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Objective Although a high‐resolution computed tomography (HRCT) scan of the chest is the gold standard test for the detection of interstitial lung disease (ILD), there is no consensus among rheumatologists regarding the use of HRCT to screen for ILD in their patients with systemic sclerosis (SSc). The aims of this study were to describe the HRCT ordering practices at SSc centers in the United States and to determine which patient characteristics are associated with HRCT performance. Methods We performed a prospective cohort study of patients with SSc enrolled in the US‐based Collaborative National Quality and Efficacy Registry (CONQUER). We performed univariate logistic regression followed by multivariable logistic regression to determine which patient characteristics were associated with HRCT performance. Results Of the 356 patients with SSc enrolled in CONQUER, 286 (80.3%) underwent HRCT at some point during their disease course. On multivariable analyses, missing total lung capacity percent predicted (odds ratio [OR] 3.26, 95% confidence interval [CI]: 1.53‐7.41, P = 0.007) was positively associated with ever having undergone HRCT, whereas a positive anti‐centromere antibody (OR 0.27, 95% CI: 0.12‐0.61, P = 0.008) and missing forced vital capacity percent predicted (OR 0.29, 95% CI: 0.10‐0.80, P = 0.005) were negatively associated with ever having undergone HRCT. There was a trend toward a positive association between crackles on pulmonary exam and ever having undergone HRCT (OR 2.28, 95% CI: 0.97‐6.05, P = 0.058), although this relationship did not reach statistical significance. Conclusion The majority of patients with SSc enrolled in CONQUER underwent HRCT. A positive anti‐centromere antibody was the key clinical variable inversely associated with performance of HRCT.

Mitigating agricultural water pollution requires changes in land management practices and the implementation of on-farm measures to tackle the principal reasons for water quality failure. However, a paucity of robust empirical evidence on the hydrological functioning of river catchments can be a major constraint on the design of effective pollution mitigation strategies at the catchment-scale. In this regard, in 2010 the UK government established the Demonstration Test Catchment (DTC) initiative to evaluate the extent to which on-farm mitigation measures can cost-effectively reduce the impacts of agricultural water pollution on river ecology while maintaining food production capacity. A central component of the DTC platform has been the establishment of a comprehensive network of automated, web-based sensor technologies to generate high-temporal resolution empirical datasets of surface water, soil water, groundwater and meteorological parameters. In this paper, we demonstrate how this high-resolution telemetry can be used to improve our understanding of hydrological functioning and the dynamics of pollutant mobilisation and transport under a range of hydrometerological and hydrogeological conditions. Furthermore, we demonstrate how these data can be used to develop conceptual models of catchment hydrogeological processes and consider the implications of variable hydrological functioning on the performance of land management changes aimed at reducing agricultural water pollution. Keywords: River, Agriculture, Soil moisture, Groundwater, Surface water, Water pollution

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1–4% of the population. The disease is more common in women and patients of African American descent and approximately one-third of patients report a family history. Obesity and smoking are known risk factors, but associations with other immune disorders, especially inflammatory bowel disease, are also recognized. The pathogenesis of HS is poorly understood and host innate or adaptive immune response, defective keratinocyte function, and the microbial environment in the hair follicle and apocrine gland have all been postulated to play a role in disease activity. While surgical interventions can be helpful to reduce disease burden, there is a high recurrence rate. Increasingly, data supports targeted immune therapy for HS, and longitudinal studies suggest benefit from these agents, both when used alone and as an adjunct to surgical treatments. The purpose of this review is to outline the current data supporting use of targeted immune therapy in HS management.

