSN:2041-1723

As we act on the world around us, our eyes seek out objects we plan to interact with. A growing body of evidence suggests that overt visual attention selects objects in the environment that could be interacted with, even when the task precludes physical interaction. In previous work, objects that afford grasping interactions influenced attention when static scenes depicted reachable spaces, and attention was otherwise better explained by general informativeness. Because grasping is but one of many object interactions, previous work may have downplayed the influence of object affordances on attention. The current study investigated the relationship between overt visual attention and object affordances versus broadly construed semantic information in scenes as speakers describe or memorize scenes. In addition to meaning and grasp maps—which capture informativeness and grasping object affordances in scenes, respectively—we introduce interact maps, which capture affordances more broadly. In a mixed-effects analysis of 5 eyetracking experiments, we found that meaning predicted fixated locations in a general description task and during scene memorization. Grasp maps marginally predicted fixated locations during action description for scenes that depicted reachable spaces only. Interact maps predicted fixated regions in description experiments alone. Our findings suggest observers allocate attention to scene regions that could be readily interacted with when talking about the scene, while general informativeness preferentially guides attention when the task does not encourage careful consideration of objects in the scene. The current study suggests that the influence of object affordances on visual attention in scenes is mediated by task demands.

The HPTN 071(PopART) study was a community-randomised trial in Zambia and South Africa, examining the impact of combination-prevention including universal testing and treatment (UTT), on HIV-incidence. This sub-study evaluated factors associated with IPV (physical and/or sexual) to identify differences by HIV status. During 2015-16, a random subset of adults who participated in the first year of the PopART intervention were recruited and standardised questionnaires were administered. Logistic regression was performed to estimate odds ratios of factors associated with IPV. Among700 women studied (300 HIV-negative;400 HIV-positive), ~ 20% reported experiencing physical and/or sexual violence in the last 12-months. Sexual violence was similar by HIV status, but physical violence and reporting both physical/sexual violence was more common among HIV-positive women. Spending nights away from the community in the last 12-months was associated with higher odds of IPV among both HIV-negative (aOR 3.17, 95% CI 1.02-9.81) and HIV-positive women (aOR 1.79, 95% CI 0.99-3.24). Among HIV-positive women, financial autonomy was associated with reduced IPV (aOR:0.41,95%CI:0.23-0.75) while pregnancy in the last 12-months (aOR 2.25, 95% CI 1.07-4.74), risk of alcohol dependence (aOR 2.75, 95% CI 1.51-5.00) and risk of mental distress (aOR 2.62, 95% CI 1.33-5.16) were associated with increased IPV. Among HIV-negative women reporting sex in the last 12-months, transactional sex (aOR 3.97, 95% CI 1.02-15.37) and not knowing partner's HIV status (aOR 3.01, 95% CI 1.24-7.29) were associated with IPV. IPV was commonly reported in the study population and factors associated with IPV differed by HIV status. The association of mobility with IPV warrants further research. The high prevalence of harmful alcohol use and mental distress, and their association with IPV among HIV-positive women require urgent attention.El estudio HPTN 071 (PopART) fue un ensayo aleatorio-comunitario realizado en Zambia y Sudáfrica, que examinó el impacto de la prevención combinada, incluyendo las pruebas y tratamiento universal (UTT), en la incidencia del VIH. Este subestudio evaluó los factores asociados con la IPV (físicos y / o sexuales) para identificar diferencias en el estado del VIH. Durante 2015-16, un subconjunto aleatorio de adultos fueron reclutados para participar en el primer año de intervención de PopART, donde se administraron cuestionarios estandarizados. Se realizó una regresión logística para estimar las ratios de probabilidad de los factores asociados con la VPI. Entre las700 mujeres estudiadas (300 VIH negativas; 400 VIH positivas), ~ 20% informó haber experimentado violencia física y / o sexual en los últimos 12 meses. La violencia sexual fue similar en cuanto al estado del VIH. La denuncia de violencia física y sexual fue más común entre las mujeres VIH positivas. Pasar noches fuera de la comunidad en los últimos 12 meses, se asoció con mayores probabilidades de VPI entre las mujeres VIH negativas (ORa 3,17, 95% IC 1,02–9,81) y las mujeres VIH positivas (ORa 1,79, 95% IC 0,99–3,24). Entre las mujeres VIH positivas, la autonomía financiera se asoció con una reducción de la VPI (ORa 0,41; IC del 95% 0,23-0,75) mientras que en el embarazo en los últimos 12 meses (ORa 2,25; IC del 95% 1,07–4,74), riesgo a la dependencia del alcohol (ORa 2,75% IC 1,51–5,00) y el riesgo de angustia mental (ORa 2,62% IC del 95% 1,33–5,16) se asociaron con un aumento de la VPI. Entre las mujeres VIH negativas que informaron haber tenido relaciones sexuales en los últimos 12 meses, el sexo transaccional (ORa 3.97, 95% CI 1.02–15.37) y el desconocimiento del estado de VIH de la pareja (ORa 3.01, 95% CI 1.24–7.29) se asociaron con IPV. La IPV fue notificada mayoritariamente en la población de estudio y los factores asociados con la IPV diferían según el estado del VIH. La asociación de la movilidad con la IPV justifica una mayor investigación. La alta prevalencia de l consumo nocivo de alcohol y la angustia mental, y su asociación con la VPI entre las mujeres seropositivas, requieren atención urgente.

Gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) are widely heterogeneous in their biological behavior, and predicting prognosis and optimal treatment strategies can be challenging. 68Ga-DOTATATE PET/CT is a sensitive imaging modality for well-differentiated NEN and indicates a favorable prognosis, whereas 18F-FDG PET/CT avidity indicates disease that is potentially more aggressive. There has been emerging interest in the combined interpretation of 68Ga-DOTATATE and 18F-FDG PET and its prognostic significance. We aimed to assess the prognostic utility of a classification system that incorporates the complex findings of 68Ga-DOTATATE and 18F-FDG PET interpreted side-by-side in patients with metastatic GEP NEN.We defined 3 68Ga-DOTATATE/18F-FDG "dual-tracer PET" groups: D1 (68Ga-DOTATATE positive/18F-FDG negative), D2 (68Ga-DOTATATE positive/18F-FDG positive), and D3 (68Ga-DOTATATE negative/18F-FDG positive). We retrospectively assessed the association between the dual-tracer PET classification and progression-free and overall survival (OS) using Kaplan-Meier analysis. Univariate and multivariate analyses were performed using the Cox proportional hazards model.Eighty-seven patients with metastatic GEP NEN and contemporaneous 68Ga-DOTATATE and 18F-FDG PET were included. The dual-tracer PET classification was an independent predictor of OS (multivariate P = 0.016) and also predicted progression-free survival (univariate P = 0.030). Other independent predictors of OS included chromogranin A and World Health Organization (WHO) grade. WHO grade was not associated with OS from the time of dual-tracer PET but was an independent predictor of OS from the date of histological diagnosis (multivariate P = 0.003).Our study demonstrates that a classification system combining the complex findings of 68Ga-DOTATATE and 18F-FDG PET is correlated with prognosis. Further research is needed to prospectively validate these findings and to explore whether dual-tracer PET scores may also be able to predict response to treatment.

Therapeutic and bioengineering applications of cells, such as cell printing and cell delivery, are directly limited by cell damage and death due to harsh mechanical conditions. Improved cellular robustness thus motivates investigations into cell encapsulation that provides essential protection. Here we target the cell-surface glycocalyx and crosslink two layers of DNA origami nanorods on the cellular plasma membrane to form a nanoscale protective shell. This modular and programmable approach enables fine control over the layering and composition of membrane-deposited nanorods. We show that the DNA origami nanoshell modulates the biophysical properties of cell membranes by enhancing membrane stiffness and lowering lipid fluidity. Moreover, the nanoshell serves as armor, protecting cells, limiting swelling and ultimately improving their viability against mechanical stress from osmotic imbalance and centrifugal forces. Our results demonstrate the potential of the nanoshell, not only as a cellular protection strategy, but also as a platform for manipulating and studying plasma membrane mechanics.

