Applying a Precautionary Approach to Mobile Contact Tracing for COVID-19: The Value of Reversibility

The COVID-19 pandemic presents unprecedented challenges to public health decision-making. Specifically, the lack of evidence and the urgency with which a response is called for, raise the ethical challenge of assessing how much (and what kind of) evidence is required for the justification of interventions in response to the various threats we face. Here we discuss the intervention of introducing technology that aims to trace and alert contacts of infected persons-contact tracing (CT) technology. Determining whether such an intervention is proportional is complicated by complex trade-offs and feedback loops. We suggest that the resulting uncertainties necessitate a precautionary approach. On the one hand, precautionary reasons support CT technology as a means to contribute to the prevention of harms caused by alternative interventions, or COVID-19 itself. On the other hand, however, both the extent to which such technology itself present risks of serious harm, as well as its effectiveness, remain unclear. We therefore argue that a precautionary approach should put reversibility of CT technology at the forefront. We outline several practical implications

Kilometer-long ordered nanophotonic devices by preform-to-fiber fabrication

Cataloged from PDF version of article.A preform-fo-fiber approach to the fabrication of functional fiber-based devices by thermal drawing in the viscous state is presented. A macroscopic preform rod containing metallic, semiconducting, and insulating constituents in a variety of geometries and close contact produces kilometer-long novel nanostructured fibers and fiber devices. We first review the material selection criteria and then describe metal-semiconductor-metal photosensitive and thermally sensitive fibers. These flexible, lightweight, and low-cost functional fibers may pave the way for new types of fiber sensors, such as thermal sensing fabrics, artificial skin, and large-area optoelectronic screens. Next, the preform-to-fiber approach is used to fabricate spectrally tunable photodetectors that integrate a photosensitive core and a nanostructured photonic crystal structure containing a resonant cavity. An integrated, self-monitoring optical-transmission waveguide is then described that incorporates optical transport and thermal monitoring. This fiber allows one to predict power-transmission failure, which is of paramount importance if high-power optical transmission lines are to be operated safely and reliably in medical, industrial and defense applications. A hybrid electron-photon fiber consisting of a hollow core (for optical transport by means of a photonic bandgap) and metallic wires (for electron transport) is described that may be used for transporting atoms and molecules by radiation pressure. Finally, a solid microstructured fiber fabricated with a highly nonlinear chalcogenide glass enables the generation of supercontinumn light at near-infrared wavelengths

Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study

Prognostic factors for disease-free survival in patients treated before 2005 September: multivariate analysis. (DOCX 15 kb

Nectin-4: a new prognostic biomarker for efficient therapeutic targeting of primary and metastatic triple-negative breast cancer

International audienceBackground: Triple-negative breast cancers (TNBCs) are associated with a poor prognosis. In contrast to other molecular sub-types, they have no identified specific target and chemotherapy remains the only available systemic treatment. The adhesion molecule nectin-4 represents a new potential therapeutic target in different cancer models. Here, we have tested the prognos-tic value of nectin-4 expression and assessed the therapeutic efficiency of an anti-nectin 4 antibody drug conjugate (ADC) on localised and metastatic TNBC in vitro and in vivo. Materials and methods: We analysed nectin-4/PVRL4 mRNA expression in 5673 invasive breast cancers and searched for correlations with clinicopathological features including metastasis-free survival (MFS). Immunohistochemistry was carried out in 61 TNBCs and in samples of primary TNBC Patient-Derived Xenografts (PDXs). An anti-nectin-4 antibody eligible for ADC was produced and tested in vitro and in vivo in localised and metastatic TNBC PDXs. Results: High nectin-4/PVRL4 mRNA expression was associated with poor-prognosis features including the TN and basal sub-types. High PVRL4 mRNA expression showed independent negative prognostic value for MFS in multivariate analysis in TNBCs. Nectin-4 protein expression was not detected in adult healthy tissues including mammary tissue. Membranous protein expression was found in 62% of TNBCs, with strong correlation with mRNA expression. We developed an ADC (N41mab-vcMMAE) comprising a human anti-nectin-4 monoclonal antibody conjugated to monomethyl auristatin-E (MMAE). In vitro, this ADC bound to nectin-4 with high affinity and specificity and induced its internalisation as well as dose-dependent cytotoxicity on nectin-4-expressing breast cancer cell lines. In vivo, this ADC induced rapid, complete and durable responses on nectin-4-positive xenograft TNBC samples including primary tumours, metastatic lesions, and local relapses; efficiency was dependent on both the dose and the nectin-4 tumour expression level. Conclusion: Nectin-4 is both a new promising prognostic biomarker and specific therapeutic target for ADC in the very limited armamentarium against TNBC

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial)

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26–56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m−2 – doxorubicin (D) 75 mg m−2 cycle 1, C: 3 g m−2 – D: 75 mg m−2 cycle 2, C: 3 g m−2 – D: 75 mg m−2 – 5 FU 2500 mg m−2 cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4–1.04) and 0.96 (range 0.25–1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% ± 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3–9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% ± 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome. © 1999 Cancer Research Campaig

A Pandemic Instrument Can Start Turning Collective Problems into Collective Solutions by Governing the Common-Pool Resource of Antimicrobial Effectiveness

To address the complex challenge of global antimicrobial resistance (AMR), a pandemic treaty should include mechanisms that 1) equitably address the access gap for antimicrobials, diagnostic technologies, and alternative therapies; 2) equitably conserve antimicrobials to sustain effectiveness and access across time and space; 3) equitably finance the investment, discovery, development, and distribution of new technologies; and 4) equitably finance and establish greater upstream and midstream infection prevention measures globally. Biodiversity, climate, and nuclear governance offer lessons for addressing these challenges

Participants' uptake of clinical trial results: a randomised experiment

BJC OPENInternational audienceBACKGROUND: Participants are showing great interest these days in obtaining the results of clinical trials. The aim of this study was to assess patients' uptake and understanding of the results of the trial in which they have participated and the impact of a letter offering patients the possibility of consulting the trial results on a specific website. METHODS: Breast cancer patients participating in a trial on the efficacy of Trastuzumab were randomly subdivided into an Internet group (who received the letter of invitation) and a control group (who did not receive it). Among 115 HER2-positive women from 21 centres, 107 (93%) answered a self-administered questionnaire. RESULTS: Most of the patients in both groups had access to the Internet (72.0%). The majority (97.2%) stated that receiving information about the trial results would be useful, and the oncologist was the most frequently preferred information provider. The Internet group's declared uptake of the trial results was only slightly higher (47.1% vs 33.9%; P=0.166); however, they understood the results significantly more accurately (18.8% vs 5.6%; P=0.039). INTERPRETATION: Although Internet was not the respondents' preferred source of information, the possibility of using this source slightly increased the uptake and understanding of the results