Ryanodine receptor 2 (RyR2) hyperactivity is observed in structural heart diseases that are a result of ischemia or heart failure. It causes abnormal calcium handling and calcium leaks that cause metabolic, electrical, and mechanical dysfunction, which can trigger arrhythmias. Here, we tested the antiarrhythmic potential of dantrolene (RyR inhibitor) in human hearts. Human hearts not used in transplantation were obtained, and right ventricular outflow tract (RVOT) wedges and left ventricular (LV) slices were prepared. Pseudo-ECGs were recorded to determine premature ventricular contraction (PVC) incidences. Optical mapping was performed to determine arrhythmogenic substrates. After baseline optical recordings, tissues were treated with 1) isoproterenol (250 nM), 2) caffeine (200 mM), and 3) dantrolene (2 or 10 mM). Optical recordings were obtained after each treatment. Isoproterenol and caffeine treatment increased PVC incidence, whereas dantrolene reduced the PVC burden. Isoproterenol shortened action potential duration (APD) in the RV, RVOT, and LV regions and shortened calcium transient duration (CaTD) in the LV. Caffeine further shortened APD in the RV, did not modulate APD in the RVOT, and prolonged APD in the LV. In addition, in the LV, CaTD prolongation was also observed. More importantly, adding dantrolene did not alter APD in the RV or RVOT regions but produced a trend toward APD prolongation and significant CaTD prolongation in the LV, restoring these parameters to baseline values. In conclusions, dantrolene treatment suppresses triggers and reverses arrhythmogenic substrates in the human heart and could be a novel antiarrhythmic therapy in patients with structural heart disease. [ABSTRACT FROM AUTHOR]

Objectives SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with <5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants. Methods CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0–0.49); moderate (0.50–1.00), and severe-to-very severe (1.01–3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months. Results Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment. Conclusion This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc. [ABSTRACT FROM AUTHOR]

Discussion of change and its influence on information professionals focuses on curriculum changes needed and implemented in library and information science education at Emporia State University. Topics include social context and shifts in perspective; postmodernism; dynamics of information technology and the global information economy; and a knowledge base for a professional program. (LRW)

Three hearing aid manufacturers provided custom full-shell in-the-ear hearing aids designed for maximum acoustic gain for each of three hearing-impaired adults. Full-on coupler gain curves were similar across all nine hearing aids, with individual differences producing substantial variance in insertion gain across hearing aids. (Author/DB)

Background Aortic conduit and reservoir functions can be directly measured by four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR).Methods Twenty healthy controls (10 young and 10 age-gender-matched old controls) and 20 patients with heart failure with preserved ejection fraction (HFpEF) were recruited. All had 4D flow CMR. Flow was quantified at the ascending and descending aorta levels. In addition, at the ascending aorta level, we quantified systolic flow displacement (FDs) and systolic flow reversal ratio (sFRR). The aortic conduit function was defined as the relative drop in systolic flow from the ascending to the descending aorta (∆Fs). Aortic reservoir function was defined as descending aortic diastolic stroke volume (DAo SVd).Results Both ∆Fs (R=0.51, p=0.001) and DAo SVd (R=−0.68, p=0.001) were significantly associated with ageing. Native T1 (R=0.51, p=0.001) and extracellular volume (R=0.51, p=0.001) showed maximum association with ∆Fs. ∆Fs significantly increased in HFpEF versus age-gender-matched controls (41±8% vs 52±12%, p=0.02). In multiple regression, only ∆Fs and DAo SVd were independent predictors of the estimated glomerular filtration rate (model R=0.77, p=0.0001). FDs was significantly associated with ∆Fs (R=0.4, p=0.01) and DAo SVd (R=−0.48, p=0.002), whereas sFRR was mainly associated with DAo SVd (R=−0.46, p=0.003).Conclusion Both aortic conduit and reservoir function decline with age and this decline in aortic function is also independently associated with renal functional decline. Ascending aortic turbulent flow signatures are associated with loss of aortic conduit and reservoir functions. Finally, in HFpEF, aortic conduit and reservoir function demonstrate progressive decline.Trials registration number NCT05114785.