Background More than half of cancers could be prevented by employing evidence-based interventions (EBIs), including prevention interventions targeting nutrition, physical activity, and tobacco. Federally qualified health centers (FQHCs) are the primary source of patient care for over 30 million Americans – making them an optimal setting for ensuring evidence-based prevention that advances health equity. The aims of this study are to: 1) determine the degree to which primary cancer prevention EBIs are being implemented within Massachusetts FQHCs and 2) describe how these EBIs are implemented internally and via community partnerships. Methods We used an explanatory sequential mixed methods design to assess the implementation of cancer prevention EBIs. First, we used quantitative surveys of FQHC staff to determine the frequency of EBI implementation. We followed up with qualitative one-on-one interviews among a sample of staff to understand how the EBIs selected on the survey were implemented. Exploration of contextual influences on implementation and use of partnerships was guided by the Consolidated Framework for Implementation Research (CFIR). Quantitative data were summarized descriptively, and qualitative analyses used reflexive, thematic approaches, beginning deductively with codes from CFIR, then inductively coding additional categories. Results All FQHCs indicated they offered clinic-based tobacco interventions, such as clinician-delivered screening practices and prescription of tobacco cessation medications. Quitline interventions and some diet/physical activity EBIs were available at all FQHCs, but staff perceptions of penetration were low. Only 38% of FQHCs offered group tobacco cessation counseling and 63% referred patients to mobile phone-based cessation interventions. We found multilevel factors influenced implementation across intervention types – including the complexity of intervention trainings, available time and staffing, motivation of clinicians, funding, and external policies and incentives. While partnerships were described as valuable, only one FQHC reported using clinical-community linkages for primary cancer prevention EBIs. Conclusions Adoption of primary prevention EBIs in Massachusetts FQHCs is relatively high, but stable staffing and funding are required to successfully reach all eligible patients. FQHC staff are enthusiastic about the potential of community partnerships to foster improved implementation - providing training and support to build these relationships will be key to fulfilling that promise.

Children with ADHD can experience a wide variety of challenges related to self-regulation, which can lead to poor educational, health, and wellness outcomes. Technological interventions, such as mobile and wearable health systems, can support data collection and reflection about health status. However, little is known about how ADHD children interpret such data. We conducted a deployment study with 10 children, aged 10 to 15, for six weeks, during which they used a smartwatch in their homes. Results from observations and interviews during this study indicate that children with ADHD can interpret their own health data, particularly in the moment. However, as ADHD children develop more autonomy, smartwatch systems may require alternatives for data reflection that are interpretable and actionable for them. This work contributes to the scholarly discourse around health data visualization, particularly in considering implications for the design of health technologies for children with ADHD.

Type 1 diabetes (T1D) is an autoimmune disease resulting in pancreatic β-cell destruction. Coxsackievirus B3 (CVB3) infection and melanoma differentiation-associated protein 5 (MDA5)-dependent antiviral responses are linked with T1D development. Mutations within IFIH1, encoding for MDA5, are correlated with T1D susceptibility, but how these mutations contribute to T1D remains unclear. Utilizing non-obese diabetic (NOD) mice lacking Ifih1 expression (KO) or containing an in-frame deletion within the ATPase site of the helicase 1 domain of MDA5 (ΔHel1), we tested the hypothesis that partial or complete loss-of-function mutations in MDA5 would delay T1D by impairing proinflammatory pancreatic macrophage and T cell responses. Spontaneous T1D developed in female NOD and KO mice similarly, but was significantly delayed in ΔHel1 mice that may be partly due to a concomitant increase in myeloid-derived suppressor cells. Interestingly, KO male mice had increased spontaneous T1D compared to NOD mice. While NOD and KO mice developed CVB3-accelerated T1D, ΔHel1 mice were protected partly due to decreased type I interferons, pancreatic-infiltrating TNF+ macrophages, IFN-γ+ CD4+ T cells, and perforin+ CD8+ T cells. Furthermore, ΔHel1 MDA5 protein had reduced ATP hydrolysis compared to wild-type MDA5. Our results suggest dampened MDA5 function delays T1D, yet loss of MDA5 promotes T1D.

