The potential of digital platforms to facilitate the diffusion of diversification strategies in agriculture

The agricultural landscape of Switzerland is dominated by industrialized but struggling milk production. Producers are facing ever-falling prices, environmental changes and increasing requirements for state supports. Facing these challenges, some farmers have developed their own products for niche markets, adopted rare or ancient breeds or demonstrated the capacity to adopt income-generating innovations. The diversification of agricultural production on farms and within whole regional landscapes has further advantages than just income diversification. It offers adaptation and buffer capacity in case of economic crisis or environmental changes and it makes the agro-ecosystem more resistant to pests and diseases and distributes risks. However, the majority of farms still encounters barriers in changing crops and diversifying. Interviews with producers in this study revealed that the main challenges are the lack of technical information about rare crops and breeds, the need to identify adapted crops and equipment to the location and the personal motivations that require an entrepreunarial or risk-taker personality. Information technologies and particularly new tools in the area of social networking could play an important role in increasing access to information and connections between peers, even internationally, and deserve more attention in the transition to sustainable agriculture. Interviews with market actors revealed multiple potentials for niche products, but also the need for increased availability of market information to producers. Social media are also starting to be used for this purpose. This study thus looked into the potential of multi-stakeholder online platforms and the role of key actors for the diffusion of innovation and niche products in agriculture and identified current limitations where efforts could be put to increase support to diversifying producers

Bekämpfung von Fusarien mit antifungalen Pflanzenprodukten und deren Effekte auf den Mykotoxin-Gehalt von Weizen

Fusarium graminearum (FG) is the most prevalent Fusarium Head Blight (FHB) fungus in Switzerland. In conventional agriculture, fungicides are used to reduce the risk of FHB infection and mycotoxin contamination of wheat. As an alternative for organic wheat production, we examined plant-based products that showed antifungal effects from our previous late blight field trials. In bioassays, the effect of these antifungal plant preparations (APP) was screened against FG. In 2006 and 2008, the most active APP, Rheum palmatum, Frangula alnus and preparations of Galla chinensis as well as a plant substance (PSX), were used as FHB control agents in field trials with artificial FG infections. In both years, FG incidence and deoxynivalenol content were significantly reduced by the APP. In 2006, the reduction was in the same dimension as applications with Pronto Plus®, a fungicide mixture of tebuconazole and spiroxamine

Predictive factors for preterm delivery under rural conditions in post-tsunami Banda Aceh

Objective: To assess the risk for preterm deliveries <37 week of gestation and associated prevalence of vaginal infection in a rural setting after the tsunami in Banda Aceh, Indonesia. Methods: Wet mount microscopy, vaginal pH and vaginal swabs for microbiological culture were collected in pregnant women during the 2nd trimester from February to June of 2005 in four temporary outpatient clinics and the patients were followed up until delivery. Results: One hundred and fifty-nine pregnant patients were screened. Sixty-two could be followed up until delivery. Thirty-nine (62.9%) delivered at term and 23 (37.1%) delivered prematurely. Significant risk factors for preterm delivery were a history of preterm delivery and group B streptococcus infection. Increased vaginal pH alone had no significant influence on preterm delivery, although there was a trend. Conclusion: The rate of preterm delivery was high in this cohort. We suggest risk stratification for preterm delivery in rural conditions by performing a vaginal pH and wet mount microscopy. If either is suspect we suggest collecting a vaginal swab for microbiological culture for targeted treatment. Patients with a history of preterm delivery are at increased risk and should be monitored closely

Impact of breast cancer family history on tumor detection and tumor size in women newly-diagnosed with invasive breast cancer

This study evaluated the impact of family history (FH) on tumor detection, the patient's age and tumor size at diagnosis in breast cancer (BC). Furthermore, we investigated whether the impact of FH on these features was dependent on degree of relationship, number of relatives with a BC history, or the age of the affected relative at the time that her BC was diagnosed. Out of the entire cohort (n=1,037), 244 patients (23.5%) had a positive FH; 159 (15.3%) had first-degree relatives affected with BC and 85 patients (8.2%) had second-degree affected relatives. Compared to women who had no BC-affected relatives, the tumors of women who had positive FH were more often found by radiological breast examination (RBE: 31.7%/27.2%, p=0.008), and they were smaller (general tumor size: 21.8mm/26.4mm, p=0.003; size of tumors found by breast self-examination (BSE): 26.1mm/30.6mm, p=0.041). However, this positive effect of increased use of BC screening and smaller tumor sizes was only observed in patients whose first-degree relatives were affected (comparison with second-degree affected relatives: RBE: 43.8%/24.7%; odds ratio 2.38, p=0.007; general tumor size: 19.3mm/26.3mm; mean difference (MD) −6.9, p=0.025; tumor size found by BSE: 22.5mm/31.0mm; MD −8.5, p=0.044). When more second-degree relatives or older relatives were diagnosed with BC, the tumors of these patients were similarly often detected by RBE (relationship: 24.7%/27.2%, p=0.641; age: 33.7%/27.2%, p=0.177) and had similar tumor sizes (general size: 26.3mm/26.4mm, p=0.960; BSE: 31.0mm/30.6mm, p=0.902) as those of women without a FH. Women with a positive FH generally use mammography screening more often and perceive changes in the breast earlier than women without such history. The increased awareness of BC risk decreases if the relationship is more distant

MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies

Cancer patients with advanced disease are characterized by intrinsic challenges in predicting drug response patterns, often leading to ineffective treatment. Current clinical practice for treatment decision-making is commonly based on primary or secondary tumour biopsies, yet when disease progression accelerates, tissue biopsies are not performed on a regular basis. It is in this context that liquid biopsies may offer a unique window to uncover key vulnerabilities, providing valuable information about previously underappreciated treatment opportunities. Here, we present MyCTC chip, a novel microfluidic device enabling the isolation, culture and drug susceptibility testing of cancer cells derived from liquid biopsies. Cancer cell capture is achieved through a label-free, antigen-agnostic enrichment method, and it is followed by cultivation in dedicated conditions, allowing on-chip expansion of captured cells. Upon growth, cancer cells are then transferred to drug screen chambers located within the same device, where multiple compounds can be tested simultaneously. We demonstrate MyCTC chip performance by means of spike-in experiments with patient-derived breast circulating tumour cells, enabling >95% capture rates, as well as prospective processing of blood from breast cancer patients and ascites fluid from patients with ovarian, tubal and endometrial cancer, where sensitivity to specific chemotherapeutic agents was identified. Together, we provide evidence that MyCTC chip may be used to identify personalized drug response patterns in patients with advanced metastatic disease and with limited treatment opportunities

Norwalk Virus–specific Binding to Oyster Digestive Tissues

Specific binding of virus to oysters can selectively concentrate a human pathogen

Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort

Tamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds are considered infeasible. Therefore, we aim to validate the association between Z-endoxifen concentration and tamoxifen treatment outcomes, and identify a Z-endoxifen concentration threshold of tamoxifen efficacy, using pharmacometric modeling and simulation. As a first step, the CYP2D6 Endoxifen Percentage Activity Model (CEPAM) cohort was created by pooling data from 28 clinical studies (&gt; 7,000 patients) with measured endoxifen plasma concentrations. After cleaning, data from 6,083 patients were used to develop a nonlinear mixed-effect (NLME) model for tamoxifen and Z-endoxifen pharmacokinetics that includes a conversion factor to allow inclusion of studies that measured total endoxifen but not Z-endoxifen. The final parent-metabolite NLME model confirmed the primary role of CYP2D6, and contributions from body weight, CYP2C9 phenotype, and co-medication with CYP2D6 inhibitors, on Z-endoxifen pharmacokinetics. Future work will use the model to simulate Z-endoxifen concentrations in patients receiving single agent tamoxifen treatment within large prospective clinical trials with long-term survival to identify the Z-endoxifen concentration threshold below which tamoxifen is less efficacious. Identification of this concentration threshold would allow personalized tamoxifen treatment to improve outcomes in patients with hormone receptor-positive breast cancer.</p

A hydrofluoric acid-free method to dissolve and quantify silica nanoparticles in aqueous and solid matrices

As the commercial use of synthetic amorphous silica nanomaterials (SiO2-NPs) increases, their effects on the environment and human health have still not been explored in detail. An often-insurmountable obstacle for SiO2-NP fate and hazard research is the challenging analytics of solid particulate silica species, which involves toxic and corrosive hydrofluoric acid (HF). We therefore developed and validated a set of simple hydrofluoric acid-free sample preparation methods for the quantification of amorphous SiO2 micro- and nanoparticles. To circumvent HF, we dissolved the SiO2- NPs by base-catalyzed hydrolysis at room temperature or under microwave irradiation using potassium hydroxide, replacing the stabilizing fluoride ions with OH−, and exploiting the stability of the orthosilicic acid monomer under a strongly basic pH. Inductively coupled plasma – optical emission spectroscopy (ICP-OES) or a colorimetric assay served to quantify silicon. The lowest KOH: SiO2 molar ratio to effectively dissolve and quantify SiO2-NPs was 1.2 for colloidal Stöber SiO2-NPs at a pH >12. Fumed SiO2-NPs (Aerosil®) or food grade SiO2 (E551) containing SiO2-NPs were degradable at higher KOH: SiO2 ratios >8000. Thus, hydrofluoric acid-free SiO2- NP digestion protocols based on KOH present an effective (recoveries of <84%), less hazardous, and easy to implement alternative to current methods

Risk for pelvic metastasis and role of pelvic lymphadenectomy in node-positive vulvar cancer - results from the AGO-VOP.2 QS vulva study

Simple Summary In node-positive vulvar squamous cell cancer, questions of when and how to perform pelvic lymphadenectomy (LAE) as well as the optimal extent of pelvic treatment in general have been surrounded by considerable controversy. In Germany, systematic pelvic LAE is currently recommended as a staging procedure in patients at risk for pelvic nodal involvement in order to prevent morbidity caused by pelvic radiotherapy (RT) in patients without histologically-confirmed pelvic involvement. However, the population at risk for pelvic metastases remains insufficiently described, resulting in the potential overtreatment of a considerable proportion of patients with groin-positive disease. This applies to the indication to perform surgical staging but also to adjuvant RT of the pelvis without previous pelvic staging. Our study aims to describe the risk for pelvic lymph node metastasis with regard to positive groin nodes and to clarify the indication criteria for pelvic treatment in node-positive vulvar cancer. Abstract The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b

Uncertainties and controversies in axillary management of patients with breast cancer

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register