IntroductionImmunogenic cell death (ICD) has emerged as a novel option for cancer immunotherapy. The key determinants of ICD encompass antigenicity (the presence of antigens) and adjuvanticity, which involves the release of damage-associated molecular patterns (DAMPs) and various cytokines and chemokines. CX3CL1, also known as neurotactin or fractalkine, is a chemokine involved in cellular signalling and immune cell interactions. CX3CL1 has been denoted as a “find me” signal that stimulates chemotaxis of immune cells towards dying cells, facilitating efferocytosis and antigen presentation. However, in the context of ICD, it is uncertain whether CX3CL1 is an important mediator of the effects of ICD.MethodsIn this study, we investigated the intricate role of CX3CL1 in immunogenic apoptosis induced by mitoxantrone (MTX) in cancer cells. The Luminex xMAP technology was used to quantify murine cytokines, chemokines and growth factors to identify pivotal regulatory cytokines released by murine fibrosarcoma MCA205 and melanoma B16-F10 cells undergoing ICD. Moreover, a murine tumour prophylactic vaccination model was employed to analyse the effect of CX3CL1 on the activation of an adaptive immune response against MCA205 cells undergoing ICD. Furthermore, thorough analysis of the TCGA-SKCM public dataset from 98 melanoma patients revealed the role of CX3CL1 and its receptor CX3CR1 in melanoma patients.ResultsOur findings demonstrate enhanced CX3CL1 release from apoptotic MCA205 and B16-F10 cells (regardless of the cell type) but not if they are undergoing ferroptosis or accidental necrosis. Moreover, the addition of recombinant CX3CL1 to non-immunogenic doses of MTX-treated, apoptotically dying cancer cells in the murine prophylactic tumour vaccination model induced a robust immunogenic response, effectively increasing the survival of the mice. Furthermore, analysis of melanoma patient data revealed enhanced survival rates in individuals exhibiting elevated levels of CD8+ T cells expressing CX3CR1.ConclusionThese data collectively underscore the importance of the release of CX3CL1 in eliciting an immunogenic response against dying cancer cells and suggest that CX3CL1 may serve as a key switch in conferring immunogenicity to apoptosis.

Objective: Although a high‐resolution computed tomography (HRCT) scan of the chest is the gold standard test for the detection of interstitial lung disease (ILD), there is no consensus among rheumatologists regarding the use of HRCT to screen for ILD in their patients with systemic sclerosis (SSc). The aims of this study were to describe the HRCT ordering practices at SSc centers in the United States and to determine which patient characteristics are associated with HRCT performance. Methods: We performed a prospective cohort study of patients with SSc enrolled in the US‐based Collaborative National Quality and Efficacy Registry (CONQUER). We performed univariate logistic regression followed by multivariable logistic regression to determine which patient characteristics were associated with HRCT performance. Results: Of the 356 patients with SSc enrolled in CONQUER, 286 (80.3%) underwent HRCT at some point during their disease course. On multivariable analyses, missing total lung capacity percent predicted (odds ratio [OR] 3.26, 95% confidence interval [CI]: 1.53‐7.41, P = 0.007) was positively associated with ever having undergone HRCT, whereas a positive anti‐centromere antibody (OR 0.27, 95% CI: 0.12‐0.61, P = 0.008) and missing forced vital capacity percent predicted (OR 0.29, 95% CI: 0.10‐0.80, P = 0.005) were negatively associated with ever having undergone HRCT. There was a trend toward a positive association between crackles on pulmonary exam and ever having undergone HRCT (OR 2.28, 95% CI: 0.97‐6.05, P = 0.058), although this relationship did not reach statistical significance. Conclusion: The majority of patients with SSc enrolled in CONQUER underwent HRCT. A positive anti‐centromere antibody was the key clinical variable inversely associated with performance of HRCT. [ABSTRACT FROM AUTHOR]

Aim: Interstitial lung disease (ILD) is the leading cause of disease‐related death in systemic sclerosis (SSc). Here, we assess baseline characteristics of SSc subjects with and without restrictive lung disease (RLD) in a multi‐center, US‐based registry. Methods: SSc patients within 5 years of disease onset were enrolled in the Collaborative National Quality and Efficacy Registry (CONQUER), a multi‐center US‐based registry of SSc study participants (age ≥ 18 years) enrolled at 13 expert centers. All subjects met 2013 American College of Rheumatology / European League Against Rheumatism criteria. Subjects with a pulmonary function test (PFT) at baseline before April 1, 2020 were included. High‐resolution computed tomography scan of the chest was not available to characterize ILD for all subjects. RLD was defined as forced vital capacity (FVC) <80% or total lung capacity (TLC) <80% predicted. Results: There were 160 (45%) SSc subjects characterized as having RLD. There was no significant difference in age, gender or disease duration. RLD subjects had a mean disease duration from date of first non‐Raynaud's symptom of 2.6 years and a mean FVC% predicted of 67% at baseline. In multivariable analysis, non‐White race, higher physician global health assessment and modified Medical Research Council (mMRC) dyspnea scores, were independently associated with RLD. In the subgroup of RLD subjects with ILD, ILD had a negative correlation with RNA polymerase III antibody. Conclusion: CONQUER is the largest, multi‐center, prospective cohort of early SSc patients in the US. Non‐White race was independently associated with RLD. In addition, 45% of CONQUER subjects already had RLD, highlighting the importance of screening for SSc‐ILD at initial diagnosis. [ABSTRACT FROM AUTHOR]