Some neurodivergent people prioritize visual details over the “big picture”. While excellent attention to detail has many advantages, some contexts require the rapid integration of global and local information. A local processing style can be so strong that local details interfere with the fluid integration of global information required for processing of information rapidly displayed on user interfaces. This disconnect between context of an interaction and processing style can be termed local interference. Personalization of visual stimuli can promote a more accessible computing experience. We describe how technological interventions can support shifting of visual attention from local to global features to make them more accessible. We present two empirical studies. One study with one autistic adult revealed a significant shift in eye gaze fixation, and the other study with 20 autistic children revealed filters that visually emphasize primary aspects encouraged more global comments about image content.

Physically salient objects are thought to attract attention in natural scenes. However, research has shown that meaning maps, which capture the spatial distribution of semantically informative scene features, trump physical saliency in predicting the pattern of eye moments in natural scene viewing. Meaning maps even predict the fastest eye movements, suggesting that the brain extracts the spatial distribution of potentially meaningful scene regions very rapidly. To test this hypothesis, we applied representational similarity analysis to ERP data. The ERPs were obtained from human participants (N= 32, male and female) who viewed a series of 50 different natural scenes while performing a modified 1-back task. For each scene, we obtained a physical saliency map from a computational model and a meaning map from crowd-sourced ratings. We then used representational similarity analysis to assess the extent to which the representational geometry of physical saliency maps and meaning maps can predict the representational geometry of the neural response (the ERP scalp distribution) at each moment in time following scene onset. We found that a link between physical saliency and the ERPs emerged first (∼78 ms after stimulus onset), with a link to semantic informativeness emerging soon afterward (∼87 ms after stimulus onset). These findings are in line with previous evidence indicating that saliency is computed rapidly, while also indicating that information related to the spatial distribution of semantically informative scene elements is computed shortly thereafter, early enough to potentially exert an influence on eye movements.SIGNIFICANCE STATEMENTAttention may be attracted by physically salient objects, such as flashing lights, but humans must also be able to direct their attention to meaningful parts of scenes. Understanding how we direct attention to meaningful scene regions will be important for developing treatments for disorders of attention and for designing roadways, cockpits, and computer user interfaces. Information about saliency appears to be extracted rapidly by the brain, but little is known about the mechanisms that determine the locations of meaningful information. To address this gap, we showed people photographs of real-world scenes and measured brain activity. We found that information related to the locations of meaningful scene elements was extracted rapidly, shortly after the emergence of saliency-related information.

Lamellar phases of alkyldiacetylenes in which the alkyl chains lie parallel to the substrate represent a straightforward means for scalable 1-nm-resolution interfacial patterning. This capability has the potential for substantial impacts in nanoscale electronics, energy conversion, and biomaterials design. Polymerization is required to set the 1-nm functional patterns embedded in the monolayer, making it important to understand structure-function relationships for these on-surface reactions. Polymerization can be observed for certain monomers at the single-polymer scale using scanning probe microscopy. However, substantial restrictions on the systems that can be effectively characterized have limited utility. Here, using a new multi-scale approach, we identify a large, previously unreported difference in polymerization efficiency between the two most widely used commercial diynoic acids. We further identify a core design principle for maximizing polymerization efficiency in these on-surface reactions, generating a new monomer that also exhibits enhanced polymerization efficiency.

Influence is at the very core of physical education and sport pedagogy. Indeed, a large and growing body of work has focused on the (inter)actions of sport pedagogues which are deemed to be influen...

