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Current public health initiatives to contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic focus on expanding vaccination efforts to include vulnerable populations such as pregnant people. Vaccines using messenger ribonucleic acid (mRNA) technology rely on translation by immune cells, primarily at the injection site. Hesitancy remains among the general population regarding the safety of mRNA vaccines during gestation, and it remains unknown whether the SARS-CoV-2 Spike protein (the product of mRNA vaccines available) accumulates in the placenta after vaccination. Objective: To determine whether Spike protein translation and accumulation occurs in placental tissue in the context of recent mRNA SARC-CoV-2 vaccination during pregnancy. We identified 48 patients receiving one or two doses of mRNA SARS-CoV-2 vaccine during gestation and used immunohistochemistry against SARS-CoV-2 Spike protein in formalin-fixed, paraffin-embedded placental tissue. One placenta, positive for SARS-CoV-2 RNA by in situ hybridization (ISH) was used as positive control. Seven term placentas collected prior to the emergence of SARS-CoV-2 served as negative controls. Eighty one percent of patients in the study group underwent third-trimester delivery; remaining had a first-trimester spontaneous abortion or elective second-trimester termination. Patients received two (52%) or one (48%) vaccine doses during pregnancy, with a median interval between latest dose and delivery of 13 days (range 2-79 days). Most (63%) cases had their latest dose within 15 days prior to delivery. All the placentas in the study and negative control groups were negative for SARS-CoV-2 immunohistochemistry. Six study cases with short vaccine-delivery intervals (2-7 days) were subjected to SARS-CoV-2 ISH and were negative. Our findings suggest that mRNA vaccines do not reach significant concentrations in the placenta given the absence of definitive SARS-CoV-2 Spike protein accumulation in placental tissue. This observation provides evidence supporting the safety of mRNA vaccines to the placental-fetal unit.

Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.

Objectives: To measure the diagnostic accuracy of intraoperative frozen section examination of sentinel lymph nodes (SLN) in vulvar cancer and to describe associated patient outcomes. Methods: This retrospective cohort study included patients with invasive squamous cell carcinoma of the vulva who underwent SLN biopsy with intraoperative frozen section at one cancer centre from Jan 2008 - Feb 2020. Exclusion criteria were tumor size >4cm, multifocal tumor, palpable groin lymph nodes and neoadjuvant therapy. The SLN procedure was performed by injection of the primary vulvar tumor or scar with technetium-99m, ICG and/or blue dye. We compared the intraoperative SLN frozen section diagnosis and the paraffin section report for concordance. Recurrence location was described and recurrence free survival (RFS) was compared using the Kaplan-Meier method. Results: A total of 173 patients (258 groins) met inclusion and exclusion criteria. On frozen section, there were 36/258 positive groins on frozen section and 222 negative groins. On final pathology, there were 39/258 positive groin nodes: 30 macro-metastases, 7 micro-metastases, 2 isolated tumor cells (ITCs). There were 219 negative groins. The sensitivity and specificity for frozen section detecting any metastatic disease compared to final pathology, was 89.7% and 99.5%, respectively. The positive-predictive value (PPV) was 97.2% and the negative-predictive-value (NPV) was 98.2%. There were 4 cases of false negative frozen section where final pathology revealed two cases of ITCs, 1 micro-metastasis and 1 macro-metastasis. A total of 30 patients (17.3%) underwent a full inguinal femoral lymphadenectomy during the same operation due to the frozen section results and avoided a second operation. A total of 2 patients (1.2%) required a second operation for lymphadenectomy due to false negative results on frozen section. Median (range) follow up was 38.0 (1-137.8) months. Median RFS was 14.9 (3.6 to 98.2) months. There were 46 recurrences in the study population, of which 29 were confined to the vulva, 9 groin recurrences and 8 distant recurrences. Among patients with a negative SLN biopsy on both frozen section and final pathology, there were 10 (3.9 %) groin and/or distant recurrences. A total of 6 nodal recurrences were ipsilateral, 1 was contralateral, 2 were bilateral and 1 recurrence was distant. After exclusion of patients with local recurrence only, the RFS at 3 years was 91.6% (95% CI 86.2-97.4%) for patients with negative SLN on frozen section and 64.6% (95% CI 46.5-89.7%) for positive SLN on frozen section. On final pathology, patients with negative SLN had a 3-year RFS of 91.7% (95% CI 86.3-97.4%), macro-metastases 58.4% (95% CI 38.5-87.7%), and micro-metastases/ITCs was 100%. Conclusions: Intraoperative frozen section of SLNs in vulvar cancer is an accurate intraoperative guide to determine if complete inguinal femoral lymphadenectomy should be performed. SLN biopsy reduced the need for a second surgical procedure and does not appear to compromise patient outcomes.