Nonradioactive polymerase chain reaction (PCR) may be an effective method for diagnosing fragile X syndrome in fetuses. Fragile X syndrome is a disorder linked to the X (female) chromosome, which causes mental retardation and other abnormalities. PCR was used to analyse 570 normal X chromosomes; no genetic abnormalities were found. PCR was also was used to screen 130 pregnant women with a family history of mental retardation and 24 of their family members. None of the pregnant women were carriers of the gene for fragile X syndrome, but two of their brothers were. This resulted in the identification of two new fragile X families. Among 20 pregnant women from known fragile X families, PCR identified five who were carriers. Nine fetuses with fragile X syndrome were identified by prenatal PCR testing of 28 carriers., Objective. - To develop a rapid, nonradioactive test using the polymerase chain reaction (PCR) capable of detecting full fragile X mutations, premutations, and resolving normal alleles and to apply this to prenatal diagnosis and carrier screening of pregnant women at risk for fragile X carrier status. Design. - Prenatal and blood sample PCR analysis with confirmation by direct Southern blotting and cytogenetic techniques. Setting. - Samples sent to a DNA diagnostic research laboratory at a tertiary referral center. Participants. - Pregnant women with a family history of undiagnosed mental retardation or known fragile X syndrome and controls. Results. - A rapid, nonradioactive PCR screening protocol for the fragile X mental retardation-1 gene for both normal and mutant alleles was developed. Analysis of 570 control X chromosomes showed a modal number of 30 CGG repeats (range, 12 to 52 repeats) and a calculated heterozygosity of approximately 80%. No excess of homozygosity was found, indicating the test was accurate for normal allele resolution. In addition, 150 unrelated pregnant women were screened. Within known fragile X families, five of 20 pregnant women were diagnosed as carriers. Two new fragile X families were diagnosed among relatives of 130 females with family histories of undiagnosed mental retardation, although no carriers were identified. Prenatal PCR testing of 28 carriers accurately detected nine fetuses with full mutations. Conclusions. - This rapid, nonradioactive PCR protocol allows accurate resolution of normal alleles as well as simultaneous detection of carrier alleles and full mutations. With this approach, efficient screening of pregnant women at risk for fragile X carrier status, subsequent genetic counseling of identified carriers, and reliable prenatal diagnosis can be offered.

The recent detections of CNCN and HNCCN+ are seen as further evidence of the large abundance of NCCN in the interstellar medium. The accurate determination of the abundance of these chemically related compounds from the observational spectra requires the prior calculation of collisional rate coefficients. In this work, we aimed at computing hyperfine resolved rate coefficients for the CNCN–He collisional system. First, we determined a new potential energy surface for the CNCN–He van der Waals complex from which we computed rotationally resolved excitation cross-sections for energies up to 800 cm−1 using the quantum mechanical close-coupling approach. Then, hyperfine resolved transitions between the 30 low-lying pure rotational levels of CNCN were computed for temperatures ranging from 5 to 150 K using an improved infinite order sudden approach. The analysis of the scattering results showed a propensity rule in favour of Δ j  = Δ F 1 = Δ F for the hyperfine transitions and a slight dominance of the odd Δ j transitions. Using these data, we carried out non-LTE radiative transfer calculations to simulate the excitation of CNCN in molecular clouds and to constrain the physical conditions of cold dark clouds. Preliminary results showed that the abundance of CNCN derived from observational spectra has to be revisited using these new collisional data. [ABSTRACT FROM AUTHOR]

