Experimental investigation of an axisymmetric free jet with an initially uniform velocity profile

An experimental investigation was conducted to determine the flow characteristics of a circular free helium jet having an initially uniform velocity profile. Complete velocity profiles are presented at Reynolds numbers of 1027 and 4571 at 0, 3, 6, 10, 15, and 20 nozzle diameters (where possible) from the nozzle exit. Centerline velocity decay and potential core length were obtained over a range of Reynolds numbers from 155 to 5349 at distances up to and including 25 nozzle diameters from the nozzle exit. The angles of spread associated with the diffusion of the jet downstream of the nozzle are also given. Axial jet momentum flux and entrained mass flux, at various distances downstream of the nozzle, are presented as a function of the jet Reynolds number

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state

Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix

Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), matrix metalloproteinase 9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5-HT7R and CD44 (identified as an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine remodeling, synaptic pruning, and impairment of long-term potentiation (LTP). The underlying molecular machinery involves 5-HT7R-mediated activation of MMP-9, which leads to CD44 cleavage followed by Cdc42 activation. One important physiological consequence of this interaction includes an increase in neuronal outgrowth and elongation of dendritic spines, which might have a positive effect on complex neuronal processes (e.g., reversal learning and neuronal regeneration)

The effect of sex and irritable bowel syndrome on HPA axis response and peripheral glucocorticoid receptor expression

Background & Aims: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in irritable bowel syndrome (IBS). Enhanced HPA axis responses have been associated with reduced glucocorticoid receptor (GR) mediated negative feedback inhibition. We aimed to study the effects of IBS status, sex, or presence of early adverse life events (EAL) on the cortisol response to corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH), and on GR mRNA expression in peripheral blood mononuclear cells (PBMCs). Methods: Rome III+ IBS patients and healthy controls underwent CRF (1μg/kg ovine) and ACTH (250μg) stimulation tests with serial plasma ACTH and cortisol levels measured (n=116). GR mRNA levels were measured using quantitative PCR (n=143). Area under the curve (AUC) and linear mixed effects models were used to compare ACTH and cortisol response measured across time between groups. Results: There were divergent effects of IBS on the cortisol response to ACTH by sex. In men, IBS was associated with an increased AUC (p= 0.009), but in women AUC was blunted in IBS(p=0.006). Men also had reduced GR mRNA expression (p=0.007). Cumulative exposure to EALs was associated with an increased HPA response. Lower GR mRNA was associated with increased pituitary HPA response and increased severity of overall symptoms and abdominal pain in IBS. Conclusion: This study highlights the importance of considering sex in studies of IBS and the stress response in general. Our findings also provide support for PBMC GR mRNA expression as a peripheral marker of central HPA response

Analysis of the initial-stage sintering of mechanically activated SrTiO3

The initial-stage of sintering plays a significant role in determining the final microstructure that defines the main characteristics of electroceramics materials such as functional properties. In this article non-isothermal sintering of non-activated and mechanically activated SrTiO3 samples was investigated up to 1300 °C. Dilatometric curves indicate that mechanical activation leads to an earlier onset of sintering, suggesting that it should lead to a more homogenous and denser sintered product. Analysis of the initial stage of sintering reveals that the sintering process of all examinated samples consists of two or three overlapping single-step processes, with a change in the dominant mass transport mechanism. The values of apparent activation energy of the considered single-step process exhibit a significant decrease with an increase in mechanical activation time. The values of the density of samples after isothermal sintering indicate that the final stage of sintering has not been reached by 1300 °C

Increased pain intensity is associated with greater verbal communication difficulty and increased production of speech and co-speech gestures

Effective pain communication is essential if adequate treatment and support are to be provided. Pain communication is often multimodal, with sufferers utilising speech, nonverbal behaviours (such as facial expressions), and co-speech gestures (bodily movements, primarily of the hands and arms that accompany speech and can convey semantic information) to communicate their experience. Research suggests that the production of nonverbal pain behaviours is positively associated with pain intensity, but it is not known whether this is also the case for speech and co-speech gestures. The present study explored whether increased pain intensity is associated with greater speech and gesture production during face-to-face communication about acute, experimental pain. Participants (N = 26) were exposed to experimentally elicited pressure pain to the fingernail bed at high and low intensities and took part in video-recorded semi-structured interviews. Despite rating more intense pain as more difficult to communicate (t(25) = 2.21, p = .037), participants produced significantly longer verbal pain descriptions and more co-speech gestures in the high intensity pain condition (Words: t(25) = 3.57, p = .001; Gestures: t(25) = 3.66, p = .001). This suggests that spoken and gestural communication about pain is enhanced when pain is more intense. Thus, in addition to conveying detailed semantic information about pain, speech and co-speech gestures may provide a cue to pain intensity, with implications for the treatment and support received by pain sufferers. Future work should consider whether these findings are applicable within the context of clinical interactions about pain