A risk-averse insurance company controls its reserve, modeled as a perturbed Cramer-Lundberg process, by choice of both the premium p and the deductible K offered to potential customers. The surplus is allocated to financial investment in a riskless and a basket of risky assets potentially correlating with the insurance risks and thus serving as a partial hedge against these. Assuming customers differ in riskiness, increasing p or K reduces the number of customers n ( p , K ) and increases the arrival rate of claims per customer λ ( p , K ) through adverse selection, with a combined negative effect on the aggregate arrival rate n ( p , K ) λ ( p , K ) . We derive the optimal premium rate, deductible, investment strategy, and dividend payout rate (consumption by the owner-manager) maximizing expected discounted lifetime utility of intermediate consumption under the assumption of constant absolute risk aversion. Closed-form solutions are provided under specific assumptions on the distributions of size and frequency of claims.

Introduction Substantial as opposed to focal or no lymphovascular space invasion (LVSI) is proposed as an independent adverse prognostic factor in patients with early-stage endometrioid endometrial cancer (EEC). We reviewed outcomes of patients treated with adjuvant vaginal brachytherapy (VB) alone in a single institution, stratified by LVSI extent. Methods and Materials Retrospective review identified Stage I-II EEC patients receiving VB alone from 2010 to 2017. Extent of LVSI was reported as none, focal, or substantial. Kaplan–Meier estimates and Log-Rank test were used to determine significance between variables. Cox proportional hazards model was used for multivariate analyses. Results In total, 325 patients were identified with a median follow-up of 35 (23–48) months. LVSI was found in 112 patients with extent reported in 78, 45 (58%) had focal, and 33 (42%) substantial LVSI. Estimated disease-free survival for those with substantial LVSI was 73 (57–94)%, focal LVSI 89 (79–100)%, and no LVSI 94 (90–98)% at 48 months (p = 0.012). On multivariate analyses substantial LVSI was the only risk factor predictive of pelvic [HR substantial vs no: 7.2 (1.0–51.6); p = 0.048] and distant failure [HR substantial vs no: 4.4 (1.2–16.3); p = 0.027]. Both high-grade disease [HR 3 vs 1: 5.5 (1.2–25.6); p = 0.031] and extent of LVSI [HR substantial vs no: 4.4 (1.7–11.4); p = 0.002] predicted for worse disease-free survival. Discussion Substantial LVSI was the strongest adverse prognostic factor for pelvic and distant failure in this cohort of EEC patients receiving adjuvant VB alone, suggesting this subset may benefit from additional adjuvant therapy. This study underscores the importance of quantifying LVSI extent in EEC.

Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words “verruciform” and “verrucous” were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.

Traditional approaches and debates in Agrifood Governance (AFG) have focused exclusively on the role of market forces and public policies. The emergence of alternative food movements, such as Territorial Short Food Supply Chains (TSFSCs), suggest the need to re-evaluate the role of civil society as a driver of governance mechanisms and a source of innovation and transformation of agrifood systems. This paper analyses the AFG processes that are configured in TSFSCs based on social discourses and coordination mechanisms of agents design. For this, the Q method and an exploratory/descriptive analysis are used, and the cities of Bogota (Colombia) and Cordoba (Spain) are taken as case studies. Results show five different social discourses around AFG: 1) food activism, 2) development cooperation, 3) market niche, 4) local self-management, and 5) social and ecological awareness. It is also noted that TSFSCs configure a mode of reflexive food governance. Coordination mechanisms of the SFSCs are mainly settled in the social and market sphere, and they are in line with features of governance network. These two governance approaches (reflexive and networked) operate in tandem, with important complementary and synergistic effects that foster food democracy.

Fish and other seafood products represent a valuable source of many nutrients and micronutrients for the human diet and contribute significantly to global food security. However, considerable amounts of seafood waste and by-products are generated along the seafood value and supply chain, from the sea to the consumer table, causing severe environmental damage and significant economic loss. Therefore, innovative solutions and alternative approaches are urgently needed to ensure a better management of seafood discards and mitigate their economic and environmental burdens. The use of emerging technologies, including the fourth industrial revolution (Industry 4.0) innovations (such as Artificial Intelligence, Big Data, smart sensors, and the Internet of Things, and other advanced technologies) to reduce and valorize seafood waste and by-products could be a promising strategy to enhance blue economy and food sustainability around the globe. This narrative review focuses on the issues and risks associated with the underutilization of waste and by-products resulting from fisheries and other seafood industries. Particularly, recent technological advances and digital tools being harnessed for the prevention and valorization of these natural invaluable resources are highlighted.

