Objective To determine the persistence of bactericidal antibody titres following immunisation with serogroup C meningococcal glycoconjugate vaccine at age 6-15 years in order to examine changes in ...persistence of antibodies with age.Design Observational study.Setting Secondary and tertiary educational institutions in the United Kingdom.Participants Healthy adolescents aged 11-20 years previously immunised between 6 and 15 years of age with one of the three serogroup C meningococcal vaccines.Intervention Serum obtained by venepuncture.Main outcome measures Percentage of participants with (rabbit complement) serum bactericidal antibody titres of at least 1:8; geometric mean titres of serogroup C meningococcal serum bactericidal antibody.Results Five years after immunisation, 84.1% (95% confidence interval 81.6% to 86.3%) of 987 participants had a bactericidal antibody titre of at least 1:8. Geometric mean titres of bactericidal antibody were significantly lower in 11-13 year olds (147, 95% confidence interval 115 to 188) than in 14-16 year olds (300, 237 to 380) and 17-20 year olds (360, 252 to 515) (P<0.0001 for both comparisons). Within these age bands, no significant difference in geometric mean titres of bactericidal antibody between recipients of the different serogroup C meningococcal vaccines was seen. More than 70% of participants had received a vaccine from one manufacturer; in this cohort, geometric mean titres were higher in those immunised at aged 10 years or above than in those immunised before the age of 10.Conclusions Higher concentrations of bactericidal antibody are seen five years after immunisation with serogroup C meningococcal vaccine at age 10 years or above than in younger age groups, possibly owing to immunological maturation. This provides support for adolescent immunisation programmes to generate sustained protection against serogroup C meningococcal disease not only for the vaccine recipients but also, through the maintenance of herd immunity, for younger children.
The objective of this research is to detect points that describe a road surface in an unclassified point cloud of the airborne laser scanning (ALS). For this purpose we use the Random Forest learning ...algorithm. The proposed methodology consists of two stages: preparation of features and supervised point cloud classification. In this approach we consider ALS points, representing only the last echo. For these points RGB, intensity, the normal vectors, their mean values and the standard deviations are provided. Moreover, local and global height variations are taken into account as components of a feature vector. The feature vectors are calculated on a basis of the 3D Delaunay triangulation. The proposed methodology was tested on point clouds with the average point density of 12 pts/m2 that represent large urban scene. The significance level of 15% was set up for a decision tree of the learning algorithm. As a result of the Random Forest classification we received two subsets of ALS points. One of those groups represents points belonging to the road network. After the classification evaluation we achieved from 90% of the overall classification accuracy. Finally, the ALS points representing roads were merged and simplified into road network polylines using morphological operations.
We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies.
In this prospective European Prostate Cancer ...Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded.
Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years.
Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.
Digital pathology has transformed the traditional pathology practice of analyzing tissue under a microscope into a computer vision workflow. Whole-slide imaging allows pathologists to view and ...analyze microscopic images on a computer monitor, enabling computational pathology. By leveraging artificial intelligence (AI) and machine learning (ML), computational pathology has emerged as a promising field in recent years. Recently, task-specific AI/ML (eg, convolutional neural networks) has risen to the forefront, achieving above-human performance in many image-processing and computer vision tasks. The performance of task-specific AI/ML models depends on the availability of many annotated training datasets, which presents a rate-limiting factor for AI/ML development in pathology. Task-specific AI/ML models cannot benefit from multimodal data and lack generalization, eg, the AI models often struggle to generalize to new datasets or unseen variations in image acquisition, staining techniques, or tissue types. The 2020s are witnessing the rise of foundation models and generative AI. A foundation model is a large AI model trained using sizable data, which is later adapted (or fine-tuned) to perform different tasks using a modest amount of task-specific annotated data. These AI models provide in-context learning, can self-correct mistakes, and promptly adjust to user feedback. In this review, we provide a brief overview of recent advances in computational pathology enabled by task-specific AI, their challenges and limitations, and then introduce various foundation models. We propose to create a pathology-specific generative AI based on multimodal foundation models and present its potentially transformative role in digital pathology. We describe different use cases, delineating how it could serve as an expert companion of pathologists and help them efficiently and objectively perform routine laboratory tasks, including quantifying image analysis, generating pathology reports, diagnosis, and prognosis. We also outline the potential role that foundation models and generative AI can play in standardizing the pathology laboratory workflow, education, and training.
Abstract This paper explores the role of artificial intelligence (AI) and the potential to launch a network of AI institutes within federal agencies for innovation and risk management. After ...providing background about changes in US economic activity and recent AI policy, we study the barriers to science and technology policy and focus on the challenge of coordination in an increasingly complex and interdependent world and how better coordination is required to manage against AI risks. We introduce the concept of a networked approach to intra-agency AI collaboration, drawing on our experience in the National Artificial Intelligence Institute (NAII) at the US Department of Veterans Affairs. Using the NAII as a case-study, we outline a decentralized approach that allows each agency to contribute and coordinate at a local level and in the areas of greatest strength offer substantial opportunity for driving innovation.