Hollow-core fibers offer a range of beneficial properties for high-speed optical communication applications, including low latency, low chromatic dispersion and nonlinearity. Based on a system employing a ~5-km span of hollow-core nested antiresonant nodeless fiber (NANF), we demonstrate in this paper, penalty-free Nyquist 4-ary pulse amplitude modulation transmission relative to the back-to-back at 80, 100 and 112 Gb/s over the S+C+L-bands. Furthermore, using multi-carrier direct-detection optical orthogonal frequency division multiplexing, we show that compared to a standard single-mode fiber of a similar length, the NANF exhibits a significantly better bit error rate (BER) performance at 1550 nm and offers more than 20% capacity enhancement. Consequently, up to 138.09-Gb/s capacity has been achieved at a BER threshold of 3.8×10-3 after ~5-km transmission. We conclude that the use of NANF offers a promising solution for achieving simultaneously high capacity and low latency in future short-reach optical interconnects.

Some cisgender women oppose policies granting transgender women access to women-only bathrooms. We examined whether this opposition stems from perceiving that transgender women threaten the distinctiveness of the social category “women” (gender distinctiveness threat). Cisgender women ( N = 520) read about a state bill enabling transgender women to use women’s bathrooms. Participants further read that enacting the bill would mean their state officially believes that “transgender women are real women” or “transgender rights are human rights”; in the control condition, this information was omitted. Participants reported their support for the bill and level of gender distinctiveness threat. Cisgender women who read that the bill would imply their state believes transgender women are real women (vs. transgender rights are human rights) reported lower bill support, and this effect was mediated by distinctiveness threat. Perceived threat to the distinctiveness of womanhood may help explain cisgender women’s reluctance to include transgender women in women-only spaces.

Introduced less than two decades ago, glucagon-like peptide-1 receptor agonists rapidly reshaped the field of Type 2 diabetes mellitus (T2DM) care by providing glycaemic control in tandem with weight loss. However, FDA-approved GLP-1 receptor agonists are often accompanied by nausea and emesis and, in some lean T2DM patients, by undesired anorexia. Importantly, the hypophagic and emetic effects of GLP-1 receptor agonists are caused by activation of central GLP-1 receptors. This review summarizes two different approaches to mitigate the incidence and severity of nausea and emesis related to GLP-1 receptor agonists: conjugation with vitamin B(12), or related corrin ring-containing compounds (‘corrination’), and development of dual agonists of GLP-1 receptors with glucose-dependent insulinotropic polypeptide (GIP). Such approaches could lead to the generation of GLP-1 receptor agonists with improved therapeutic efficacy, thus decreasing treatment attrition, increasing patient compliance and extending treatment to a broader population of T2DM patients. The data reviewed show that it is possible to pharmacologically separate the emetic effects of GLP-1 receptor agonists from their glucoregulatory action.

The coronavirus disease 2019 (COVID-19) pandemic is a disaster, defined as an event that suspends normal activities and threatens or causes severe, community-wide damage (Masten & Motti-Stefanidi, 2020). While all school children and their families have been impacted by COVID-19 to some degree, the burdens are disproportionately being borne by children experiencing poverty and children from minority racial and ethnic groups. In this article, we consider resilience and risk in the context of the COVID-19 pandemic by focusing on children's developing adaptive systems. When adaptive systems are functioning well, most children will demonstrate resilience to disaster. The capacity of children's adaptive systems to function well depends upon their developmental histories and the social and community resources available to them. We discuss how these factors contribute to children's adaptation and close with recommendations for communities looking to support resilience to the varied adversities of COVID-19. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

SUMMARYMechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery include changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism. These agonists also promote insulin-independent Y1-R-mediated glucose uptake in muscle tissueex vivoand more profound reductions in food intake and body weight than liraglutide when administered to diet-induced obese rats. Our findings support a role for Y1-R signaling in glucoregulation and highlight the therapeutic potential of simultaneous receptor targeting to achieve long-term benefits for millions of patients.