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductal-lobular system, and a non-obligate precursor of invasive disease. While there has been a significant increase in the diagnosis of DCIS in recent years due to uptake of mammography screening, there has been little change in the rate of invasive recurrence, indicating that a large proportion of patients diagnosed with DCIS will never develop invasive disease. The main issue for clinicians is how to reliably predict the prognosis of DCIS in order to individualize patient treatment, especially as treatment ranges from surveillance only, breast-conserving surgery only, to breast-conserving surgery plus radiotherapy and/or hormonal therapy, and mastectomy with or without radiotherapy. We conducted a semi-structured literature review to address the above issues relating to "pure" DCIS. Here we discuss the pathology of DCIS, risk factors for recurrence, biomarkers and molecular signatures, and disease management. Potential mechanisms of progression from DCIS to invasive cancer and problems faced by clinicians and pathologists in diagnosing and treating this disease are also discussed. Despite the tremendous research efforts to identify accurate risk stratification predictors of invasive recurrence and response to radiotherapy and endocrine therapy, to date there is no simple, well-validated marker or group of variables for risk estimation, particularly in the setting of adjuvant treatment after breast-conserving surgery. Thus, the standard of care to date remains breast-conserving surgery plus radiotherapy, with or without hormonal therapy. Emerging tools, such as pathologic or biologic markers, may soon change such practice. Our review also includes recent advances towards innovative treatment strategies, including targeted therapies, immune modulators, and vaccines.

The spectrum of mesenchymal neoplasia in the uterus has expanded in recent years. First, the identification of prevalent, recurrent molecular alterations has led to a more biologically and clinically congruent classification of endometrial stromal tumors. Likewise, the diagnostic criteria of several rare and miscellaneous tumor types have been refined in recent case series (Perivascular Epithelioid Cell tumor, inflammatory myofibroblastic tumor). Pure mesenchymal tumors are still broadly classified based on morphology according to the tumor cell phenotype. Smooth muscle tumors predominate in frequency, followed by tumors of endometrial stromal derivation; the latter are covered in depth in this article with an emphasis on defining molecular alterations and their morphologic and clinical correlates. The remaining entities comprise a miscellaneous group in which cell derivation does not have a normal counterpart in the uterus (eg, rhabdomyosarcoma) or is obscure (eg, undifferentiated uterine sarcoma). This article discusses their clinical relevance, recent insights into their molecular biology, and the most important differential diagnoses. Regarding the latter, immunohistochemistry and (increasingly) molecular diagnostics play a role in the diagnostic workup. We conclude with a few considerations on intraoperative consultation and macroscopic examination, as well as pathologic staging and grading of uterine sarcomas as per the most recent American Joint Cancer Commission and the Federation Internationale de Gynecologie et d'Obstetrique staging systems.

ObjectiveMucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical management of clinical stage I mucinous ovarian carcinoma by examining the prognostic significance of lymphadenectomy and intra-operative rupture on patient survival.MethodsWe conducted a retrospective cohort study of all pathology-reviewed invasive mucinous ovarian carcinomas diagnosed between 1999 and 2019 at two tertiary care cancer centers. Baseline demographics, surgical management details, and outcomes were collected. Five-year overall survival, recurrence-free survival, and the association of lymphadenectomy and intra-operative rupture on survival were examined.ResultsOf 170 women with mucinous ovarian carcinoma, 149 (88%) had clinical stage I disease. Forty-eight (32%; n=149) patients had a pelvic and/or para-aortic lymphadenectomy, but only 1 patient with grade 2 disease was upstaged due to positive pelvic lymph nodes. Intra-operative tumor rupture was documented in 52 cases (35%). On multivariable analysis, after adjusting for age, final stage, and use of adjuvant chemotherapy, there was no significant association between intra-operative rupture with overall survival (HR 2.2 (0.6–8.0); p=0.3) or recurrence-free survival (HR 1.3 (0.5–3.3); p=0.6), or lymphadenectomy with overall survival (HR 0.9 (0.3–2.8); p=0.9) or recurrence-free survival (HR 1.2 (0.5–3.0); p=0.7). Advanced stage was the only factor that was significantly associated with survival.ConclusionsIn clinical stage I mucinous ovarian carcinoma, systematic lymphadenectomy has low utility, as very few patients are upstaged and recurrence typically occurs in the peritoneum. Furthermore, intra-operative rupture does not appear to independently confer a worse survival, and therefore these women may not benefit from adjuvant treatment based on rupture alone.

Objectives: Mucinous ovarian carcinoma (MOC) is the most common histology in young women eligible for fertility-sparing surgery. The aim of the study was to evaluate the safety and reproductive outcomes after fertility-sparing surgery in invasive mucinous ovarian carcinomas. Methods: A retrospective review was performed of all MOCs diagnosed between 1999 and 2019 at two tertiary care cancer centers. Pathology was reviewed to rule out cases with metastasis from gastrointestinal tract primary. The demographics and survival outcomes were compared between women who underwent fertility-sparing surgery and those who underwent radical surgery (at least hysterectomy, bilateral salpingo-oophorectomy±staging). Five-year overall survival (OS) and recurrence free survival (RFS) were calculated from Kaplan-Meier curves and comparisons made using log-rank test. Cox proportional hazard models were constructed to evaluate the effect of fertility sparing surgery on survival. Results: Of 149 women with apparent stage I disease upon presentation, 43 (29%) underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy±omentectomy and lymphadenectomy. Compared to women who underwent radical surgery, these women were younger (30 years vs 55 years; p Conclusions: Fertility-sparing surgery in apparent stage I MOC is not associated with worse survival outcomes; however, it is important that candidates are carefully selected based on pathologic factors. In those with aggressive histologic components, radical surgery should be considered.

