Clinical and economic outcomes of remotely delivered cognitive behaviour therapy versus treatment as usual for repeat unscheduled care users with severe health anxiety: a multi-centre randomised controlled trial

Background: Repeat users of unscheduled health care with severe health anxiety are challenging to engage in psychological help and incur high service costs. We investigated whether clinical and economic outcomes were improved by offering remote cognitive behaviour therapy using videoconferencing or telephone (RCBT) compared to treatment as usual (TAU). Methods: A single-blind, parallel group, multi-centre randomised controlled trial (RCT) was undertaken in primary and general hospital care. Participants were aged >18 years with >2 unscheduled healthcare contacts within 12 months, health anxiety > 18 on the Health Anxiety Inventory (HAI). Randomisation to RCBT or TAU was stratified by site, with allocation conveyed to a trial administrator, research assessors masked to outcome. Data were collected at baseline, 3, 6, 9 and 12 months. Primary outcome was change in HAI from baseline to six months on an intention-to-treat basis. Secondary outcomes were generalised anxiety, depression, physical symptoms, function and overall health. Health economic analysis was conducted from a health service and societal perspective.Results: 524 patients were referred and assessed for trial eligibility. Of these 470 were eligible and 156 (33%) were recruited; 78 were randomised to TAU and 78 to RCBT. Compared to TAU, RCBT significantly reduced health anxiety at 6 months maintained to 9 and 12 months (mean change difference HAI -2.81; 95% CI -5.11, -0.50; p=0.017) with significant improvements in generalised anxiety, depression and overall health at 12 months but no significant change in physical symptoms or function. RCBT was strictly dominant with a net monetary benefit of £3,164 per participant at willingness to pay threshold of £30,000. No treatment-related adverse events were reported in either group. Conclusions: RCBT may reduce health anxiety, general anxiety and depression and improve overall health with considerable reductions in health and informal care costs in repeat users of unscheduled care with severe health anxiety who have previously been difficult to engage in psychological treatment. RCBT may be an easy to implement intervention to improve clinical outcome and save costs in one group of repeat users of unscheduled care

Three Capsular Polysaccharide Synthesis-Related Glucosyltransferases, GT-1, GT-2 and WcaJ, Are Associated With Virulence and Phage Sensitivity of Klebsiella pneumoniae

Klebsiella pneumoniae (K. pneumoniae) spp. are important nosocomial and community-acquired opportunistic pathogens, which cause various infections. We observed that K. pneumoniae strain K7 abruptly mutates to rough-type phage-resistant phenotype upon treatment with phage GH-K3. In the present study, the rough-type phage-resistant mutant named K7RR showed much lower virulence than K7. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis indicated that WcaJ and two undefined glycosyltransferases (GTs)- named GT-1, GT-2- were found to be down-regulated drastically in K7RR as compared to K7 strain. GT-1, GT-2, and wcaJ are all located in the gene cluster of capsular polysaccharide (CPS). Upon deletion, even of single component, of GT-1, GT-2, and wcaJ resulted clearly in significant decline of CPS synthesis with concomitant development of GH-K3 resistance and decline of virulence of K. pneumoniae, indicating that all these three GTs are more likely involved in maintenance of phage sensitivity and bacterial virulence. Additionally, K7RR and GT-deficient strains were found sensitive to endocytosis of macrophages. Mitogen-activated protein kinase (MAPK) signaling pathway of macrophages was significantly activated by K7RR and GT-deficient strains comparing with that of K7. Interestingly, in the presence of macromolecular CPS residues (>250 KD), K7(ΔGT-1) and K7(ΔwcaJ) could still be bounded by GH-K3, though with a modest adsorption efficiency, and showed minor virulence, suggesting that the CPS residues accumulated upon deletion of GT-1 or wcaJ did retain phage binding sites as well maintain mild virulence. In brief, our study defines, for the first time, the potential roles of GT-1, GT-2, and WcaJ in K. pneumoniae in bacterial virulence and generation of rough-type mutation under the pressure of bacteriophage