Objective: Response to immunosuppression is highly variable in systemic sclerosis (SSc)–related interstitial lung disease (ILD). This study was undertaken to determine whether a composite serum interferon (IFN)–inducible protein score exhibits predictive significance for the response to immunosuppression in SSc‐ILD. Methods: Serum samples collected in the Scleroderma Lung Study II, a randomized controlled trial of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC), were examined. Results were validated in an independent observational cohort receiving active treatment. A composite score of 6 IFN‐inducible proteins IFNγ‐inducible 10‐kd protein, monokine induced by IFNγ, monocyte chemotactic protein 2, β2‐microglobulin, tumor necrosis factor receptor type II, and macrophage inflammatory protein 3β) was calculated, and its predictive significance for longitudinal forced vital capacity percent predicted measurements was evaluated. Results: Higher baseline IFN‐inducible protein score predicted better response over 3 to 12 months in the MMF arm (point estimate = 0.41, P = 0.001) and CYC arm (point estimate = 0.91, P = 0.009). In contrast, higher baseline C‐reactive protein (CRP) levels were predictive of a worse ILD course in both treatment arms. The predictive significance of the IFN‐inducible protein score and CRP levels remained after adjustment for baseline demographic and clinical predictors. During the second year of treatment, in which patients in the CYC arm were switched to placebo, a higher IFN‐inducible protein score at 12 months showed a trend toward predicting a worse ILD course (point estimate = −0.61, P = 0.068), while it remained predictive of better response to active immunosuppression in the MMF arm (point estimate = 0.28, P = 0.029). The predictive significance of baseline IFN‐inducible protein score was replicated in the independent cohort (rs = 0.43, P = 0.028). Conclusion: A higher IFN‐inducible protein score in SSc‐ILD is predictive of better response to immunosuppression and could potentially be used to identify patients who may derive the most benefit from MMF or CYC. [ABSTRACT FROM AUTHOR]

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Abstract Background Measurement of peak velocities is important in the evaluation of heart failure. This study compared the performance of automated 4D flow cardiac MRI (CMR) with traditional transthoracic Doppler echocardiography (TTE) for the measurement of mitral inflow peak diastolic velocities. Methods Patients with Doppler echocardiography and 4D flow cardiac magnetic resonance data were included retrospectively. An established automated technique was used to segment the left ventricular transvalvular flow using short-axis cine stack of images. Peak mitral E-wave and peak mitral A-wave velocities were automatically derived using in-plane velocity maps of transvalvular flow. Additionally, we checked the agreement between peak mitral E-wave velocity derived by 4D flow CMR and Doppler echocardiography in patients with sinus rhythm and atrial fibrillation (AF) separately. Results Forty-eight patients were included (median age 69 years, IQR 63 to 76; 46% female). Data were split into three groups according to heart rhythm. The median peak E-wave mitral inflow velocity by automated 4D flow CMR was comparable with Doppler echocardiography in all patients (0.90 ± 0.43 m/s vs 0.94 ± 0.48 m/s, P = 0.132), sinus rhythm-only group (0.88 ± 0.35 m/s vs 0.86 ± 0.38 m/s, P = 0.54) and in AF-only group (1.33 ± 0.56 m/s vs 1.18 ± 0.47 m/s, P = 0.06). Peak A-wave mitral inflow velocity results had no significant difference between Doppler TTE and automated 4D flow CMR (0.81 ± 0.44 m/s vs 0.81 ± 0.53 m/s, P = 0.09) in all patients and sinus rhythm-only groups. Automated 4D flow CMR showed a significant correlation with TTE for measurement of peak E-wave in all patients group (r = 0.73, P

Objective: Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc). Although pulmonary function tests (PFTs) are commonly used to screen for ILD in patients with SSc, studies have shown that they lack sensitivity for the detection of ILD in general SSc cohorts. This study was undertaken to assess the performance characteristics of PFTs for the detection of ILD in patients with early diffuse cutaneous SSc (dcSSc), a population at high risk for the development of ILD. Methods: We performed a retrospective cohort study of patients enrolled in the Prospective Registry of Early Systemic Sclerosis at 11 sites in the US between April 2012 and January 2019. Patients were included if they underwent spirometry and high‐resolution computed tomography (HRCT) of the chest. We calculated the performance characteristics of PFTs for the detection of ILD on HRCT. Results: The study included 212 patients, 54% of whom had radiographic ILD. For the detection of ILD on HRCT imaging, a forced vital capacity (FVC) <80% predicted had a sensitivity of 63%. The combination of FVC <80% predicted or diffusing capacity for carbon monoxide (DLco) <80% predicted improved the sensitivity to 85%. An FVC <80% predicted had a negative predictive value (NPV) of 61%, while the combination of FVC <80% predicted or DLco <80% predicted had an NPV of 70%. Conclusion: PFTs alone are an inadequate screening tool for the diagnosis of ILD in patients with early dcSSc. HRCT should be part of the ILD screening algorithm in patients with dcSSc. [ABSTRACT FROM AUTHOR]

