Early lung cancer detection using spiral computed tomography and positron emission tomography

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management

Background: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. Aim: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the ‘European Registry on Helicobacter pylori management’ (Hp-EuReg). Methods: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. Results: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. Conclusions: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme

Integrative Taxonomy for Continental-Scale Terrestrial Insect Observations

Although 21st century ecology uses unprecedented technology at the largest spatio-temporal scales in history, the data remain reliant on sound taxonomic practices that derive from 18th century science. The importance of accurate species identifications has been assessed repeatedly and in instances where inappropriate assignments have been made there have been costly consequences. The National Ecological Observatory Network (NEON) will use a standardized system based upon an integrative taxonomic foundation to conduct observations of the focal terrestrial insect taxa, ground beetles and mosquitoes, at the continental scale for a 30 year monitoring program. The use of molecular data for continental-scale, multi-decadal research conducted by a geographically widely distributed set of researchers has not been evaluated until this point. The current paper addresses the development of a reference library for verifying species identifications at NEON and the key ways in which this resource will enhance a variety of user communities

High-Luminosity Large Hadron Collider (HL-LHC): Technical Design Report

The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up a new energy frontier for exploration in 2010, it has gathered a global user community of about 9000 scientists working in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its instantaneous luminosity (rate of collisions) by a factor of five beyond the original design value and the integrated luminosity (total number of collisions) by a factor ten. The LHC is already a highly complex and exquisitely optimised machine so this upgrade must be carefully conceived and will require new infrastructures (underground and on surface) and over a decade to implement. The new configuration, known as High Luminosity LHC (HL-LHC), relies on a number of key innovations that push accelerator technology beyond its present limits. Among these are cutting-edge 11–12 Tesla superconducting magnets, compact superconducting cavities for beam rotation with ultra-precise phase control, new technology and physical processes for beam collimation and 100 metre-long high-power superconducting links with negligible energy dissipation, all of which required several years of dedicated R&D effort on a global international level. The present document describes the technologies and components that will be used to realise the project and is intended to serve as the basis for the detailed engineering design of the HL-LHC

Multisite Study of Women Living With HIV's Perceived Barriers to, and Interest in, Long-Acting Injectable Antiretroviral Therapy

BACKGROUND: Adherence to antiretroviral therapy (ART) is imperative for viral suppression and reducing HIV transmission, but many people living with HIV report difficultly sustaining long-term adherence. Long-acting injectable (LAI) ART has the potential to transform HIV treatment and prevention. However, little LAI ART-related behavioral research has occurred among women, particularly outside of clinical trials. SETTING: Six Women's Interagency HIV Study sites: New York, Chicago, Washington DC, Atlanta, Chapel Hill, and San Francisco. METHODS: We conducted 59 in-depth interviews with women living with HIV across 6 Women's Interagency HIV Study sites (10 per site; 9 at Washington DC). We interviewed women who were not included in LAI ART clinical trials but who receive care at university settings that will administer LAI ART once it is approved. Interviews were recorded, transcribed, and analyzed using thematic content analysis. RESULTS: Most women enthusiastically endorsed monthly LAI ART and would prefer it over pills. The following 3 reasons emerged for this preference: (1) convenience and confidentiality, (2) avoiding daily reminders about living with HIV, and (3) believing that shots are more effective than pills. Challenges remain, however, specifically around (1) medical mistrust, (2) concerns about safety and effectiveness, (3) pill burden for HIV and other conditions, and (4) barriers to additional medical visits. CONCLUSIONS: Most women preferred LAI ART over daily pills given its benefits, including convenience, privacy, and perceived effectiveness. Future research should incorporate more women into LAI ART trials to better understand and align development with user concerns and preferences to enhance uptake

Inside-Out Regulation of ICAM-1 Dynamics in TNF-α-Activated Endothelium

Background: During transendothelial migration, leukocytes use adhesion molecules, such as ICAM-1, to adhere to the endothelium. ICAM-1 is a dynamic molecule that is localized in the apical membrane of the endothelium and clusters upon binding to leukocytes. However, not much is known about the regulation of ICAM-1 clustering and whether membrane dynamics are linked to the ability of ICAM-1 to cluster and bind leukocyte integrins. Therefore, we studied the dynamics of endothelial ICAM-1 under non-clustered and clustered conditions. Principal Findings: Detailed scanning electron and fluorescent microscopy showed that the apical surface of endothelial cells constitutively forms small filopodia-like protrusions that are positive for ICAM-1 and freely move within the lateral plane of the membrane. Clustering of ICAM-1, using anti-ICAM-1 antibody-coated beads, efficiently and rapidly recruits ICAM-1. Using fluorescence recovery after photo-bleaching (FRAP), we found that clustering increased the immobile fraction of ICAM-1, compared to non-clustered ICAM-1. This shift required the intracellular portion of ICAM-1. Moreover, biochemical assays showed that ICAM-1 clustering recruited beta-actin and filamin. Cytochalasin B, which interferes with actin polymerization, delayed the clustering of ICAM-1. In addition, we could show that cytochalasin B decreased the immobile fraction of clustered ICAM-1-GFP, but had no effect on non-clustered ICAM-1. Also, the motor protein myosin-II is recruited to ICAM-1 adhesion sites and its inhibition increased the immobile fraction of both non-clustered and clustered ICAM-1. Finally, blocking Rac1 activation, the formation of lipid rafts, myosin-II activity or actin polymerization, but not Src, reduced the adhesive function of ICAM-1, tested under physiological flow conditions. Conclusions: Together, these findings indicate that ICAM-1 clustering is regulated in an inside-out fashion through the actin cytoskeleton. Overall, these data indicate that signaling events within the endothelium are required for efficient ICAM-1-mediated leukocyte adhesio