Water disinfection by solar radiation : assessment and application

Edited version of the project technical report entitled: Solar ultravioletradiation : assessment and appreciation for drinking-water disinfiectio

Bio-Enhanced Neoligaments Graft Bearing FE002 Primary Progenitor Tenocytes: Allogeneic Tissue Engineering & Surgical Proofs-of-Concept for Hand Ligament Regenerative Medicine.

Hand tendon/ligament structural ruptures (tears, lacerations) often require surgical reconstruction and grafting, for the restauration of finger mechanical functions. Clinical-grade human primary progenitor tenocytes (FE002 cryopreserved progenitor cell source) have been previously proposed for diversified therapeutic uses within allogeneic tissue engineering and regenerative medicine applications. The aim of this study was to establish bioengineering and surgical proofs-of-concept for an artificial graft (Neoligaments Infinity-Lock 3 device) bearing cultured and viable FE002 primary progenitor tenocytes. Technical optimization and in vitro validation work showed that the combined preparations could be rapidly obtained (dynamic cell seeding of 10 <sup>5</sup> cells/cm of scaffold, 7 days of co-culture). The studied standardized transplants presented homogeneous cellular colonization in vitro (cellular alignment/coating along the scaffold fibers) and other critical functional attributes (tendon extracellular matrix component such as collagen I and aggrecan synthesis/deposition along the scaffold fibers). Notably, major safety- and functionality-related parameters/attributes of the FE002 cells/finished combination products were compiled and set forth (telomerase activity, adhesion and biological coating potentials). A two-part human cadaveric study enabled to establish clinical protocols for hand ligament cell-assisted surgery (ligamento-suspension plasty after trapeziectomy, thumb metacarpo-phalangeal ulnar collateral ligamentoplasty). Importantly, the aggregated experimental results clearly confirmed that functional and clinically usable allogeneic cell-scaffold combination products could be rapidly and robustly prepared for bio-enhanced hand ligament reconstruction. Major advantages of the considered bioengineered graft were discussed in light of existing clinical protocols based on autologous tenocyte transplantation. Overall, this study established proofs-of-concept for the translational development of a functional tissue engineering protocol in allogeneic musculoskeletal regenerative medicine, in view of a pilot clinical trial

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Water disinfection by solar ultraviolet radiation : assessment and applications

Based on the final project report entitled: Solar ultraviolet radiation : assessment and application for drinking-water dissinfectio

Pressure sore incidence and treatment in left ventricular assist device (LVAD)-equipped patients: Insights from a prospective series.

A left ventricular assistance device (LVAD) is indicated in patients with end-stage heart failure. Due to the non-physiologic blood flow, a LVAD may favor pressure sores with a devastating risk of infection. This work shows the prevalence and treatment of pressure sores in LVAD patients, to optimize their management. We retrospectively investigated all LVAD implantations at the Lausanne University Hospital (CHUV) from 2015 to 2019. We detected patients who developed a pressure sore and evaluated the timeline, management, and outcomes. Forty-two patients benefited from LVAD, among whom 5 (12%) developed a stage III/IV pressure sore, within a mean time of 25 days. Due to their poor overall condition, 4/5 patients were treated surgically and 1/5 conservatively. Half of the patients treated with surgery had major complications requiring reoperation. After flap coverage, the mean time to healing for patients was 6 weeks. The rapid development of deep pressure sores seen in 12% of patients may be a manifestation of the maladaptive blood flow induced by LVADs, combined with their bedridden condition. Initial signs of pressure sores should be considered seriously, as they are rapidly evolving and needing an aggressive surgical treatment whenever possible (80%). Complication rate was similar compared to standard pressure sore flap treatment. All patients benefiting from flap surgery achieved effective coverage after a mean follow-up of 24 months. No patient developed a LVAD infection. Surgery must be considered early in this population to prevent potential device infection

Shared human–robot proportional control of a dexterous myoelectric prosthesis

Myoelectric prostheses allow users to recover lost functionality by controlling a robotic device with their remaining muscle activity. Such commercial devices can give users a high level of autonomy, but still do not approach the dexterity of the intact human hand. Here we present a method to control a robotic hand, shared between user intention and robotic automation. The algorithm allows user-controlled movements when high dexterity is desired, but also assisted grasping when robustness is paramount. This combination of features is currently lacking in commercial prostheses and can greatly improve prosthesis usability. First, we design and test a myoelectric proportional controller that can predict multiple joint angles simultaneously and with high accuracy. We then implement online control with both able-bodied and amputee subjects. Finally, we present a shared control scheme in which robotic automation aids in object grasping by maximizing the contact area between the hand and the object, greatly increasing grasp success and object hold times in both a virtual and a physical environment. Our results present a viable method of prosthesis control implemented in real time, for reliable articulation of multiple simultaneous degrees of freedom

Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal women with early breast cancer: results from study BIG 1-98

Purpose To evaluate locally versus centrally assessed estrogen (ER) and progesterone (PgR) receptor status and the impact of PgR on letrozole adjuvant therapy compared with tamoxifen in postmenopausal women with early breast cancer. Patients and Methods Breast International Group (BIG) 1-98 randomly assigned 8,010 patients to four arms comparing letrozole and tamoxifen with sequences of each agent. The Central Pathology Office received material for 6,549 patients (82%), of which 79% were assessable (6,291 patients). Prognostic and predictive value of both local and central hormone receptor expression on disease-free survival (DFS) were evaluated among 3,650 assessable patients assigned to the monotherapy arms. Prognostic value and the treatment effect were estimated for centrally assessed ER and PgR expression levels using the Subpopulation Treatment Effect Pattern Plot. Results Central review confirmed 97% of tumors as hormone receptor–positive (ER and/or PgR 10%). Of 105 tumors locally ER-negative, 73 were found to have more than 10% positive cells, and eight had 1% to 9%. Of 6,100 tumors locally ER positive, 66 were found to have no staining, and 54 had only 1% to 9%. Discordance was more marked for PgR than ER. Patients with tumors reclassified centrally as ER-negative, or as hormone receptor–negative, had poor DFS. Centrally assessed ER and PgR showed prognostic value. Among patients with centrally assessed ER-expressing tumors, letrozole showed better DFS than tamoxifen, irrespective of PgR expression level. Conclusion Central review changed the assessment of receptor status in a substantial proportion of patients, and should be performed whenever possible in similar trials. PgR expression did not affect the relative efficacy of letrozole over tamoxifen