The Large Hadron Collider (LHC) will be upgraded in several phases that will allow significant expansion of its physics program. The final luminosity of the accelerator is expected to exceed 5 × 1034 ...cm−2s−1, five times more than the original design value. The CMS muon system must be able to sustain a physics program after the increase of luminosity and maintain a sensitivity to electroweak physics and to TeV scale searches similar to what was achieved up to now. To cope with the corresponding increase in background rates and trigger requirements, the installation of additional sets of muon detectors based on Gas Electron Multiplier (GEM) technology, referred to as GE1/1, GE2/1 and ME0, has been planned. The installation and commissioning of the GE1/1 chambers is scheduled by 2019/20, while the GE2/1 and ME0 detectors are expected to be installed between 2023 and 2027. We present an overview of the Muon Spectrometer upgrade using the GEM technology, a description of the ongoing GE1/1 project, the production, qualification and chambers installation as well as the details of the GE2/1 and ME0 upgrades. For the latter projects, we will focus on the ongoing R&D and proposed novel solutions for the detector and electronics.
Summary
Background : Prospective trials support the role of capsule enteroscopy as an improvement in diagnosing mucosal lesions in the small bowel.
Aim : To determine the diagnostic yield and safety ...of capsule enteroscopy vs. alternative diagnostic modalities (such as push enteroscopy, small bowel follow‐through or enteroclysis) in patients with small bowel diseases.
Methods : A search for prospective studies comparing capsule enteroscopy vs. other diagnostic tests in adults was performed between 1966 and 2005. Selected articles were included in a meta‐analysis. Three analyses were run separately, all included studies and studies having occult gastrointestinal bleeding or Crohn's disease as main outcome.
Results : Seventeen studies (526 patients) met inclusion criteria. The rate difference (i.e. the absolute pooled difference in the rate of positive findings) between capsule enteroscopy and alternative modalities for small bowel disease was 41% (95% CI 35.6–45.9); 37% (95% CI 29.6–44.1) for occult gastrointestinal bleeding; and 45% (95% CI 30.9–58.0) for Crohn's disease. Failure to visualize the caecum occurred in 13%, significantly more often in occult bleeders (17%) than in patients with Crohn's disease (8%) (P < 0.006). Adverse events were recorded in 29 patients (6%). Capsule retention was more frequent in patients with Crohn's disease (3% vs. 1%, OR 4.37).
Conclusions : Capsule enteroscopy proved significantly superior to push enteroscopy and small bowel radiology in the diagnosis of ileal diseases. Capsule enteroscopy is safe, though prior radiology is still necessary to rule out small bowel strictures in patients with known or suspected Crohn's disease.
Laterally spreading tumors (LSTs) are increasingly recognized as important precursors of colorectal carcinoma. The clinical behavior of these large nonpolypoid lesions is still uncertain. The aim of ...the present study was to assess prevalence and clinico-pathological features of LSTs in a large Italian cohort of patients.
The study was a subgroup analysis of a large database of patients undergoing total colonoscopy. The database originated from a multicenter cross-sectional observational study involving 80 centers throughout Italy.
Data from 27,400 total colonoscopies were analyzed. Precancerous lesions were detected in 5609 patients. Of these, LSTs were identified in 254 patients (4.5%; 95% confidence interval CI 3.5-6.2). Granular-type LSTs (G-LSTs) accounted for 83% of the cases (211/254). LSTs were predominant in the proximal colon (154, 60.6%). A total 231 lesions were endoscopically removed, with histology being available for 242. Neoplasia was confirmed in 225 lesions (93.4%) (143 low grade adenoma, 76 high grade adenoma, and six submucosal cancer). The six cases of submucosally invasive carcinoma were diagnosed in five G-LST and one nongranular LST (NG-LST). The risk of containing advanced histology was not increased in G-LST compared with NG-LST (odds ratio OR 1.55, 95%CI 0.73-3.27); it was significantly higher in lesions with large nodules (OR 3.09, 95%CI 1.05-9.04; P = 0.041) or depressed surface (OR 4.27, 95%CI 1.24-14.61; P = 0.021).
LSTs represent approximately 5% of all precancerous colorectal lesions in the Italian population and are prevalent in the proximal colon. These lesions are no more likely to harbor advanced histology than similar-sized polypoid lesions. Large nodularity or depressed surface are risk factors for advanced histology.