Minerals with composition (Fe,Ni)2P, are rare, though important accessory phases in iron and chondritic meteorites. The occurrence of these minerals in meteorites is believed to originate either from ...the equilibrium condensation of protoplanetary materials in solar nebulae or from the later accretion and condensation processes in the cores of parent bodies. Fe‐Ni phosphides are considered a possible candidate for a minor phase present in the Earth's core, and at least partially responsible for the observed density deficit with respect to pure iron. We report results of high‐pressure high‐temperature X‐ray diffraction experiments with synthetic barringerite (Fe2P) up to 40 GPa and 1400 K. A new phase transition to the Co2Si‐type structure has been found at 8.0 GPa, upon heating. The high‐pressure phase can be metastably quenched to ambient conditions at room temperature, and then, if heated again, transforms back to barringerite, providing an important constraint on the thermodynamic history of meteorite.
A 10.5-y-old intact female capybara (Hydrochoerus hydrochaeris) with a history of chronic weight loss was euthanized following discovery by palpation of a large intra-abdominal mass. Postmortem ...examination revealed a large, firm, tan mass expanding the uterine body and extensively adhered to the jejunum and abdominal wall. Numerous pinpoint to 3-cm diameter, tan-to-red, raised masses were present throughout the parietal peritoneum, liver, lungs, and intestinal serosa. Histologic examination of the uterine mass revealed well-differentiated smooth muscle intermixed with abundant collagen, interspersed with a highly anaplastic spindle cell population extending to the serosa; the masses in the lung, liver, and peritoneum were histologically very similar to the anaplastic uterine spindle cells. Immunohistochemical staining of the uterus and lung confirmed smooth muscle origin of the anaplastic cells. To our knowledge, leiomyosarcoma has not been reported previously in a capybara, and the widespread metastases in this case represent an unusually aggressive presentation of this rare malignancy. The animal also had an incidental dermal histiocytoma, a tumor that has also not been reported previously in this species, to our knowledge.
Background: Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several ...unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. Participants and methods: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. Results: The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G→A, 1100delC). Conclusion: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.
Multiple sclerosis (MS) is a severely debilitating disease which requires accurate and timely diagnosis. MRI is the primary diagnostic vehicle; however, it is susceptible to noise and artifact which ...can limit diagnostic accuracy. A myriad of denoising algorithms have been developed over the years for medical imaging yet the models continue to become more complex. We developed a lightweight algorithm which utilizes the image’s inherent noise via dictionary learning to improve image quality without high computational complexity or pretraining through a process known as orthogonal matching pursuit (OMP). Our algorithm is compared to existing traditional denoising algorithms to evaluate performance on real noise that would commonly be encountered in a clinical setting. Fifty patients with a history of MS who received 1.5 T MRI of the spine between the years of 2018 and 2022 were retrospectively identified in accordance with local IRB policies. Native resolution 5 mm sagittal images were selected from T2 weighted sequences for evaluation using various denoising techniques including our proposed OMP denoising algorithm. Peak signal to noise ratio (PSNR) and structural similarity index (SSIM) were measured. While wavelet denoising demonstrated an expected higher PSNR than other models, its SSIM was variable and consistently underperformed its comparators (0.94 ± 0.10). Our pilot OMP denoising algorithm provided superior performance with greater consistency in terms of SSIM (0.99 ± 0.01) with similar PSNR to non-local means filtering (NLM), both of which were superior to other comparators (OMP 37.6 ± 2.2, NLM 38.0 ± 1.8). The superior performance of our OMP denoising algorithm in comparison to traditional models is promising for clinical utility. Given its individualized and lightweight approach, implementation into PACS may be more easily incorporated. It is our hope that this technology will provide improved diagnostic accuracy and workflow optimization for Neurologists and Radiologists, as well as improved patient outcomes.
Background. The persistence of protection from meningococcal disease following immunization with serogroup C meningococcal (MenC) glycoconjugate vaccines in infancy is short-lived. The duration of ...protective immunity afforded by these vaccines in other at-risk age groups (i.e., adolescents and young adults) is not known. We evaluated the persistence of bactericidal antibodies following immunization with a MenC glycoconjugate vaccine (MenCV) in adolescents and the kinetics of immune response to a meningococcal AC plain polysaccharide vaccine (MenPS) challenge or a repeat dose of MenCV. Methods. We conducted a randomized comparative trial of 274 healthy 13–15-year-olds from whom a total of 4 blood samples were obtained (prior to administration of a dose of MenPS or MenCV, again on 2 further occasions at varying times from days 2–7 after vaccination, and finally on day 28 after vaccination. The correlate of protection was a serum bactericidal assay titer ⩾8 (with a serum bactericidal assay using human complement). Results. A serum bactericidal assay using human complement titer ⩾8 was observed in 75% of participants at baseline (mean age, 14.5 years; mean time since routine MenCV vaccination, 3.7 years). No increase in serum bactericidal assay geometric mean titers was detected until day 5 after administration of MenPS. Geometric mean titers following administration of MenCV were significantly higher than those observed following administration of MenPS, at days 5, 7, and 28. Conclusions. This study showed sustained levels of bactericidal antibodies for at least 3 years after immunization of adolescents with MenCV. After challenge of immunized adolescents with MenPS, there was no increase in serum bactericidal assay observed until day 5 after vaccination, indicating that immunological memory may be too slow to generate protection against this potentially rapidly invasive organism.
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