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Purpose: Our objective was to apply a user-centered design process to identify phrases, graphics, and ways of communicating numerical risks that could be used to help patients understand their cancer risk and next steps on receiving BRCA1 genetic test results (positive, negative, and variants of uncertain significance)., Methods: The first phase of the study, a user-centered design process, consisted of 4 rounds of interviews (N = 42, including 13 health care professionals and 16 patients having undergone BRCA testing). The second was a randomized, between-participants experimental study of 456 United Kingdom residents that compared the resulting reports to reports used in a United Kingdom national genomic laboratory hub. Outcomes were subjective and objective comprehension, communication efficacy, actionability, and perceived risk., Results: Subjective comprehension, communication efficacy, and actionability were all higher for the user-centered reports, with no difference in perceived risk. Comprehension of participants viewing user-centered reports was significantly better on 2 items, directionally (but not significantly) better on 6 items, and directionally (but not significantly) worse on 2 items., Conclusion: Our results imply that user-centered design is a promising approach for developing materials about complex genetic risks. We suggest wordings that are likely to lead to improved comprehension when communicating BRCA-associated risks., Competing Interests: Conflict of Interest The authors declare no conflict of interest. G.R., A.C.E.L., and A.L.J.F. are employed by the Winton Centre for Risk and Evidence Communication at the University of Cambridge, which is supported by the David & Claudia Harding Foundation. L.C. was supported by Health Education England and is employed by East and North Hertfordshire NHS Trust. Additional funding was provided by Cancer Research UK. These bodies have no financial interest in the research and had no role in the design of the study, collection/analysis of data, or decision to publish., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Guidelines recommend that genetic reports should be clear to nonspecialists, including patients. We investigated the feasibility of creating reports for cystic fibrosis carrier testing through a rapid user-centered design process that built on a previously developed generic template. We evaluated the new reports' communication efficacy and effects on comprehension against comparable reports used in current clinical practice., Methods: Thirty participants took part in three rounds of interviews. Usability problems were identified and rectified in each round. One hundred ninety-three participants took part in an evaluation of the resulting reports measuring subjective comprehension, risk probability comprehension, perceived communication efficacy, and other factors, as compared with standard reports., Results: Participants viewing the user-centered reports rated them as clearer, easier to understand, and more effective at communicating key information than standard reports. Both groups ended up with equivalent knowledge of risk probabilities, although we observed differences in how those probabilities were perceived., Conclusion: Our findings demonstrate that by starting with a patient-friendly generic report template and modifying it for specific scenarios with a rapid user-centered design process, reports can be produced that are more effective at communicating key information. The resulting reports are now being implemented into clinical care.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The paper describes a highly space-resolved characterization of the surface mechanical properties of the posterior human corneal layer (Descemet's membrane). This has been accomplished with Atomic Force Microscopy (AFM) nano-indentation by using a probe with a sharp tip geometry. Results indicate that the contact with this biological tissue in liquid occurs with no (or very low) adhesion. More importantly, under the same operating conditions, a broad distribution of penetration depth can be measured on different x-y positions of the tissue surface, indicating a high inhomogeneity of surface stiffness, not yet clearly reported in the literature. An important contribution to such inhomogeneity should be ascribed to the discontinuous nature of the collagen/proteoglycans fibers matrix tissue, as can be imaged by AFM when the tissue is semi-dry. Using classical contact mechanics calculations adapted to the specific geometry of the tetrahedral tip it has been found that the elastic modulus E of the material in the very proximity of the surface ranges from 0.23 to 2.6 kPa., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Clinical trials play a key role in advancing medical knowledge, improving patient care and promoting economic growth in Europe. We have assessed the clinical trial activity in any respiratory diseases in Europe, with a specific focus on Italy., Methods: Information from public sources (EFPIA, clinicaltrials.gov, clinicaltrialsregister. eu, AIFA) was used to describe clinical trial activity of in respiratory diseases in Europe and by country., Results: In 2015, 3908 clinical trials were reported in Europe, 386 in respiratory diseases (9.9%). Germany was the first country both as absolute number (76 trials) and as percentage within country trials (14%), followed by Poland. Spain, Italy and France were the countries with the lowest number and percentage of trials in respiratory diseases. In 2013, the Italian Drug Agency reported 9 trials with respiratory compounds in Italy (2.1% of overall trials, 12ˆ position in the therapeutic area rank), 33% in phase 2 and 66% in phase 3. No phase 1 or phase 4 trials were reported for respiratory trials. Prevalence of respiratory trials by non-profit sponsors (28.3%) was below the average for the country (38.3%)., Conclusions: Europe has a greater potential for clinical research on drugs for respiratory diseases, particularly in countries with less activity, such as Spain, France and Italy, that should identify and implement actions to increase attractiveness for clinical trials of drugs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In the last several years pharmacogenetics and pharmacogenomics have attracted the interest of the scientific community and of important pharmaceutical groups. What is the consequence for medicine and for the pharmaceutical industry? What has emerged from this investment, and what can we expect for the future? As with many new technologies, pharmacogenetics and pharmacogenomics were first adapted with much enthusiasm, and then found to require time and experience, together with sustained investment, before they could take their full place in drug discovery and development. The benefits of these technologies are now emerging, however, and they have become essential tools for the pharmaceutical industry.

New bioisoters of psoralen, obtained by replacing carbon 8 of the central benzene ring with a nitrogen, were studied from the photochemical, photobiological and phototherapeutic points of view. In particular, 4,4'-, 4',5'-dimetyl, 4,4',5'-trimethyl and 3,4,4',5'-tetramethylazapsoralen were studied. The crystal and molecular structure of 4,4',5'-trimethylazapsoralen, obtained by X ray diffraction, was also reported. Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule. When irridiated with long ultraviolet light (365 nm), the intercalated drug photoconjugates covalently to the macromolecule, forming mono- and diadducts. The photobinding rate show the following order of magnitude: 4,4',5'-trimetylazapsoralen (4,4',5'-TMAP) = 3,4,4',5'-tetramethylazapsoralen (3,4,4',5'-TMAP) greater than 4',5'-dimethylazapsoralen (4',5'-DMAP) = 4,4'-dimethylazapsoralen (4,4'-DMAP). The DNA photobinding rate of 8-methoxypsoralen (8-MOP), taken as reference compound, is similar to that of the two dimetylazapsoralens but lower than tri- and tetramethyl derivatives. The ability of azapsoralens to form cross-links in DNA is lower than that of 8-MOP. However, capacity to induce cross-links does not parallel the DNA photobinding rate; it is higher for trimethyl derivate and lower for tetramethylazapsoralen. Azapsoralens show evident antiproliferative activity. The trimethyl derivative is the most active, followed by tetrametyl, both these compounds showing activity slightly higher than that of 8-MOP. The two dimethylderivatives are less active. The mautagenic activity of azapsoralens on E. coli WP2 TM6 is lower than that of 8-MOP in the same conditions. The new compounds do not show any skin phototoxicity on guinea pig skin. On the basis of its DNA photobinding, antiproliferative activity, mutagenicity and lack of skin phototoxicity, 4,4',5'-TMAP was chosen for clinical evaluation. Clinical results obtained by topical treatment of psoriatic plaques reveal evident therapeutic effectiveness and clearing is between good and moderate, although 8-MOP, used as reference compound, is more effective.