Substitution of antibodies and receptors with molecularly imprinted polymers in enzyme-linked and fluorescent assays

A new technique for coating microtitre plates with molecularly imprinted polymers (MIP), specific for low-molecular weight analytes (epinephrine, atrazine) and proteins is presented. Oxidative polymerization was performed in the presence of template; monomers: 3-aminophenylboronic acid, 3- thiopheneboronic acid and aniline were polymerized in water and the polymers were grafted onto the polystyrene surface of the microplates. It was found that this process results in the creation of synthetic materials with antibody-like binding properties. It was shown that the MIP-coated microplates are particularly useful for assay development. The high stability of the polymers and good reproducibility of the measurements make MIP coating an attractive alternative to conventional antibodies or receptors used in ELISA

Effects of semantic relationship and preactivation on memory updating.

Semantic relationship modulates working memory (WM) processes by promoting recall but impairing recognition. Updating is a core mechanism of WM responsible for its stability and flexibility; it allows maintenance of relevant information while removing no-longer relevant one. To our knowledge, no studies specifically investigated how WM updating may benefit from the processing of semantically related material. In the current study, two experiments were run with this aim. In Experiment 1, we found an advantage for semantically related words (vs. unrelated) regardless of their association type (i.e., taxonomic or thematic). A second experiment was run boosting semantic association through preactivation. Findings replicated those of Experiment 1 suggesting that preactivation was effective and improved semantic superiority. In sum, we demonstrated that long-term semantic associations benefitted the updating process, or more generally, overall WM function. In addition, pre-activating semantic nodes of a given word appears likely a process supporting WM and updating; thus, this may be the mechanism favoring word process and memorization in a semantically related text

Passio Iohannis martyris (BHL 4333)

Critical edition of an unpublished hagiographical text, based on the three known manuscripts (Firenze, Biblioteca Nazionale Centrale, Conv. Soppr. G.5.1212; Milano, Biblioteca Nazionale Braidense, Gerli MS 26; Oxford, Bodleian Library, Canon. misc. 54)

The application of the Boolean Stochastic Generation Method to model seepage under levees in heterogeneous soils

Soil heterogeneity plays an important role in incrementing the uncertainty about the reliability of geotechnical engineering works, especially levees. The presence of thin layers of soils more permeable than the surrounding matrix significantly changes the seepage flow net below and within the dike. However, the detection of these layers is extremely difficult. Consequently, to evaluate the overall safety of dikes it may be useful to adopt stochastic computation methods. The paper presents the calibration of a seepage model of an operational river embankment subject to sand boils. The levee, located along the Adige River (South Tyrol, Italy), has been monitored since 2016. Piezometers and spot temperature sensors are installed in the lateral banks while a distributed fiber optic sensors (FOS), buried in a 350 m long trench at the toe of the levee, is used to check temperature distribution in the subground. The Boolean Stochastic Generation (BoSG) method addresses the influence of layers of material with different properties with respect of the surrounding soil. 360 soil configurations were generated for a two-dimensional groundwater flow model of the levee and confronted with the monitoring data of two piezometers. This analysis permits to identify the configuration that has effects more congruent with piezometers data, which in this case is a configuration with a major presence of lenses on the waterside respect the field-side. This evidence could guide strategies for remedial works

Bichat guidelines for the clinical management of brucellosis and bioterrorism-related brucellosis

Interest in Brucella species as a biological weapon stems from the fact that airborne transmission of the agent is possible. It is highly contagious and enters through mucous membranes such as the conjunctiva, oropharynx, respiratory tract and skin abrasions. It has been estimated that 10-100 organisms only are sufficient to constitute an infectious aerosol dose for humans. Signs and symptoms are similar in patients whatever the route of transmission and are mostly non-specific. Symptoms of patients infected by aerosol are indistinguishable from those of patients infected by other routes. Regimens containing doxycycline plus streptomycin or doxycycline plus rifampin are effective for most forms of brucellosis. Isolation of patients is not necessary. Trimethoprim-sulfamethoxazole and fluoroquinolones also have good results against Brucella, but are associated with high relapse rates when used as monotherapy. The combination of ofloxacin plus rifampicin is associated with good results. Even if there is little evidence to support its utility for post-exposure prophylaxis, doxycycline plus rifampicin is recommended for 3 to 6 weeks

Phase II study of CC-486 (oral azacitidine) in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma

BACKGROUND: Treatment options are limited for recurrent nasopharyngeal carcinoma (NPC). We report results from a phase II study of CC-486 (oral azacitidine) in advanced NPC. PATIENTS AND METHODS: Patients with locally advanced or metastatic NPC and 1-2 prior treatment regimens received CC-486 300 mg daily on days 1-14 of 21-day cycles until disease progression or unacceptable toxicity. The first 6 patients of Asian-Pacific Islander (API) ethnicity received a reduced dose of 200 mg to preserve safety and tolerability; if well tolerated, subsequent API patients received CC-486 300 mg. The study could advance to stage 2 if > 4 patients achieved a response. Co-primary end-points were overall response rate (ORR) and progression-free survival (independent review). Key secondary end-points were overall survival and safety. RESULTS: Owing to faster-than-anticipated enrolment, 36 patients, including 13 of API ethnicity, were enrolled; the median age was 54.0 years. Most patients were male (81%) and had an Eastern Cooperative Oncology Group performance status 64 1 (97%). Among 25 efficacy-evaluable patients, the ORR was 12%; the median progression-free and overall survival were 4.7 and 18.0 months, respectively. The most common grade III/IV treatment-emergent adverse events were neutropenia (33%) and febrile neutropenia (11%). Twenty-one posttreatment deaths, primarily due to progressive disease or disease complications, and 1 on-treatment death (epistaxis, unrelated to study drug) occurred. The study did not advance to stage 2. CONCLUSION: CC-486 did not show sufficient clinical activity to support further development as monotherapy in this patient population. The safety profile of CC-486 in NPC was consistent with that in other solid tumours

Digital health for optimal supportive care in oncology: benefits, limits, and future perspectives

Background Digital health provides solutions that capture patient-reported outcomes (PROs) and allows symptom monitoring and patient management. Digital therapeutics is the provision to patients of evidence-based therapeutic interventions through software applications aimed at prevention, monitoring, management, and treatment of symptoms and diseases or for treatment optimization. The digital health solutions collecting PROs address many unmet needs, including access to care and reassurance, increase in adherence and treatment efficacy, and decrease in hospitalizations. With current developments in oncology including increased availability of oral drugs and reduced availability of healthcare professionals, these solutions offer an innovative approach to optimize healthcare resource utilization. Design This scoping review clarifies the role and impact of the digital health solutions in oncology supportive care, with a view of the current segmentation according to their technical features (connection to sensors, PRO collection, remote monitoring, self-management in real time…), and identifies evidence from clinical studies published about their benefits and limitations and drivers and barriers to adoption. A qualitative summary is presented. Results Sixty-six studies were identified and included in the qualitative synthesis. Studies supported the use of 38 digital health solutions collecting ePROs and allowing remote monitoring, with benefits to patients regarding symptom reporting and management, reduction in symptom distress, decrease in unplanned hospitalizations and related costs and improved quality of life and survival. Among those 38 solutions 21 provided patient self-management with impactful symptom support, improvement of QoL, usefulness and reassurance. Principal challenges are in developing and implementing digital solutions to suit most patients, while ensuring patient compliance and adaptability for use in different healthcare systems and living environments. Conclusions There is growing evidence that digital health collecting ePROs provide benefits to patients related to clinical and health economic endpoints. These digital solutions can be integrated into routine supportive care in oncology practice to provide improved patient-centered care