The 1995 CRA reform led to a two-tiered evaluation scheme determined by a bank's asset value. Using this feature, we estimate the cost of the CRA through the lens of costly actions taken by banks. Banks exploit the attribute-based regulation by strategically slowing asset growth, bunching below a $250M threshold. This regulatory avoidance also has real effects. Treated banks experience an increase in the rejection rate of LMI loans, while areas they serve experience a decline in the county-level share of small establishments and entrepreneurial innovation. Taken together, these results highlight a bank’s willingness to take costly actions to avoid increased regulatory oversight, and as a consequence, reduced credit access for individuals the CRA is designed to benefit.

In this paper we use the property that certainty equivalence, as implied by a first-order approximation to the solution of stochastic discrete-time models, breaks in its equivalent continuous-time version. We study the extent to which a first-order approximated solution built by perturbation methods accounts for risk. We show that risk matters economically in a real business cycle (RBC) model with habit formation, and capital adjustment costs and that neglecting risk leads to substantial pricing errors. A first-order approximation in continuous time reduces pricing errors by 90 percent relative to the certainty equivalent linear solution.

Urban food policies (UFPs) have emerged as a key mechanism to drive the transition towards more sustainable food systems, with cities as the appropriate scale for their implementation. The aim of the paper is analysis of the boost that UFPs have given to one of the most widespread forms of Alternative Food Networks, these are Territorial Short Food Supply Chains (TSFSCs). For this, the territorial factors that strengthen TSFSCs in the cities of Bogota (Colombia) and Cordoba (Spain), one being UFP, are prioritised using a multi-criteria model based on the Analytic Network Process. Based on this prioritisation, the way the UFPs interrelate with the other prioritised territorial factors in both cities is identified. Consequently, the influence of UFP implementation on social capital of TSFSCs is analysed through Social Network Analysis. The results indicate that there are four types of priority territorial sub-factors on which UFPs should have an impact in order to promote TSFSCs in the two cities. The first group is classified as means to achieve the other sub-factors. The other sub-factors are classified as ends. The main means are UFPs and partnership linkages. The territorial sub-factors included in the UFP are in the design and implementation phases of the policy cycle. Furthermore, UFPs foster bridging social capital, with actors connecting unconnected nodes. Finally, some of the reflections on the implications of UAPs indicate that the promotion of participatory governance mechanisms involving civil society is an important element to include in UFPs, given their influence on strengthening collective action and social capital in cities. This shows that a territorial approach in UFPs can have greater results in policy implementation. In this way the paper contributes, at the theoretical and empirical level, to recent debates on UFP approaches and the integration of key factors for food transformation in cities.

Mammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3-249 months). Positive final margin (tumor transected), age 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.

Neurological involvement in Behcet's disease is rare, especially at the onset. It can present in the form of parenchymal changes or as damage to the vascular structures in its nonparenchymal form. The coexistence of both kinds of manifestations in the same patient is exceptional. We report the case of a 32-year-old patient with a history of deep venous thrombosis, who was being treated for holocranial headache, apathy, and oral and genital ulcers. Brain magnetic resonance imaging showed hyperintense lesions in the basal ganglia and white matter, and the vascular study evidenced venous thrombosis of the left transverse sinus. After confirming the diagnosis of Behcet's disease with parenchymal and nonparenchymal cerebral involvement, immunosuppressive and corticosteroid therapy was started, resulting in the remission of the symptoms.

A subset of CD4+ T cells, known as T follicular helper (Tfh), provides co-stimulating signals required to establish long-term humoral immunity. Recent studies have shown a reduced frequency and functionality of this population in older adults in comparison to young adults, in response to vaccination. To evaluate whether memory generation of circulating Tfh (cTfh) cells contributes to this phenomenon, the memory subpopulations of cTfh, and their activation degree, were evaluated both ex-vivo and in-vitro, in response to the model antigen tetanus toxoid (TT) after the first dose of tetanus vaccine. Here, we report a lower frequency of cTfh after vaccination in older adults compared to young adults. Moreover, whereas cTfh from older adults preferably expanded with an effector memory phenotype, young adults experienced a temporal increase of CCR7+CD45RA+ cTfh cells, which also displayed higher levels of CD95, CD40L, CXCR3, and Bcl-6 upon antigen re-encounter. This phenotype was confirmed using automatized algorithm. In conclusion, our results suggest that an age-related loss of heterogeneity and an expansion of more differentiated memory cells within the cTfh compartment could affect the responsiveness of older individuals to vaccines, making this phenotype a characteristic feature of immunosenescence.