ABSTRACT Deep learning (DL) has recently been proposed as a novel approach for 21cm foreground removal. Before applying DL to real observations, it is essential to assess its consistency with ...established methods, its performance across various simulation models, and its robustness against instrumental systematics. This study develops a commonly used U-Net and evaluates its performance for post-reionization foreground removal across three distinct sky simulation models based on pure Gaussian realizations, the Lagrangian perturbation theory, and the Planck sky model. Consistent outcomes across the models are achieved provided that training and testing data align with the same model. On average, the residual foreground in the U-Net reconstructed data is $\sim 10~{{\ \rm per\ cent}}$ of the signal across angular scales at the considered redshift range. Comparable results are found with traditional approaches. However, blindly using a network trained on one model for data from another model yields inaccurate reconstructions, emphasizing the need for consistent training data. The study then introduces frequency-dependent Gaussian beams and bandpass fluctuations to the test data. The network struggles to denoise data affected by ‘unexpected’ systematics without prior information. However, after re-training consistently with systematics-contaminated data, the network effectively restores its reconstruction accuracy. Our results highlight the importance of incorporating prior knowledge during network training compared with established blind methods. Our work provides critical guidelines for using DL for 21cm foreground removal, tailored to specific data attributes. Notably, it is the first time that DL has been applied to the Planck sky model being most realistic foregrounds at present.
Altering membrane protein and lipid composition is an important strategy for maintaining membrane integrity during environmental stress. Many bacterial small RNAs (sRNAs) control membrane protein ...production, but sRNA-mediated regulation of membrane fatty acid composition is less well understood. The sRNA RydC was previously shown to stabilize
(cyclopropane fatty acid synthase) mRNA, resulting in higher levels of cyclopropane fatty acids in the cell membrane. Here, we report that additional sRNAs, ArrS and CpxQ, also directly regulate
posttranscriptionally. RydC and ArrS act through masking an RNase E cleavage site in the
mRNA 5' untranslated region (UTR), and both sRNAs posttranscriptionally activate
In contrast, CpxQ binds to a different site in the
mRNA 5' UTR and represses
expression. Alteration of membrane lipid composition is a key mechanism for bacteria to survive low-pH environments, and we show that
translation increases in an sRNA-dependent manner when cells are subjected to mild acid stress. This work suggests an important role for sRNAs in the acid stress response through regulation of
mRNA.
Small RNAs (sRNAs) in bacteria are abundant and play important roles in posttranscriptional regulation of gene expression, particularly under stress conditions. Some mRNAs are targets for regulation by multiple sRNAs, each responding to different environmental signals. Uncovering the regulatory mechanisms governing sRNA-mRNA interactions and the relevant conditions for these interactions is an ongoing challenge. In this study, we discovered that multiple sRNAs control membrane lipid composition by regulating stability of a single mRNA target. The sRNA-dependent regulation occurred in response to changing pH and was important for cell viability under acid stress conditions. This work reveals yet another aspect of bacterial physiology controlled at the posttranscriptional level by sRNA regulators.
Background
The choice of how to repair inguinal hernias in adolescents has historically been a matter of experience and differed between pediatric surgeons who traditionally performed a high ligation ...of the sac and general surgeons who typically perform a repair using mesh. This up-to-date review thoroughly examines the subject and discusses the suitability of both types of repairs in this unique age group.
Methods
A 20-year Pub Med search was performed for the following terms: adolescent hernia repair including reports of mesh hernia repair in adolescents and postoperative complications including chronic inguinal pain and recurrences.
Results
The evidence in the literature suggests that while there appears to be no difference between the two types of repairs with regards to recurrence and complications, changes in the pelvic floor physiology in adolescents suggest that a selective, individualized approach can be recommended depending on the size and nature of the presenting pathology.
Conclusions
A selective approach to the inguinal hernia in adolescent patients based on the size of the defect appears justified.
The aim of this study was to assess the prevalence of nonpolypoid lesions (NPLs) in Italy and their risk of containing neoplasia or advanced histology.
This was a multicenter cross-sectional ...observational study on consecutive patients undergoing total colonoscopy over a 3-month period in 80 Italian centers.
