Olfaction is the primary sensory modality involved in social cognition among rodents. Eusocial naked mole-rats live in large subterranean colonies with different castes and subcastes of individuals ...showing unique behavioural profiles. Thus, these animals are constantly faced with social decisions, which are key to colony maintenance and survival. Previous evidence suggests that naked mole-rats use olfaction for colony-level and individual recognition. To explicitly test a role for olfaction in naked mole-rat social decision making, we impaired function of the main olfactory system using zinc sulphate and measured performance in three behavioural paradigms: social dominance, social recognition and olfactory preference. We report that olfactory impairment significantly affected social dominance scores but that body mass was by far the most important variable for this behaviour. We confirm that naked mole-rats perform individual-level social recognition and that they prefer familiar versus unfamiliar colony olfactory cues. Although zinc sulphate decreased chemoinvestigatory behaviour in both the social recognition and olfactory preference paradigms, animals were still able to discriminate between stimuli, demonstrating that the main olfactory system is not necessary for social decision making in this species. A role for the accessory olfactory system is implied, although additional sensory cues, particularly auditory, must also be considered.
•We examined social dominance (‘pass-overs’), social recognition and olfactory preference in naked mole-rats.•Older and heavier naked mole-rats passed over conspecifics more often.•Mole-rats distinguished between unfamiliar conspecifics in a social recognition paradigm.•Mole-rats preferred soiled bedding from their own colony versus from an unfamiliar colony.•These effects persisted following zinc sulphate treatment (a temporary anosmic agent).
Intermittent claudication is debilitating leg pain affecting older people with peripheral arterial disease, which is improved by regular walking. This study evaluated associations between ...psychosocial variables and 6-min walk distance (6MWD) to identify factors that motivate walking. A total of 142 individuals with intermittent claudication (116 males; M
= 66.9 years SD = 10.2) completed cross-sectional assessments of sociodemographics, walking treatment beliefs and intention (Theory of Planned Behaviour), illness perceptions (Revised Illness Perceptions Questionnaire), and 6MWD. Multiple linear regression was used to evaluate relationships among psychosocial variables (treatment beliefs and illness perceptions) and outcomes (walking intention and 6MWD). Theory of planned behavior constructs were associated with intention (R = .72, p < .001) and 6MWD (R = .08, p < .001). Illness perceptions were associated with 6MWD only (R = .27, p < .001). Intention (β = 0.26), treatment control (β = -0.27), personal control (β = 0.32), coherence (β = 0.18), and risk factor attributions (β = 0.22; all ps < .05) were independently associated with 6MWD. Treatment beliefs and illness perceptions associated with intention and 6MWD in people with intermittent claudication are potential intervention targets.
Natural killer (NK) cells are an innate lymphoid cell lineage characterized by their capacity to provide rapid effector functions, including cytokine production and cytotoxicity. Here, we identify ...the Ikaros family member, Aiolos, as a regulator of NK‐cell maturation. Aiolos expression is initiated at the point of lineage commitment and maintained throughout NK‐cell ontogeny. Analysis of cell surface markers representative of distinct stages of peripheral NK‐cell maturation revealed that Aiolos was required for the maturation in the spleen of CD11bhighCD27− NK cells. The differentiation block was intrinsic to the NK‐cell lineage and resembled that found in mice lacking either T‐bet or Blimp1; however, genetic analysis revealed that Aiolos acted independently of all other known regulators of NK‐cell differentiation. NK cells lacking Aiolos were strongly hyper‐reactive to a variety of NK‐cell‐mediated tumor models, yet impaired in controlling viral infection, suggesting a regulatory function for CD27− NK cells in balancing these two arms of the immune response. These data place Aiolos in the emerging gene regulatory network controlling NK‐cell maturation and function.
Synopsis
Aiolos, a member of the Ikaros family of transcription factors, regulates the differentiation of mouse natural killer (NK) cells.
NK cells constitutively express Aiolos.
Aiolos is required for final stage of NK‐cell development in the spleen.
Aiolos acts independently of the known regulators of NK‐cell maturation.
Despite their impaired maturation, NK cells lacking Aiolos show enhanced ability to control tumors.
Aiolos, a member of the Ikaros family of transcription factors, regulates the differentiation of mouse natural killer cells.