“Control-Alt-Delete”: Rebooting Solutions for the E-Waste Problem

A number of efforts have been launched to solve the global electronic waste (e-waste) problem. The efficiency of e-waste recycling is subject to variable national legislation, technical capacity, consumer participation, and even detoxification. E-waste management activities result in procedural irregularities and risk disparities across national boundaries. We review these variables to reveal opportunities for research and policy to reduce the risks from accumulating e-waste and ineffective recycling. Full regulation and consumer participation should be controlled and reinforced to improve local e-waste system. Aiming at standardizing best practice, we alter and identify modular recycling process and infrastructure in eco-industrial parks that will be expectantly effective in countries and regions to handle the similar e-waste stream. Toxicity can be deleted through material substitution and detoxification during the life cycle of electronics. Based on the idea of "Control-Alt-Delete", four patterns of the way forward for global e-waste recycling are proposed to meet a variety of local situations

Image Retrieval using the Improved Double Density Contourlet Transform

A new image retrieval algorithm based on the improved double density contourlet transform(DDCT) is proposed in this paper. The improved double density contourlet transform have the property of shift invariance and non-Gaussian for the high frequency sub-bands. In order to obtain the high frequency texture feature, we design the quantization histograms using the high frequency direction sub-bands. The 0/1 quantization is used to deal with the energy matrix of high frequency sub-bands. A texture point is defined as an 8-D vector by integrating different channel values from high frequency sub-bands and the quantization histograms are computed. In order to get the texture-spatial features, the local binary pattern is used to describe the texture feature of low frequency sub-band. Then the quantization histograms and the local binary pattern (LBP) can be used to denote the texture features of the image. Experiments show that the proposed algorithm using the improved double density contourlet transform outperforms the SD algorithm based on the contourlet transform in the natural image retrieval

Contamination Transport in the Coastal Unconfined Aquifer under the Influences of Seawater Intrusion and Inland Freshwater Recharge—Laboratory Experiments and Numerical Simulations

The coupled effect of seawater intrusion and inland freshwater recharge plays an important role in contamination transport in coastal heterogeneous aquifer. In this study, the effects of seawater intrusion and inland recharge on contamination transport were investigated by conducting laboratory experiments and numerical simulations. The laboratory tests were conducted in a sand tank considering two scenarios, namely the conditions of landward and seaward hydraulic gradients. The SEAWAT software was applied for validating the contaminant transport in coastal heterogeneous aquifer. The results indicated that the simulated seawater wedge and contours of the saltwater contaminant matched the observed ones well. The length of the seawater wedge in the scenario of seaward hydraulic gradient was smaller than that in the scenario of landward hydraulic gradient, which reflected that the large quantity of inland recharge have a negative effect on the invasion process of seawater. The plume moved mainly downward in the heterogeneous unconfined aquifer for both scenarios. The pollution plume became concave at the interface between each two layers, which was because the velocity of contaminant plume migration increased gradually from the upper layer to lower layer. The migration direction of the front of the plume was consistent with the direction of hydraulic gradient, which indicated that it was influenced by the water flowing. The maximum area of plume in the scenario of seaward hydraulic gradient was slightly smaller than that in the scenario of landward hydraulic gradient. The maximum area and vertical depth of the pollutant plume were sensitive to the hydraulic conductivity, dispersivity and contamination concentration. This study was of great significance to the controlling of pollution and utilization of freshwater resources in coastal areas

Model Test Study on a Shield Tunnel Adjacent to Pile in the Sub-Clay of a Coastal Area

In this study, a model test system of shield driving adjacent to pile is realized to study the response of surrounding rock and pile induced by an advanced shield tunnel in silty clay layer in a coastal area. The function of automatic pushing and the synchronous grouting of the shield were partially simulated. Similar materials of lining, soft rock and pile, were developed. A total of 33 sets of orthogonal model tests were designed to study the progressive failure caused by excavation in silty clay and the change in stratum displacement and soil pressure; the displacement and internal force response of the pile were also analyzed. The following conclusions can be given: (1) the best grouting filling coefficient range of the shield test for the case study is 1.4 to 1.6; (2) the fitting of the experimental data to obtain the settlement through the width parameter suggests that the K value of the surrounding rock is decreased by 0.075 at least, and the K value increases with the increase in pile-tunnel distance and decreases with the increase in pile depth; and (3) the weak surrounding rock in the tunnel system can be divided into five zones according to the displacement and pressure change in soft surrounding rock and the pile response in the case study. The key condition control factor was also determined

The construction, validation and promotion of the nomogram prognosis prediction model of UCEC, and the experimental verification of the expression and knockdown of the key gene GPX4

