Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects

The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell-dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti-pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes

Preliminary observations on the utilisation of pig-dung effluent for fish production

In developing Singapore where agricultural land is making way for urbanisation and industrialisation, carp culture is being looked upon from a new perspective. It is obvious that the wanton discharge of animal waste will eventually result in polluted streams, reservoirs and coastal waters. In view of the above, preliminary investigations were carried out to evaluate the use of cess-pit effluent of pig dung for carp production. Initial results indicate that the carp pond can serve as a buffer zone where organic wastes can be cheaply and profitably removed, thereby minimising the subsequent pollution of our inland and coastal waters. However, further investigations are necessary to substantiate the use of carp ponds not only for fish production but also to serve as a reservoir for the biological reduction of organic pollutants

Exploring the One Health Paradigm in Male Breast Cancer

VS conceived the manuscript. KT and GC performed the literature search and data analysis. KT, GC, SC, GC and VS drafted the manuscript and prepared Figures. All authors reviewed the manuscript.Peer reviewe

Robustness of an Artificial Intelligence Solution for Diagnosis of Normal Chest X-Rays

Purpose: Artificial intelligence (AI) solutions for medical diagnosis require thorough evaluation to demonstrate that performance is maintained for all patient sub-groups and to ensure that proposed improvements in care will be delivered equitably. This study evaluates the robustness of an AI solution for the diagnosis of normal chest X-rays (CXRs) by comparing performance across multiple patient and environmental subgroups, as well as comparing AI errors with those made by human experts. Methods: A total of 4,060 CXRs were sampled to represent a diverse dataset of NHS patients and care settings. Ground-truth labels were assigned by a 3-radiologist panel. AI performance was evaluated against assigned labels and sub-groups analysis was conducted against patient age and sex, as well as CXR view, modality, device manufacturer and hospital site. Results: The AI solution was able to remove 18.5% of the dataset by classification as High Confidence Normal (HCN). This was associated with a negative predictive value (NPV) of 96.0%, compared to 89.1% for diagnosis of normal scans by radiologists. In all AI false negative (FN) cases, a radiologist was found to have also made the same error when compared to final ground-truth labels. Subgroup analysis showed no statistically significant variations in AI performance, whilst reduced normal classification was observed in data from some hospital sites. Conclusion: We show the AI solution could provide meaningful workload savings by diagnosis of 18.5% of scans as HCN with a superior NPV to human readers. The AI solution is shown to perform well across patient subgroups and error cases were shown to be subjective or subtle in nature

Highly multimode memory in a crystal

We experimentally demonstrate the storage of 1060 temporal modes onto a thulium-doped crystal using an atomic frequency comb (AFC). The comb covers 0.93 GHz defining the storage bandwidth. As compared to previous AFC preparation methods (pulse sequences i.e. amplitude modulation), we only use frequency modulation to produce the desired optical pumping spectrum. To ensure an accurate spectrally selective optical pumping, the frequency modulated laser is self-locked on the atomic comb. Our approach is general and should be applicable to a wide range of rare-earth doped material in the context of multimode quantum memory

Macrophage coordination of the interferon lambda immune response

Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14+ monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes

A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1-3 brain metastases

<p>Abstract</p> <p>Background</p> <p>Our research group has previously published a dosimetric planning study that demonstrated that a 60 Gy/10 fractions intralesional boost with whole-brain radiotherapy (WBRT) to 30 Gy/10 fractions was biologically equivalent with a stereotactic radiosurgery (SRS) boost of 18 Gy/1 fraction with 30 Gy/10 fractions WBRT. Helical tomotherapy (HT) was found to be dosimetrically equivalent to SRS in terms of target coverage and superior to SRS in terms of normal tissue tolerance. A phase I trial has been now completed at our institution with a total of 60 enrolled patients and 48 evaluable patients. The phase II dose has been determined to be the final phase I cohort dose of 60 Gy/10 fractions.</p> <p>Methods/Design</p> <p>The objective of this clinical trial is to subject the final phase I cohort dose to a phase II assessment of the endpoints of overall survival, intracranial control (ICC) and intralesional control (ILC). We hypothesize HT would be considered unsuitable for further study if the median OS for patients treated with the HT SIB technique is degraded by 2 months, or the intracranial progression-free rates (ICC and ILC) are inferior by 10% or greater compared to the expected results with treatment by whole brain plus SRS as defined by the RTOG randomized trial. A sample size of 93 patients was calculated based on these parameters as well as the statistical assumptions of alpha = 0.025 and beta = 0.1 due to multiple statistical testing. Secondary assessments of toxicity, health-related quality-of-life, cognitive changes, and tumor response are also integrated into this research protocol.</p> <p>Discussion</p> <p>To summarize, the purpose of this phase II trial is to assess this non-invasive alternative to SRS in terms of central nervous system (CNS) control when compared to SRS historical controls. A follow-up phase III trial may be required depending on the results of this trial in order to definitively assess non-inferiority/superiority of this approach. Ultimately, the purpose of this line of research is to provide patients with metastatic disease to the brain a shorter course, dose intense, non-invasive radiation treatment with equivalent or improved CNS control/survival and health-related quality-of-life/toxicity profile when compared to SRS radiotherapy.</p> <p>Trial registration</p> <p>Clinicaltrials.gov - <a href="http://www.clinicaltrials.gov/ct2/show/NCT01543542">NCT01543542</a>.</p

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project

To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological communit

Region-specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats

Epidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender-specific remodeling of microglia in the medial prefrontal cortex (mPFC), a core brain region in anxiety-related disorders. Gender differences in microglia morphology, the higher prevalence of anxiety in women and the negative impact of anxiety in cognition, led us to specifically evaluate cognitive behavior and associated circuits (namely mPFC-dorsal hippocampus, dHIP), as well as microglia morphology in female rats prenatally exposed to dexamethasone (in utero DEX, iuDEX). We report that iuDEX impaired recognition memory and deteriorated neuronal synchronization between mPFC and dHIP. These functional deficits are paralleled by microglia hyper-ramification in the dHIP and decreased ramification in the mPFC, showing a heterogeneous remodeling of microglia morphology, both postnatally and at adulthood in different brain regions, that differently affect mood and cognition. The chronic blockade of adenosine A2A receptors (A2A R), which are core regulators of microglia morphology and physiology, ameliorated the cognitive deficits, but not the anxiety-like behavior. Notably, A2A R blockade rectified both microglia morphology in the dHIP and the lack of mPFC-dHIP synchronization, further heralding their role in cognitive function.Santa Casa da Misericórdia, Prémio Maratona da Saúde, and Centro 2020 Regional Operational Programme (CENTRO‐01‐0145‐FEDER‐000008: BrainHealth 2020) and through FCT and through FCT and COMPETE (Strategic project: UID/NEU/04539/2013 and Project POCI‐01‐0145‐FEDER‐007440 and PTDC/NEU‐NMC/4154/2014). Rita Gaspar are supported by fellowship from the Portuguese Foundation for Science and Tecnhology (PD/BD/114116/2015)info:eu-repo/semantics/publishedVersio