In this paper we use the property that certainty equivalence, as implied by a first-order approximation to the solution of stochastic discrete-time models, breaks in its equivalent continuous-time version. We derive a risk-sensitive first-order perturbation solution for a general class of rational expectations models. We show that risk matters economically in a real business cycle (RBC) model with habit formation and capital adjustment costs, and that neglecting risk leads to substantial pricing errors. A first-order perturbation provides a sensible approximation to the effects of risk in continuous-time models. It reduces pricing errors by around 90% relative to the certainty equivalent linear approximation.

This paper, based on a participatory methodological framework involving expert stakeholders and researchers from six European countries (Germany, Ireland, Poland, Spain, Sweden and UK), analyses the priority issues for the development of short-rotation plantations (SRP), and proposes a series of policy strategies to strengthen this development. The results indicate that there is a lack of awareness of the multifaceted benefits of SRP at the level of farmers, policy makers and public authorities. More research is required to put a value on the multifunctionality of SRP and justify its public support. Small-scale projects using established technologies are also required with energy crops introduced in a phased manner. The simultaneous dissemination of this knowledge upwards to policy makers and downwards to producers and farmers is critical in the success of SRP. Also, greater financial support on both the supply and demand side is highlighted as being necessary: on the supply side linking multifunctional benefits of SRP and targeted payments, along with increased long-term contractual arrangements between farmers and energy plant operators; demand side incentives should overcome any difference in price between fossil fuels and energy crops. Groups to lobby for the uptake and support of SRP and bioenergy are also of necessary.

Despite the growing importance of the digital transformation (DT) of the agrifood sector on the political agenda, traditional policies are not enough to provide proactive responses to rapid technological changes and new approaches for policy planning are necessary especially at regional level. This manuscript proposes and illustrates the implementation of a new methodological framework for DT policy planning in the case of Andalusia, the olive world leader region, but applicable to other regions and sectors, with two objectives: 1) to quantitatively determine the importance of the conditioning factors of DT in the olive sector in the short/medium term, by developing an AHP/SWOT/PESTLE model, and 2) to design public policies to strengthen the DT, taking advantage of the potentialities and alleviating the deficiencies, by carrying out a quantitative TOWS analysis. The knowledge of diverse groups of experts, i.e. stakeholders in the sector, has been used in all analyses due to the lack of reliable data and the complex nature of the issues analysed. The results show that the opportunities and strengths are more prominent than weaknesses and threats for DT. Environmental issues stand out as an opportunity to boost DT. There is also a growing interest in developing an interoperability strategy which is an opportunity to overcome the low technological integration of the value chain. DT can also enable a more transparent value chain and improved traceability. Some negative factors are the lack of evidence on the economic viability of investment in digital technologies, shortage of labour and young farmers, and potential unintended and unanticipated effects of DT. Important policies strategies to foster DT are: improving environmental efficiency though DT; promoting youth employment in the sector; enhancing coordination among innovation actors; developing a common interoperability strategy; and fostering technological integration in the sector.

Objectives: To determine the effect of lymphadenectomy and adjuvant chemotherapy on survival in stage I, grade 1 (G1) and 2 (G2) endometrioid ovarian cancer (EnOC) as there is limited evidence in this population. Methods: Retrospective cohort study of patients with stage I, G1 and G2 EnOC, treated at two cancer centers between 2001-2019. Demographic, surgical and follow up data was collected. Recurrence free survival (RFS) and overall survival (OS) were calculated from the Kaplan-Meier curves. Cox Proportional Hazard was used to evaluate predictive factors. Results: There were 192 G1 and G2 EnOC, 129 had stage I disease upon presentation. Twenty-nine patients were upstaged after surgery: 25 patients were stage II and 4 patients were stage III based on omental or bowel involvement. Nine patients had CT findings concerning for advanced stage, but were found to be stage I following surgery. In total, there were 131 patients with stage I disease. The median age for the stage I patients (n=131) was 54 (26-90) years, 80 patients had G1 and 51 had G2 disease, 84 patients were stage IA, 5 were IB and 42 were stage IC. Complete staging lymphadenectomy was performed in 34/131 (26.0%) whereas 97 had either partial (n=22) or no (n=75) surgical staging. Adjuvant chemotherapy was given in 30 patients. Median (95% CI) follow-up was 51.5 months (44.3-57.2). Median RFS was 48.2 (42.3-54.0) months and median OS time was 51.5 (44.3-57.2) months. In the univariate analysis, including age, complete staging, and chemotherapy, only grade was found to be significant with G2 more likely recurrence, compared to G1 patients (p=0.03). This was further validated in the multivariable analysis (p=0.04; HR=3.42 95% CI 1.03-11.38). There was no difference in RFS (p=0.57) and OS (p=0.30) in patients who underwent complete surgical staging compared to those that did not. None of the 56 patients that had complete (n=34) or partial (n=22) lymphadenectomy had positive lymph nodes. For a subgroup of 70 patients with stage IA/IB that did not have complete surgical staging, adjuvant chemotherapy was given to 10 patients. Sixty patients had no adjuvant treatment. Median (95% CI) follow-up was 58.0 (48.2-69.3) months. Median RFS was 56.7 (46.9-67.4) and median OS was 58.0 (48.2-69.3) months. There was no benefit in RFS (p=0.08) for stage IA/IB patients who received adjuvant chemotherapy (Figure 1). There was a trend toward no chemotherapy being superior to adjuvant chemotherapy in OS (p=0.05). Twelve patients had recurrence. One patient recurred in a lymph node and the peritoneum, 8 had a pelvic recurrence, 2 had peritoneal recurrence only, and 1 patient with fertility sparing surgery recurred in the remaining ovary. Three patients were salvageable at the time of recurrence and are alive with no disease. Conclusions: Patients with Stage I, G1 and G2 EnOC have excellent prognosis and staging lymphadenectomy does not improve RFS or OS. Morover, patients with stage IA/IB who did not have complete staging lymphadenectomy, did not benefit from adjuvant chemotherapy. Download : Download high-res image (70KB) Download : Download full-size image