Analysis of the Initial-Stage Sintering of Mechanically Activated SrTiO3

The initial-stage of sintering plays a significant role in determining the final microstructure that defines the main characteristics of electroceramics materials such as functional properties. In this article non-isothermal sintering of non-activated and mechanically activated SrTiO3 samples was investigated up to 1300 degrees C. Dilatometric curves indicate that mechanical activation leads to an earlier onset of sintering, suggesting that it should lead to a more homogenous and denser sintered product. Analysis of the initial stage of sintering reveals that the sintering process of all examinated samples consists of two or three overlapping single-step processes, with a change in the dominant mass transport mechanism. The values of apparent activation energy of the considered single-step process exhibit a significant decrease with an increase in mechanical activation time. The values of the density of samples after isothermal sintering indicate that the final stage of sintering has not been reached by 1300 degrees C

A-407 Harnessing machine learning to the immuohistochemical expression of AMBRA1 and Loricin to identify non-ulcerated AJCC Stage I/II melanomas at high-risk of metastasis

Background: Precision-based personalised biomarkers able to identify both low-risk and high-risk patient subpopulations with localised cutaneous melanoma are urgently needed to guide clinical follow up and treatment stratification. We recently validated the combined immunohistochemical expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I/II melanomas as prognostic biomarker able to accurately identify genuinely low-risk patient subpopulations (NPV >96%, clinical sensitivity >95%, Ewen et al Brit J Dermatol. 2024). To further identify distinct subsets of patients with non-ulcerated AJCC stage I/II melanomas ar high risk of metastasis, the present study aimed to develop a machine learning (ML) risk-prediction model combining AMBLor ‘at -risk’ status with specific patient clinical and tumour pathological features. Methods: Using commonly and widely used ML models, ML algorithms were trained and tested using three internationally distinct retrospective-prospective cohorts of AMBLor at-risk non-ulcerated AJCC stage I/II melanomas (n=552). Results: Based on a training: test data split of 50:50, 20% of patients were defined as high-risk, with a 5-year recurrence-free survival (RFS) probability of 56% (Log-rank [Mantel-Cox) P < 0.0001, HR 6.88, 95% CI 3[PL1].03-15.63, clinical specificity 87.2%, PPV 44.4%). Further validation of the ML algorithms in a 4th independent retrospective-prospective cohort of 120 AMBLor at-risk non-ulcerated localised melanomas derived from the UK identified 24% patients as high-risk, with a 5-year RFS of 56.3% (Log-rank [Mantel-Cox) P < 0.0001, HR 7.59, 95% CI 2.94-19.6, clinical specificity 82.1%, PPV 50%). Conclusions: Through the proven negative predictive power of AMBLor with the cumulative power of prognostic clinical and pathological features these novel translationally relevant data provide an improved risk- prediction model to stratify patients with non-ulcerated localised melanomas at low or high risk of tumour recurrence thereby aiding optimal personalised patient management and treatment stratification

Ultra-processed food intake is associated with increased gastrointestinal tract symptoms and alterations in gut microbiota in patients with systemic sclerosis

BackgroundAlterations in the gastrointestinal (GI) microbiome (i.e., dysbiosis) are a feature of systemic sclerosis (SSc). Diet is a known modifier of the GI microbiome, and ultra-processed food (UPF) consumption has been associated with adverse changes in GI microbial composition. This study aimed to determine whether UPF consumption affects the GI microbiota and GI symptoms in patients with SSc.MethodsAdult SSc patients provided stool samples and completed both the Diet History Questionnaire II (DHQ-2) and the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0). Shotgun metagenomics were performed using the Illumina NovaSeq 6000 with a target depth of 10 million 150x2 sequences per sample. UPF items (N=54) on the DHQ-2 were identified using the NOVA scale of food classification, and UPF intake was calculated as gram-per-week consumption according to patient reported frequency. General linear models were created to identify differentially abundant species based on UPF consumption and to evaluate the relationship between UPF consumption and GI symptoms as measured by the GIT 2.0. These models adjusted for body mass index (BMI), current proton pump inhibitor (PPI) use, current probiotic use, current or prior immunomodulatory therapy, and presence of small intestinal bacterial overgrowth (SIBO).ResultsOf the 65 total SSc patients included, 84.6% were female. The mean age was 53.83 ± 13.19 years, and the mean BMI was 25.25 ± 4.75. The median UPF consumption was 2395.82 g/week. Increased UPF consumption was significantly associated with increased GI symptoms in our multivariate model (β=0.34; p&lt;0.01). Among 257 species analyzed, 5 bacterial species were significantly associated with UPF consumption in the multivariate models, including Limosilactobacillus fermentum (β=0.32; p&lt;0.01) and Faecalicatena fissicatena (β= -0.36; p-value&lt;0.01), while the abundance of 6 bacterial species was significantly associated with GI symptom severity after adjusting for the aforementioned covariates.ConclusionsSSc patients reporting a higher UPF consumption demonstrated alterations in GI microbial composition as well as increased GI symptoms, even after adjusting for factors known to affect the microbiota of patients with SSc. Future studies are needed to determine whether interventions aimed at lowering UPF consumption may improve GI outcomes for patients with SSc