Objectives: Determine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease.Methods: Skin biopsy RNA from 48 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated.Results: SSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression.Conclusions: Skin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design. [ABSTRACT FROM AUTHOR]

The article looks at the relationship between pneumoproteins Krebs von den Lungen (KL-6) and CCL18 and the progression and severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). According to the article, data and plasma samples from participants (ages 18-75) enrolled in the Scleroderma Lung Study (SLS) were analyzed. Baseline levels of lung glycoproteins as predictors for the progression of ILD were also considered.

AimThe aim of this evaluation was to assess the impact of introducing a model of Trauma-Informed Care (TIC), comprising weekly Power Threat Meaning Framework (PTMF) Team Formulation and weekly Psychological Stabilisation staff training, to a National Health Service (NHS) adult acute inpatient mental health unit over a four-year period.MethodA retrospective service evaluation design was employed to assess for differences in the number of incidents of self-harm, seclusion and restraint in the four-year period following the introduction of TIC, when compared to the year prior.ResultsSignificant reductions were demonstrated in the monthly number of incidents of self-harm (p < 0.01; r = 0.42), seclusion (p < 0.05; r = 0.30) and restraint (p < 0.05; d = 0.55) following the introduction of TIC.ConclusionFindings suggest that PTMF Team Formulation and Psychological Stabilisation training can contribute to significant reductions in self-harm and restrictive interventions (seclusion and restraint) on adult mental health wards. Qualitative interviews with staff and service users from the unit will support a better understanding of the mechanisms of this change. Further research, employing a randomised control trial design, could increase the validity and generalisability of findings. However, the ethical implications of withholding potentially beneficial practices from a control group would need to be considered.

Phosphorus bearing molecules have been discovered in the circumstellar and interstellar media. Modeling their abundance accurately requires computations of rate coefficients induced by collision with He and H2 (i.e., the most abundant gaseous components). These calculations may be carried out by first determining highly accurate potential energy surface (PES) and cross sections. In this paper, we present the first PES of the CP(X²Σ+)-He(¹S) van der Waals collisional complex. The ab initio interaction potential was performed using the explicitly correlated restricted coupled cluster approach with simple, double, and perturbative triple excitation (RCCSD(T)-F12) in connection with the augmented-correlation consistent-polarized valence triple-ζ Gaussian basis set (aug-cc-pVTZ). The potential presents two minima of -18.62 cm-1 and -18.72 cm-1. From the PES obtained, we have computed state-to-state excitation cross sections of CP due to collision with He for energies up to 500 cm-1. Rotational transitions involving the fine-structure levels of the CP molecule were treated with a recoupling technique based on the scattering matrix calculated with the exact quantum mechanical close coupling method. Discussions on the propensity rules between the fine-structure levels were made and we found that the Δj = ΔN transitions are favored with respect to the Δj ≠ ΔN ones. The data presented in this paper may have a great impact on the accurate determination of the CP abundance in space. [ABSTRACT FROM AUTHOR]

The potential energy surface is computed at the explicitly correlated coupled cluster with simple, second and perturbative triple excitation method (CCSD(T)–F12) in connection with the augmented–correlation consistent–polarized valence triple zeta (aug–cc–pVTZ) Gaussian basis set for the NeH+ −He system. The calculations were performed by first taking into account the vibration of the molecule and then averaging the so-obtained three-dimensional potential. From this average interaction potential, cross-sections among the 11 first rotational levels of NeH+ induced by collision with He are calculated for energies up to 4000 cm−1 using the quantum mechanical close coupling (CC) approach. Collisional rate coefficients are obtained by thermally averaging these cross-sections at low temperature (T ≤ 300 K). The propensity rules of the rotational transitions obtained in this paper are discussed and compared with those of HeH+ and ArH+ in collision with electron. This work may be helpful for the eventual investigations, both theoretical and experimental, focused to detect the key cationic noble gas hydride NeH+ in the interstellar and circumstellar media as well as in laboratory experiments. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1–4% of the population. The disease is more common in women and patients of African American descent and approximately one-third of patients report a family history. Obesity and smoking are known risk factors, but associations with other immune disorders, especially inflammatory bowel disease, are also recognized. The pathogenesis of HS is poorly understood and host innate or adaptive immune response, defective keratinocyte function, and the microbial environment in the hair follicle and apocrine gland have all been postulated to play a role in disease activity. While surgical interventions can be helpful to reduce disease burden, there is a high recurrence rate. Increasingly, data supports targeted immune therapy for HS, and longitudinal studies suggest benefit from these agents, both when used alone and as an adjunct to surgical treatments. The purpose of this review is to outline the current data supporting use of targeted immune therapy in HS management. [ABSTRACT FROM AUTHOR]