Background Music Therapy (MT) is an evidence-based intervention in which a music therapist uses music within a therapeutic relationship to achieve targeted goals. Studies show that MT may improve patient communication, cognition and mood, and facilitate rehabilitation by improving motor skills, particularly in those with stroke and Parkinson’s disease. We aimed to integrate MT within our geriatric multidisciplinary team (MDT) by: (1) promoting knowledge of MT among MDT staff; and (2) developing and implementing a MT referral pathway for patients. Furthermore, we aimed to assess its overall impact. Methods Music therapists delivered oral presentations and experiential learning through creative workshops, collaboration and feedback to allied health therapists in our geriatric MDT. Criteria for referrals for MT and a referral pathway were developed. Data on patients who received MT was collated. Results There were 70 referrals for MT from our MDT. 61% were female, mean age 77 years. Referral sources were occupational therapists (45%), speech therapists (34%), medical social workers (13%), physiotherapists (8%). Patients included those with stroke (41%), general medical conditions (23%), dementia (16%), Parkinson's (11%) and mental health concerns (9%). There were 16 joint MDT sessions and a mean of 5 MT sessions per patient (about 40 minutes in duration). Interventions included: Melodic Intonation Therapy (MIT), singing and vocal exercises, Rhythmic Auditory Stimulation (RAS), Musical Neglect Training (MNT), Therapeutic Instrumental Musical Performance (TIMP), reminiscence and song-writing. Overall, we identified better engagement with rehabilitation and improvements in mood, speech (voice strength and verbal fluency) and upper and lower limb co-ordination. Conclusion MT was successfully integrated into a geriatric MDT and had beneficial effects on patient mood, speech, communication and motor function. Education of MDT members was crucial in achieving appropriate MT referrals. Joint MDT’s also facilitated individualised MT interventions. Findings strongly support our model that incorporates MT within an MDT.

Background Environmental Music Therapy (EMT) uses live music played by a music therapist to enhance the surrounding environment and is increasingly used in clinical settings. Studies show that EMT may reduce anxiety, enhance wellbeing, promote better communication between patients and staff, and reduce patient perception of waiting times in hospital. We aimed to explore the benefit of EMT for older adults in a geriatric outpatient setting and on rehabilitation wards. Methods Harp music was played by a music therapist in the vicinity of ambulatory clinics and on rehabilitation wards for 4 hours per week (over a 2-day period) for 20 weeks. Music exposure on any given day was to an estimated 50 outpatients, as well as 50 people passing the vicinity or to about 30 patients on the rehabilitation ward. Music was selected and played in a dynamic process, responding to verbal and non-verbal reactions of patients, family, and staff. Voluntary responses were recorded and collated. Results There were 36 recorded responses and all reflected positively on EMT. Patients cited that the music created a welcoming space and stimulated interaction and conversation. Several patients waiting for their clinic appointment noted that it distracted from fearful expectation and was a source of comfort. Some commented that they felt more relaxed and that it reduced stress. On rehabilitation wards, patients found familiar music to be calming with nurses citing that it stimulated social interaction between patients, family and staff. Responses to EMT gave insights that resulted in patient referrals for music therapy. Conclusion Environmental music played by a music therapist was found to modify patient hospital experiences. In particular, it appeared to reduce self-perceived stress and stimulate positive social interaction and conversation. This supports the use of EMT to advance the integration of the arts for wellbeing in an acute hospital.