In all, 27,400 total colonoscopies were analyzed. Cancer was diagnosed in 801 patients (2.9 %). A total of 6553 precancerous lesions were detected in 5609 patients. Of these, 4154 patients (74.1 %) had polypoid lesions and 1455 patients (25.9 %) had NPLs. Therefore, the prevalence of NPLs was 5.3 % (95 %CI 5.0 - 5.6). NPLs larger than 10 mm were detected in 254 patients (17.5 %). NPLs were more predominant in the proximal colon (OR 2.92, 95 %CI 2.56 - 3.43; P < 0.0001 vs. polypoid lesions). Neoplastic tissue was diagnosed in 79.0 % and advanced histology (high-grade intraepithelial neoplasia or more) in 20.9 % of resected lesions. The risk of advanced histology was similar for polypoid and nonpolypoid lesions when adjusted for size. Depressed lesions had the highest risk of advanced histology (OR 10.56, 95 %CI 6.02 - 18.55; P < 0.0000 vs. flat-elevated). Age was an independent predictor of both neoplasia and advanced histology ( P = 0.0001).
NPLs are relatively common in the Italian population, with a prevalence similar to that in other Western series. NPLs are not more aggressive than polypoid lesions, except for those with depressed morphology.
Bacterial spot is a disease that affects tomato worldwide reducing its yield and quality. It is caused by different
Xanthomonas
spp., among which is
Xanthomonas vesicatoria
. Copper-based ...bactericides are generally used to control this disease, although nowadays sustainable strategies are being searched to efficiently replace their use. Our aim was to select native bacteria from tomato rhizosphere with biocontrol properties against
X. vesicatoria
. We selected, characterized, and identified three novel strains, two closely related to
Bacillus velezensis
(VMA11p and VM05) and one closely related to
Pseudomonas soli
(VMAP1), that in vitro antagonized
X. vesicatoria.
We evaluated the efficacy of the three rhizobacteria and their cell-free supernatants to control bacterial spot using the model tomato-
X. vesicatoria
in plants grown in pots, in greenhouse conditions. Bacterial suspensions of VMA11p and VMAP1, applied to the soil by irrigation, significantly (
P
< 0.05) reduced bacterial spot severity by 53.9% and 44.2%, respectively. Nevertheless, the most effective strategy to control bacterial spot was achieved using the cell-free supernatant produced by VMA11p, VM05 or VMAP1 applied as foliar spray, which significantly (
P
< 0.05) reduced the severity of the disease by 98.5%, 94.2% and 75.2%, respectively. None of the treatments reduced the growth of tomato plants. Our results suggest that the use of these novel strains of
Bacillus
and
Pseudomonas
and/or their metabolic products could be used for the development of biocontrol strategies for the management of bacterial spot in tomato.
Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of ...genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.
Vitamin D (VD) deficiency is a hallmark of obesity and vascular dysfunction. We sought to test the hypothesis that VD deficiency may contribute to obesity-related vascular dysfunction by inducing ...adipokine hypomethylation and augmented expression. To this end, we collected blood and adipose tissues (ATs) from a cohort of 77 obese participants who were classified as having mild, moderate, or severe VD deficiency. The body composition, vascular reactivity, cardiometabolic profiles, and DNA methylation of 94 inflammation-related adipokines were measured. Our results show that higher degrees of VD deficiency were associated with lower DNA methylation and induced the expression of inflammatory adipokines such as B-cell lymphoma 6 (
), C-X-C Motif Chemokine Ligand 8 (
), histone deacetylase 5 (
), interleukin 12A (
), and nuclear factor κB (
) in the ATs. They were also associated with higher BMI and total and visceral fat mass, impaired insulin sensitivity and lipid profiles, AT hypoxia, and higher concentrations of circulating inflammatory markers. Moderate and severe VD deficiency correlated with impaired vasoreactivity of the brachial artery and AT-isolated arterioles, reduced nitric oxide generation, and increased arterial stiffness. In a multivariate regression analysis, the VD deficiency level strongly predicted the adipokine methylation score, systemic inflammation, and microvascular dysfunction. In conclusion, our findings suggest that VD deficiency is a possible contributor to obesity-related adipokine hypomethylation, inflammation, and vascular dysfunction.
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