In this paper, we focus on the determination of the rotational excitation rate coefficients of the first observed molecule containing noble gas 36ArH+ isotope by He. Hence, we present the first potential energy surface (PES) of ArH+ --He van der Waals system. The interaction PES of the ArH+ (X¹ Σ)+-He(¹S) complex is calculated by the ab initio explicitly correlated coupled cluster with single, double, and perturbative triple excitation (CCSD(T)-F12) method in connection with the augmented correlation consistent triple zeta Gaussian basis (aug-cc-pVTZ). The interaction potential presents two global minima of 708.00 and 172.98 cm-1 below the ArH+ (X¹ Σ +)-He(¹S) dissociation limit. Using the PES obtained, we have computed integral inelastic cross-sections in the close-coupling approach among the first 11 rotational levels of ArH+ for energies up to 2500 cm-1. Downward rate coefficients were determined at low temperature (T ≤ 300 K). It is expected that the data worked out in this study may be beneficial for further astrophysical investigations as well as laboratory experiments. [ABSTRACT FROM AUTHOR]

There remains a debate whether the ventricular volume within prolapsing mitral valve (MV) leaflets should be included in the left ventricular (LV) end-systolic volume, and therefore factored in LV stroke volume (SV), in cardiac magnetic resonance (CMR) assessments. This study aims to compare LV volumes during end-systolic phases, with and without the inclusion of the volume of blood on the left atrial aspect of the atrioventricular groove but still within the MV prolapsing leaflets, against the reference LV SV by four-dimensional flow (4DF). A total of 15 patients with MV prolapse (MVP) were retrospectively enrolled in this study. We compared LV SV with (LV SVMVP) and without (LV SVstandard) MVP left ventricular doming volume, using 4D flow (LV SV4DF) as the reference value. Significant differences were observed when comparing LV SVstandard and LV SVMVP (p < 0.001), and between LV SVstandard and LV SV4DF (p = 0.02). The Intraclass Correlation Coefficient (ICC) test demonstrated good repeatability between LV SVMVP and LV SV4DF (ICC = 0.86, p < 0.001) but only moderate repeatability between LV SVstandard and LV SV4DF (ICC = 0.75, p < 0.01). Calculating LV SV by including the MVP left ventricular doming volume has a higher consistency with LV SV derived from the 4DF assessment. In conclusion, LV SV short-axis cine assessment incorporating MVP dooming volume can significantly improve the precision of LV SV assessment compared to the reference 4DF method. Hence, in cases with bi-leaflet MVP, we recommend factoring in MVP dooming into the left ventricular end-systolic volume to improve the accuracy and precision of quantifying mitral regurgitation.

Immunogenic cell death (ICD) is a functionally unique form of cell death that promotes a T-cell-dependent anti-tumor immune response specific to antigens originating from dying cancer cells. Many anticancer agents and strategies induce ICD, but despite their robust effects in vitro and in vivo on mice, translation into the clinic remains challenging. A major hindrance in antitumor research is the poor predictive ability of classic 2D in vitro models, which do not consider tumor biological complexity, such as the contribution of the tumor microenvironment (TME), which plays a crucial role in immunosuppression and cancer evasion. In this review, we describe different tumor models, from 2D cultures to organ-on-a-chip technology, as well as spheroids and perfusion bioreactors, all of which mimic the different degrees of the TME complexity. Next, we discuss how 3D cell cultures can be applied to study ICD and how to increase the translational potential of the ICD inducers. Finally, novel research directions are provided regarding ICD in the 3D cellular context which may lead to novel immunotherapies for cancer.