Studies on the pattern-based classification for invasive endocervical adenocarcinoma showed that tumors with nondestructive invasion (pattern-A) have a 0% rate of nodal metastases. Our understanding of pattern-A tumors and their distinction from in-situ adenocarcinoma requires further study. Thirteen sections diagnosed independently as pattern-A adenocarcinoma by three gynecologic pathologists, and 14 sections of benign endocervix were selected. Three additional pathologists (reviewers) evaluated a digital image from each section and classified it as pattern-A or benign based on architecture only. To blind the interpretation to cytologic features, nuclei and cytoplasm were obscured using morphometric software (Zen 2011, Carl Zeiss Microscopy, Germany). 13/27 cases (48%; 8 pattern-A, 5 benign) were correctly classified by all reviewers; 19/27 (70%; 10 pattern-A, 9 benign) were correctly classified by ≥2 reviewers. 3/13 pattern-A cases (23%) were interpreted as benign by ≥2 reviewers. Conversely, 5/14 benign cervices (36%) were misinterpreted as pattern-A by ≥2 reviewers. The number of glands per 20× field was higher in pattern-A cases with high reviewer agreement (p=0.004). An abnormal architecture is seen in many pattern-A adenocarcinomas in support of their invasive nature; some, however, have architecture that overlaps with that of benign endocervix thus may actually represent in-situ lesions. Likewise, normal cervix can be architecturally complex and mirror patterns that pathologists would classify as pattern-A if malignant cytologic features were present. Based on this overlap and the nil risk of nodal spread, an emphasis on the non-destructive, rather than the invasive, nature of pattern-A adenocarcinoma is recommended.

• An integrated framework for policy design oriented to olive sustainability is proposed.

Using a novel data set of career histories in the film industry, we study the effect of housing wealth shocks on the quality of jobs that individuals pursue. Homeowners facing greater declines in local house price reduce their participation in high-quality projects, such as big-budget films and productions with award-winning talent, while increasing their involvement in low-quality films. Importantly, renters are not affected by these shocks. Consistent with individuals using home equity during job searches, these negative shocks have a greater impact on lower-equity and less-wealthy homeowners. Moreover, house price declines from the housing crisis also affect long-term career outcomes.

Olive cultivation for oil production in Tunisia covers from traditional to innovate cropping systems. The aim of the study was to assess the environmental footprint of the most representative olive growing systems of the actual production of olive fruit in Tunisia, from the planting phase to the full production phase, during a reference period of the life cycle of the olive growth of 50 years. Six traditional systems, two intensive systems and one super-intensive system were compared and the differences of type of production (conventional or organic), irrigation management and fertilization management were selected. The impacts associated to olive production were calculated and evaluated by the Life Cycle Assessment methodology and the results of this study were referred to two functional units: 1 ton of olives and 1 ha of cultivated olive growing area. Field agricultural practices of olive systems were soil management, fertilizers, pesticides, pruning and harvesting. The impact categories selected for the environmental analysis were climate change, acidification, freshwater eutrophication and freshwater ecotoxicity. The most innovative olive production systems (intensive and super-intensive) resulted in less environmental impacts for all categories with respect to the rest of systems from the productive perspective but produced higher impacts per hectare of cultivated area. Fertilizers and soil management were the field agricultural practices that presented the highest contributions in most of the categories evaluated. The implementation of an integrated crop management, as well as good practice guides and training programs for farmers, should be considered a priority.