The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes. Specifically, our results reveal that MCH neuron Ca+2activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally-relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered to be a rare condition associated with lung neuroendocrine tumours (NET), and its natural history is poorly described. We aimed to assess the prevalence and clinicopathologic characteristics of DIPNECH in the lung NET population, and to investigate predictors of time-to-progression (TTP) and overall survival (OS).We retrospectively identified patients diagnosed with DIPNECH between April 2005 and December 2020. Clinical data were collected from medical records. The relationship between baseline characteristics and TTP and OS was analysed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazards model.Of 311 patients with well-differentiated lung NETs, 61 (20%) had DIPNECH and were included in the study. Baseline demographics described 95% female, 59% never smokers and mean body mass index 34.4 kg mDIPNECH may be more prevalent in the lung NET population than previously appreciated, especially in women. Although our results confirm that DIPNECH is predominantly an indolent disease associated with TC, 23% developed AC and these patients may warrant closer observation.

Glucagon-like peptide 1 receptor (GLP-1R) agonists decrease body weight and improve glycemic control in obesity and diabetes. Patient compliance and maximal efficacy of GLP-1 therapeutics are limited by adverse side effects, including nausea and emesis. In three different species (i.e., mice, rats, and musk shrews), we show that glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling blocks emesis and attenuates illness behaviors elicited by GLP-1R activation, while maintaining reduced food intake, body weight loss, and improved glucose tolerance. The area postrema and nucleus tractus solitarius (AP/NTS) of the hindbrain are required for food intake and body weight suppression by GLP-1R ligands and processing of emetic stimuli. Using single-nuclei RNA sequencing, we identified the cellular phenotypes of AP/NTS cells expressing GIPR and GLP-1R on distinct populations of inhibitory and excitatory neurons, with the greatest expression of GIPR in γ-aminobutyric acid-ergic neurons. This work suggests that combinatorial pharmaceutical targeting of GLP-1R and GIPR will increase efficacy in treating obesity and diabetes by reducing nausea and vomiting.

The peptide hormone amylin reduces food intake and body weight and is an attractive candidate target for novel pharmacotherapies to treat obesity. However, the short half-life of native amylin and amylin analogs like pramlintide limits these compounds’ potential utility in promoting sustained negative energy balance. Here, we evaluate the ability of the novel long-acting amylin/calcitonin receptor agonist ZP5461 to reduce feeding and body weight in rats, and also test the role of calcitonin receptors (CTRs) in the dorsal vagal complex (DVC) of the hindbrain in the energy balance effects of chronic ZP5461 administration. Acute dose-response studies indicate that systemic ZP5461 (0.5–3 nmol/kg) robustly suppresses energy intake and body weight gain in chow- and high-fat diet (HFD)-fed rats. When HFD-fed rats received chronic systemic administration of ZP5461 (1–2 nmol/kg), the compound initially produced reductions in energy intake and weight gain but failed to produce sustained suppression of intake and body weight. Using virally mediated knockdown of DVC CTRs, the ability of chronic systemic ZP5461 to promote early reductions in intake and body weight gain was determined to be mediated in part by activation of DVC CTRs, implicating the DVC as a central site of action for ZP5461. Future studies should address other dosing regimens of ZP5461 to determine whether an alternative dose/frequency of administration would produce more sustained body weight suppression.

Phosphotungestic acid (PWA) supported on mesoporous MCM-41 coated NiFe2O4 magnetic nanoparticles were prepared to be used as efficient and recyclable heterogeneous catalysts for the synthesis of coumarin and xanthene derivatives. The prepared catalysts can be easily recovered and reused for four times without significant decrease in the catalytic activity. The simple recovery of the catalyst is occurred by using an external magnet. The catalysts have notable advantages in addition to easily isolation process from the reaction medium such as easy preparation, simple procedures, high stability, well catalytic performance, low reaction time and green reaction conditions. These advantages make them very good heterogenous catalysts from an economic and environmental point of view. The catalysts were fully characterized by XRD, FT-IR, SEM, EDS, TEM, XPS, and VSM analyses. XPS confirmed the presence of inverse cubic spinel phase of NiFe2O4 and the contribution of Fe(III) − O and Ni(II) − O bonds in tetrahedral (Th) and octahedral (Oh) sites. PWA was found to be well dispersed inside and outside the pores of MCM-41 and/or NF-MCM-41 that enhanced both the surface acidity and the catalytic activity. The catalyst 55 W/NF-MCM-41-II exhibited the highest acidity (Ei = 592.4 mV) and catalytic activity toward the synthesis of 14-aryl-14H-dibenzo[a,j]xanthene (94.7%) and 7-hydroxy-4-methyl coumarin (82.1%).