In this article, the authors attempt to determine the retention rate and benefits of Painless Punctal Plug FTMplaced in patients diagnosed with dry eye. This is a prospective, observational cohort study. Forty patients diagnosed with dry eye underwent Painless Punctal Plug F placement in the inferior puncta (80 puncta) in a private clinic from January 2010 to July 2012. Patients were then followed up monthly for seven months taking note of plug retention, spontaneous plug loss, and complications. Retention rates of patients with mean age of 58.6 years were 100% after one month, 98.75% after two months, 96.25% after three months, 95% after four months, 93.75% after five months, and 92.5% after seven months. In the 80 plugs, three plugs underwent spontaneous punctal plug loss and three plugs were removed due to local discomfort. In total, 74 out of 80 plugs remained intact after seven months of follow-up. Kaplan–Meier analysis showed that there was propensity for spontaneous punctal plug loss or plug removal in the Sjogren group as compared to the non-Sjogren group. No complications were noted such as epiphora, local inflammatory reaction, nor canalicular pyogenic granuloma except for local discomfort. This study showed that Painless Punctal Plug F has a high retention rate with the following benefits, it has one-size, fitted for small to medium puncta; extended round end which made prior dilation unnecessary and once inserted, the soft round bulb fits snugly inside the punctum preventing plug loss. [ABSTRACT FROM PUBLISHER]

This paper examines relationships between rainfall–runoff, catchment connectivity, antecedent moisture conditions and fertiliser application with nitrate-N and total phosphorus (TP) fluxes in an arable headwater catchment over three hydrological years (2012–2014). Annual precipitation totals did not vary substantially between years, yet the timing of rainfall strongly influenced runoff generation and subsequent nitrate-N and TP fluxes. The greatest nitrate-N (> 250 kg N day − 1 ) and TP (> 10 kg TP day − 1 ) fluxes only occurred when shallow groundwater was within 0.6 m of the ground surface and runoff coefficients were greater than 0.1. These thresholds were reached less frequently in 2012 due to drought recovery resulting in lower annual nitrate-N (7.4 kg N ha − 1 ) and TP (0.12 kg P ha − 1 ) fluxes in comparison with 2013 (15.1 kg N ha − 1 ; 0.21 kg P ha − 1 ). The wet winter of 2013 with elevated shallow groundwater levels led to more frequent activation of sub-surface pathways and tile drain flow. Throughout the period, dry antecedent conditions had a temporary effect in elevating TP loads. Evidence of TP source exhaustion after consecutive storm events can be attributed to the repeated depletion of temporarily connected critical source areas to the river network via impermeable road surfaces. Fertiliser application varied considerably across three years due to differences in crop rotation between farms, with annual N and P fertiliser inputs varying by up to 21% and 41%, respectively. Proportional reductions in annual riverine nitrate-N and TP loadings were not observed at the sub-catchment outlet as loadings were largely influenced by annual runoff. Nitrate loadings were slightly higher during fertiliser application, but there was little relationship between P fertiliser application and riverine TP load. These data indicate that this intensive arable catchment may be in a state of biogeochemical stationarity, whereby legacy stores of nutrients buffer against changes in contemporary nutrient inputs. [ABSTRACT FROM AUTHOR]

Pelvic mobility is essential for good pelvic organ function. Any modification may be a sign of pathology. The objective of this study was to define a methodology to quantify pelvic mobility. An analysis protocol based on an image registration technique performed on dynamic magnetic resonance imaging sequences is presented. A methodology is proposed for measuring and analysing the whole displacement field based on the contour of the four pelvic organs: the vagina, bladder, rectum and uterus. A targeted analysis of pelvic mobility can be applied in the normal, hypermobility and hypomobility context. The quantification of pelvic mobility in normal conditions allows localising fascia or ligaments involved in the static of pelvic organs. In pathological situations such as prolapse, it helps localise a suspension structure weakness. In a context of hypomobility such as deep pelvic endometriosis, it should help localise pathologic areas to provide more relevant diagnosis and treatment. When combined with conventional radiology, this analysis protocol can be applied to the diagnosis and assessment of complex pelvic pathologies to help define the most suitable surgery. Moreover, these experimental results obtained in normal and pathological cases will help build and validate a better mechanical finite element model of the pelvic system. [ABSTRACT FROM AUTHOR]