Walking treatment is recommended for improving intermittent claudication (IC), a debilitating symptom of leg pain caused by peripheral arterial disease. However, center-based exercise programs ...offered in a community or hospital setting are often not implemented or adhered to. We developed a home-delivered behavior-change intervention, MOtivating Structured walking Activity in Intermittent Claudication (MOSAIC), to increase walking in people with IC. A feasibility randomized controlled trial with nested qualitative interviews involving a subsample of trial participants was conducted. Feasibility criteria evaluated participant recruitment and retention; suitability of proposed outcome measures; and acceptability and adherence to the intervention and trial. Participants (adults aged ≥18 years diagnosed with IC identified from vascular outpatient clinics) were randomized 1:1 to receive MOSAIC treatment (two 60-minute home-based sessions and two 20-minute booster telephone calls incorporating behavior-change techniques) or an attention-control comparison. Outcomes (baseline and 16-week follow-up) included the 6-minute walking distance (meters), pedometer-assessed daily walking activity (steps/d), health-related quality of life, physical functioning, and beliefs about walking treatment, peripheral arterial disease, and self-regulatory processes. Twenty-four participants (mean age: 66.8 ± 9.4 years, 79% male) were included. Feasibility criteria achieved were recruitment rate (25%), participant retention (92%), and adherence to assigned treatment or attention-control sessions (71%). Missing data rates were <10% for all outcomes except for baseline daily walking activity (36%). The trial protocol and interventions were acceptable to participants and the clinician. In conclusion, the MOSAIC trial was feasible to conduct, with the exception of high missing pedometer data. The intervention is an acceptable approach to facilitate walking among people with IC.
•A home walking program for intermittent claudication was feasible to deliver.•The 6-minute walking distance is a feasible and clinically relevant outcome.•Strategies to reduce missing pedometer data should be used.•Patients reported acceptability and therapeutic alliance after the program.
The naked mole-rat (NMR, Heterocephalus glaber) is renowned for its eusociality and exceptionally long lifespan (> 30 y) relative to its small body size (35-40 g). A NMR phenomenon that has received ...far less attention is that females show no decline in fertility or fecundity into their third decade of life. The age of onset of reproductive decline in many mammalian species is closely associated with the number of germ cells remaining at the age of sexual maturity. We quantified ovarian reserve size in NMRs at the youngest age (6 months) when subordinate females can begin to ovulate after removal from the queen's suppression. We then compared the NMR ovarian reserve size to values for 19 other mammalian species that were previously reported. The NMR ovarian reserve at 6 months of age is exceptionally large at 108,588 ± 69,890 primordial follicles, which is more than 10-fold larger than in mammals of a comparable size. We also observed germ cell nests in ovaries from 6-month-old NMRs, which is highly unusual since breakdown of germ cell nests and the formation of primordial follicles is generally complete by early postnatal life in other mammals. Additionally, we found germ cell nests in young adult NMRs between 1.25 and 3.75 years of age, in both reproductively activated and suppressed females. The unusually large NMR ovarian reserve provides one mechanism to account for this species' protracted fertility. Whether germ cell nests in adult ovaries contribute to the NMR's long reproductive lifespan remains to be determined.
White matter hyperintensities (WMHs) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing ...WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation. MRI‐based segmentation methods are often sensitive to acquisition protocols, scanners, noise‐level, and image contrast, failing to generalize to other populations and out‐of‐distribution datasets. Given these concerns, we propose a novel Bayesian 3D convolutional neural network with a U‐Net architecture that automatically segments WMH, provides uncertainty estimates of the segmentation output for quality control, and is robust to changes in acquisition protocols. We also provide a second model to differentiate deep and periventricular WMH. Four hundred thirty‐two subjects were recruited to train the CNNs from four multisite imaging studies. A separate test set of 158 subjects was used for evaluation, including an unseen multisite study. We compared our model to two established state‐of‐the‐art techniques (BIANCA and DeepMedic), highlighting its accuracy and efficiency. Our Bayesian 3D U‐Net achieved the highest Dice similarity coefficient of 0.89 ± 0.08 and the lowest modified Hausdorff distance of 2.98 ± 4.40 mm. We further validated our models highlighting their robustness on “clinical adversarial cases” simulating data with low signal‐to‐noise ratio, low resolution, and different contrast (stemming from MRI sequences with different parameters). Our pipeline and models are available at: https://hypermapp3r.readthedocs.io.