Over the last two decades, optical frequency combs (OFCs) have enabled some of the most accurate measurements in physics. Distributing light from OFCs via optical fibers could make these high-accuracy measurement tools available more widely, from a few dedicated metrology laboratories to other laboratories and industry. However, the performance of distributed OFCs is strongly limited by impairments of standard single mode fiber (SMF), most notably its thermal sensitivity of chromatic dispersion, for which no compensation technique has been shown to date. To overcome this limitation, use of a new class of optical fiber is suggested here: a hollow core fiber (HCF), which offers more than an order of magnitude lesser such impairment. The measured OFC frequency stability of the optical mode and mode spacing reaches 1.8 × 10−19 and 1.5 × 10−17 at a few thousand seconds, respectively, after transmitting through 7.7 km of HCF. To the best of knowledge, this is the best ever performance for km-lengths of fiber-based OFC distribution. Besides, other HCF advantages over SMF in this application are discussed. Specifically, HCFs offer over an order of magnitude lower thermal sensitivity of propagation delay, several orders of magnitude lower optical nonlinearity, and almost ten times lower chromatic dispersion.

To investigate the role of glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists alone or combined with glucagon-like peptide-1 receptor (GLP-1R) agonists to regulate palatable food intake and the role of specific macronutrients in these preferences.To understand this regulation, we treated mice and rats on several choice diet paradigms of chow and a palatable food option with individual or dual GIPR and GLP-1R agonists.In mice, the dual agonist tirzepatide suppressed total caloric intake, while promoting the intake of chow over a high fat/sucrose diet. Surprisingly, GIPR agonism alone did not alter food choice. The food intake shift observed with tirzepatide in wild-type mice was completely absent in GLP-1R knockout mice, suggesting that GIPR signalling does not regulate food preference. Tirzepatide also selectively suppressed the intake of palatable food but not chow in a rat two-diet choice model. This suppression was specific to lipids, as GLP-1R agonist and dual agonist treatment in rats on a choice paradigm assessing individual palatable macronutrients robustly inhibited the intake of Crisco (lipid) without decreasing the intake of a sucrose (carbohydrate) solution.Decreasing preference for high-caloric, high-fat foods is a powerful action of GLP-1R and dual GIPR/GLP-1R agonist therapeutics, which may contribute to the weight loss success of these drugs.

From an environmental and economic point of view, we focused on the preparation of simple catalysts with many advantages such as simple isolation, easy preparation, high stability, and well catalytic activity. Here, we prepared MCM-41 coated NiFe2O4 magnetic nanoparticles and modified their surface with phosphotungestic acid (PWA) and then sulfate. We tested the catalysts' efficiency and reuse towards the formation of xanthene and coumarin derivatives. They can be easily recovered by a simple magnet from the reaction mixture and reused up to several runs without a high decrease in the catalytic activity. The samples have been characterized by SEM, TEM, FT-IR, XRD, VSM, and XPS. XPS indicated the presence of the inverse-cubic spinel phase of NiFe2O4 and the contribution of Fe(III) − O and Ni(II) − O bonds in tetrahedral (Th) and octahedral (Oh) sites. The results indicated the good dispersion of sulfate and PWA nanoparticles on the surface and inside NF-MCM-41 which play an important role in increasing the acidity and activity of the catalyst towards the synthesis of xanthene and coumarin derivatives. The catalyst 20S-W/NF-MCM-41-II reveals the highest acidity (Ei=586.3 mV) and yields 93.92% 14-aryl-14H-dibenzo[a, j]xanthene and 78.32% 7-hydroxy-4-methyl coumarin.