Endometrial ablation is commonly performed to manage heavy menstrual bleeding. However, failure in symptom control eventually requiring hysterectomy is frequent. Adenomyosis is common in such failure cases. Ablations using a resectoscope will produce an Endo-Myometrial Resection (EMR) specimen. The value of histopathologic examination of EMRs in predicting treatment failure and adenomyosis has not been addressed. We retrieved histologic material from subjects with failed ablation (persistent symptoms requiring hysterectomy) and subjects with ablation followed by clinical improvement and no hysterectomy (control group). Material was evaluated for features of an abnormal endometrial distribution suggestive of adenomyosis: myometrial fragments with endometrium on opposite edges, myometrium with endometrium in ≥3 edges and areas of endometrium completely surrounded by myometrium (endometrial islands). Hysterectomy specimens from the study group were evaluated for the presence of adenomyosis and its distribution (superficial/deep). Both study and control groups consisted of 18 patients each. The number of fragments with endometrium on opposite sides was significantly higher in the study group: 2.11 vs 0.94 in the control group (p=0.005). Conversely, maximum aggregate dimension (2.3cm vs 2.79cm), number of fragments with endometrium on three sides (4.5 vs 2.78) and number of fragments with endometrial islands (4.5 vs 4.11) did not significantly differ between groups. Adenomyosis was seen in 72.2% hysterectomies from the study group; 27.8% involved deep myometrium. None of the EMR features were statistically associated with adenomyosis. Certain endomyometrial distribution patterns in EMR specimens correlate with future ablation failure and need for definitive surgery. This may be explained by residual endometrial tissue not resected due to a markedly irregular endomyometrial interface. Adenomyosis is frequent in cases of ablation failure. However, a significant association between EMR patterns studied and adenomyosis was not observed.

A pattern-based classification for invasive endocervical adenocarcinoma has been proposed as predictive of the risk of nodal metastases. We aimed to determine the reproducibility of such classification in the context of common diagnostic challenges: distinction between in situ and invasive adenocarcinoma and depth of invasion measurement. Nine gynecologic pathologists independently reviewed 96 cases of endocervical adenocarcinoma (two slides per case). They diagnosed each case as in situ or invasive carcinoma classifying the latter following the pattern-based classification as pattern A (non-destructive), B (focally destructive) or C (diffusely destructive). Depth of invasion, when applicable, was measured (mm). Overall, diagnostic reproducibility of pattern diagnosis was good (κ=0.65). Perfect agreement (9/9 reviewers) was seen in only 11 cases (11%), all destructively invasive (10 pattern C and 1 pattern B). In all, ≥5/9 reviewer concordance was achieved in 82/96 cases (85%). Distinction between in situ and invasive carcinoma, regardless of the pattern, showed only slight agreement (κ=0.37). Likewise, distinction restricted to in situ versus pattern A was poor (κ=0.23). Distinction between non-destructive (in situ+pattern A) and destructive (patterns B+C) carcinoma showed significantly higher agreement (κ=0.62). Estimation of depth of invasion showed excellent reproducibility (ICC=0.82). However, different measurements resulting in differing FIGO stages were common (from at least 1 reviewer in 79% cases). On the basis of interobserver agreement, the pattern-based classification is best at diagnosing destructive invasion, which carries a risk for nodal metastases. Agreement in diagnosing in situ versus invasive carcinoma, including pattern A, was poor. Given the nil risk of nodal spread in in situ and pattern A lesions, the term 'endocervical adenocarcinoma with non-destructive growth' can be considered when the distinction is difficult, after excluding destructive invasion. Depth of invasion measurement was highly reproducible among pathologists; thus, the pattern-based approach can complement, but should not replace, the depth of invasion metric.

The spread of biofuels has generated controversy at international, national and regional levels due to the environmental, economic and social impacts that its production and consumption can cause. Recently, the Spanish government has been promoting the production of biodiesel in industrial plants located in Spain and other EU countries. These developments are expected to stimulate the cultivation of rapeseed in the EU to the detriment of extra-EU imports of biodiesel mainly based on soybean oil from Argentina, which has been one of the main suppliers of biodiesel in Spain for years. As a result, the environmental impacts produced throughout the life cycle of biodiesel consumed in Spain could be radically affected. In this context, the environmental impacts of biodiesel produced in Spain and Argentina with rapeseed cultivated in Spain and soybean cultivated in Argentina were compared under certain growing conditions using life cycle assessment (LCA). Consequential and attributional approaches were compared under the ReCiPe method to test potential biases. The results showed that the biodiesel produced with Argentinean soybean oil had fewer environmental impacts than biodiesel produced with Spanish rapeseed oil. Seed production (and fertilization) was the process (and sub-process) that generated the greatest environmental burdens, and it is an area in which improvement is necessary in order to increase sustainability, particularly with regard to Spanish rapeseed-based biodiesel.