We present a robust and efficient WMH segmentation model, which also generates an uncertainty map for quality control. In addition, we present a second model to classify dWMH and pvWMH using the initial total WMH segmentation. Our segmentation models achieved high accuracy compared to SOTA algorithms on a wide spectrum of WMH burdens, especially mild WMH. Additionally, we used an augmentation scheme to make our model robust to simulated images with SNR, low resolution, and different contrasts.
Eusocial insects often display a certain degree of task specialization, which may help maximize the efficiency of a colony. Here we tested for the presence of task specialization in a eusocial ...mammal. Naked mole-rats, Heterocephalus glaber, were videorecorded across multiple days in their home colony and in a neutral arena with an unfamiliar conspecific for determination of short-term behavioural profiles. They were also recorded in these settings across the birth of multiple litters to assess the stability of behaviour patterns over months. Pup care behaviour, working behaviour and colony defence were unevenly distributed among subordinate mole-rats. Furthermore, these behaviours were stable across days and months. Across days, age was positively related to colony defence and negatively related to pup carrying. We also tested whether behaviours were stable across contexts by observing pup care behaviour outside of the colony in a neutral arena. We further attempted to determine whether mole-rats’ behaviours were contingent on the demands of the colony by removing the most frequent performers of pup care, colony defence and work behaviour from each colony. Results from these experiments suggest that when task specialists were no longer present, remaining animals adjusted their behaviour to fill the needs of the colony. Under these circumstances, younger animals engaged in the majority of working and pup-carrying behaviour while older animals engaged in the majority of colony defence behaviours. Thus, subordinate naked mole-rats show both task specialization and task switching.
•We tested for the presence of task specialization in a eusocial mammal (the naked mole-rat).•Naked mole-rats showed specialization in colony-related tasks.•Labour, pup care and colony defence were stable within individuals across days.•These behaviours were also stable in the long term across litters.•Naked mole-rats showed task switching when specialists were removed from the colony.
Purpose: To evaluate the feasibility, preliminary diagnostic accuracy and reliability of a screening tool for developmental language disorder (DLD) in early school-age children seen in a paediatric ...primary care setting.
Method: Sixty-six children aged 6-8years attending well-child visits at a large urban paediatric clinic participated. Parents completed a five-item questionnaire and children completed a 10-item sentence repetition task. A subset of participants (n = 25) completed diagnostic testing for DLD. Exploratory cut-offs were developed for the parent questionnaire, the child sentence repetition task and the combined score.
Result: The screening tool could be reliably implemented in 2 min by personnel without specialty training. The best diagnostic accuracy measures were obtained by combining the parent questionnaire and child sentence repetition task. The tool showed strong internal consistency, but the parent and child scores showed only moderate agreement.
Conclusion: The screening tool is promising for utilisation in primary care clinical settings but should first be validated in larger and more diverse samples. Both the parent and child components of the screening contributed to the preliminary findings of high sensitivity and specificity found in this study. Screening for DLD in school age children can increase awareness of an under-recognised disorder.
IntroductionWalking exercise is a recommended but underused treatment for intermittent claudication caused by peripheral arterial disease (PAD). Addressing the factors that influence walking exercise ...may increase patient uptake of and adherence to recommended walking. The primary aim of this randomised controlled trial (RCT) is to evaluate the efficacy of a physiotherapist-led behavioural change intervention on walking ability in adults with intermittent claudication (MOtivating Structured walking Activity in people with Intermittent Claudication (MOSAIC)) in comparison with usual care.Methods and analysisThe MOSAIC trial is a two-arm, parallel-group, single-blind RCT. 192 adults will be recruited from six National Health Service Hospital Trusts. Inclusion criteria are: aged ≥50 years, PAD (Ankle Brachial Pressure Index ≤0.90, radiographic evidence or clinician report) and intermittent claudication (San Diego Claudication Questionnaire), being able and willing to participate and provide informed consent. The primary outcome is walking ability (6 min walking distance) at 3 months. Outcomes will be obtained at baseline, 3 and 6 months by an assessor blind to group allocation. Participants will be individually randomised (n=96/group, stratified by centre) to receive either MOSAIC or usual care by an independent randomisation service. Estimates of treatment effects will use an intention-to-treat framework implemented using multiple regression adjusted for baseline values and centre.Ethics and disseminationThis trial has full ethical approval (London—Bloomsbury Research Ethics Committee (17/LO/0568)). It will be disseminated via patient forums, peer-reviewed publications and conference presentations.Trial registration number ISRCTN14501418
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