Background: Adequate prognostic prediction of Uterine Corpus Endometrial Carcinoma (UCEC) is crucial for informing clinical decision-making. However, there is a scarcity of research on the utilization of a nomogram prognostic evaluation model that incorporates pyroptosis-related genes (PRGs) in UCEC. Methods: By analyzing data from UCEC patients in the TCGA database, four PRGs associated with prognosis were identified. Subsequently, a “risk score” was developed using these four PRGs and LASSO. Ordinary and web-based dynamic nomogram prognosis prediction models were constructed. The discrimination, calibration, clinical benefit, and promotional value of the selected GPX4 were validated. The expression level of GPX4 in UCEC cell lines was subsequently verified. The effects of GPX4 knock-down on the malignant biological behavior of UCEC cells were assessed. Results: Four key PRGs and a “risk score” were identified, with the “risk score” calculated as (−0.4323) * GPX4 + (0.2385) * GSDME + (0.0525) * NLRP2 + (−0.3299) * NOD2. The nomogram prognosis prediction model, incorporating the “risk score,” “age,” and “FIGO stage,” demonstrated moderate predictive performance (AUC >0.7), good calibration, and clinical significance for 1, 3, and 5-year survival. The web-based dynamic nomogram demonstrated significant promotional value (https://shibaolu.shinyapps.io/DynamicNomogramForUCEC/). UCEC cells exhibited abnormally elevated expression of GPX4, and the knockdown of GPX4 effectively suppressed malignant biological activities, including proliferation and migration, while inducing apoptosis. The findings from tumorigenic experiments conducted on nude mice further validated the results obtained from cellular experiments. Conclusion: Following validation, the nomogram prognosis prediction model, which relies on four pivotal PRGs, demonstrated a high degree of accuracy in forecasting the precise probability of prognosis for patients with UCEC. Additionally, the web-based dynamic nomogram exhibited considerable potential for promotion. Notably, the key gene GPX4 exhibited characteristics of a potential oncogene in UCEC, as it facilitated malignant biological behavior and impeded apoptosis

Activation of PI3K/AKT/mTOR signaling axis by UBE2S inhibits autophagy leading to cisplatin resistance in ovarian cancer

Abstract Background Epithelial ovarian cancer (OC) is the fourth leading cause of cancer-related deaths in women, with a 5-year survival rate of 30%-50%. Platinum resistance is the chief culprit for the high recurrence and mortality rates. Several studies confirm that the metabolic regulation of ubiquitinating enzymes plays a vital role in platinum resistance in OC. Methods In this study, we selected ubiquitin-conjugating enzyme E2S (UBE2S) as the candidate gene for validation. The levels of UBE2S expression were investigated using TCGA, GTEx, UALCAN, and HPA databases. In addition, the correlation between UBE2S and platinum resistance in OC was analyzed using data from TCGA. Cisplatin-resistant OC cell lines were generated and UBE2S was knocked down; the transfection efficiency was verified. Subsequently, the effects of knockdown of UBE2S on the proliferation and migration of cisplatin-resistant OC cells were examined through the CCK8, Ki-67 immunofluorescence, clone formation, wound healing, and transwell assays. In addition, the UBE2S gene was also validated in vivo by xenograft models in nude mice. Finally, the relationship between the UBE2S gene and autophagy and the possible underlying regulatory mechanism was preliminarily investigated through MDC and GFP-LC3-B autophagy detection and western blotting experiments. Most importantly, experimental validation of mTOR agonist reversion (the rescuse experiments) was also performed. Results UBE2S was highly expressed in OC at both nucleic acid and protein levels. The results of immunohistochemistry showed that the level of UBE2S expression in platinum-resistant samples was significantly higher relative to the platinum-sensitive samples. By cell transfection experiments, knocking down of the UBE2S gene was found to inhibit the proliferation and migration of cisplatin-resistant OC cells. Moreover, the UBE2S gene could inhibit autophagy by activating the PI3K/AKT/mTOR signaling pathway to induce cisplatin resistance in OC in vivo and in vitro. Conclusion In conclusion, we discovered a novel oncogene, UBE2S, which was associated with platinum response in OC, and examined its key role through bioinformatics and preliminary experiments. The findings may open up a new avenue for the evaluation and treatment of OC patients at high risk of cisplatin resistance

Theoretical study on the optical properties of polyvinylidene fluoride crystal

We report our first-principles studies on the linear and non-linear optical properties of ferroelectric polyvinylidene fluoride crystal. Calculated values of the refractive indices agree well with experiments. As regards the second-harmonic-generation coefficients, theoretical values are larger than experimental ones. Possible reasons for the discrepancy are discussed