To reconstruct the paleoenvironments of the Cansona Formation, a Cretaceous succession in Colombia that has controversial paleoenvironmental interpretation, occasionally deep marine and occasionally shallow marine, palynofacies analyses were conducted on 93 samples from four sections of the Sinu San Jacinto Basin in the north, midwest, and southwest sectors. For the palynofacies analyses, the kerogen categories were counted and subjected to cluster analyses. Four palynofacies associations were revealed for the four sections: Palynofacies Association I (PA I), which consisted of microforaminiferal linings, scolecodonts, dinoflagellate cysts, pollen grains, and fungi hyphae; PA II, which consisted of phytoclast translucent non-biostructured and biostructured, opaque phytoclasts (equidimensional and lath shaped); PA III, which consisted of pseudoamorphous particles, cuticles, resin, and fungal spores; and PA IV, which consisted of fluorescent and non-fluorescent amorphous organic matter and the fresh-water algae Botryococcus . In contrast to early studies that suggested a generalization of the depositional environment for the Cansona Formation (deep or shallow conditions), this study suggests that the formation reflects conspicuous stratigraphic and lateral changes and hence different depositional environments. The Cerro Cansona (CC4 section) and Chalan (AP section) areas are a more marine proximal settings (Early Campanian-Maastrichtian), and there is an intermediate setting for the Lorica area (SC section) and deeper conditions for the Monteria area (CP2 section).

Hemangiomas of the uterine cervix are rare with only about 55 cases reported in the literature. Increased awareness of this unusual cervical lesion can lead to early diagnosis and conservative therapeutic approaches. We present a series of four patients with cervical hemangioma with an extensive review of the existing literature on the subject. All four cervical hemangiomas were diagnosed incidentally in hysterectomy specimens performed for persistent menorrhagia or pain. The mean age at presentation was 34 years. The mean lesion size was 2.1cm and the dominant location was posterior cervix (3 cases). Immunohistochemistry for estrogen and progesterone receptors showed expression of both markers in endothelial cells and stroma, the latter marker showing a stronger and more diffuse pattern. No other significant uterine abnormality was identified in two cases. The vast majority of cervical hemangiomas reported are in reproductive age women. In addition, these lesions express hormone receptors, indicating that their growth is at least in part due to sex hormone stimulation. Although most lesions are symptomatic (mostly bleeding), the diagnosis is frequently unsuspected. Cervical hemangiomas are benign with no recurrences or adverse outcomes reported to date. Conservative treatments are usually successful, and spontaneous remission has been observed. This entity should be included in the differential diagnosis of patients with abnormal vaginal bleeding, particularly in patients of reproductive age with no other clinical and radiologic findings that would explain the symptoms.

This article examines 1) the factors that condition the implementation of Quality Management Systems (QMS) meeting the requirements of ISO 9001 in the olive oil industry of Andalusia, the world-leading olive oil producing region in southern Spain; and 2) whether the implementation of ISO 9001 is associated with the use of better manufacturing and marketing practices by these industries. The study is based on a survey of 101 olive oil enterprises. As conditioning factors, the managerial and supervisory staff of ISO 9001 enterprises tend to be younger and more dynamic, highly educated and more in touch with new, high-quality sources of information, more willing to take risks, less focused on economic profit, and more oriented to selling olive oil further and faster. Good manufacturing practices are, in general, widespread in the Andalusian olive oil industry. Regarding marketing practices, ISO 9001 industries are more reliant on the use of ICTs and on the diversification of the type of olive oil sold. The policy implications of the work carried out are diverse if a wider implementation of ISO 9001 and better practices are the aim: fostering rejuvenation and formal education; training and information programmes based on successful ISO 9001 enterprises; proving the economic viability of ISO 9001; improving access to credit; and developing innovative marketing strategies.

Objective The post-reconstitution chemical stability and microbial challenge hold time of nonpreserved telavancin for injection was determined using common reconstitution diluents and intravenous (IV) infusion solutions stored at room temperature with light (ambient) or at 2°C to 8°C without light (refrigeration). Methods Telavancin was reconstituted with 5% dextrose, 0.9% normal saline, or sterile water (15 mg/mL). Infusion solutions at 0.6 and 8.0 mg/mL were prepared in ViaFlex (polyvinyl chloride) IV bags (Baxter International Inc, Deerfield, Illinois) using 5% dextrose, 0.9% normal saline, or lactated Ringer's solution. Chemical stability was evaluated for up to 14 days under refrigeration and for up to 3 days under ambient conditions. Telavancin concentration and degradant levels were determined using a stability-indicating HPLC method. Solutions were subjected to microbial-challenge testing for up to 48 hours (ambient) or for up to 6 days (refrigeration). Results All reconstituted or infused telavancin solutions met the prespecified stability acceptance criteria after 2 days under ambient and minimum 7 days under refrigeration. Following inoculation with gram-positive and gram-negative microorganisms, telavancin infusion solutions stored under ambient conditions reduced or inhibited populations of all organisms up to 48 hours, except for Serratia marcescens , which exhibited growth of >0.5 log 10 after 12 hours. All refrigerated samples inhibited or reduced bacterial populations up to 6 days. Conclusions These results are supportive of a total hold time for reconstituted telavancin in vials plus the time in IV infusion solutions in polyvinyl chloride bags to not exceed 12 hours under ambient conditions and 7 days under refrigeration.