Diagnosis for ecological intensification of maize-based smallholder farming systems in the Costa Chica, Mexico

Enhanced utilization of ecological processes for food and feed production as part of the notion of ecological intensification starts from location-specific knowledge of production constraints. A diagnostic systems approach which combined social-economic and production ecological methods at farm and field level was developed and applied to diagnose extent and causes of the perceived low productivity of maize-based smallholder systems in two communities of the Costa Chica in South West Mexico. Social-economic and production ecological surveys were applied and complemented with model-based calculations. The results demonstrated that current nutrient management of crops has promoted nutrition imbalances, resulting in K- and, less surprisingly N-limited production conditions, reflected in low yields of the major crops maize and roselle and low resource use efficiencies. Production on moderate to steep slopes was estimated to result in considerable losses of soil and organic matter. Poor crop production, lack of specific animal fodder production systems and strong dependence on animal grazing within communal areas limited recycling of nutrients through manure. In combination with low prices for the roselle cash crop, farmers are caught in a vicious cycle of cash shortage and resource decline. The production ecological findings complemented farmers opinions by providing more insight in background and extent of livelihood constraints. Changing fertilizer subsidies and rethinking animal fodder production as well as use of communal lands requires targeting both formal and informal governance structures. The methodology has broader applicability in smallholder systems in view of its low demand on capital intensive resource

Аналіз тенденцій рівня розвитку економічних процесів підприємства

Подано методичні розробки щодо визначення ймовірної зміни рівнів розвитку економічних процесів машинобудівних підприємств залежно від рівня ефективності матеріальної мотивації персоналу на період 2010 р. Імовірну зміну рівня розвитку економічного процесу визначено за допомогою ланцюгів Маркова, що передбачає реалізацію шести послідовних етапів. Ключові слова: підприємства машинобудування, ланцюги Маркова, економічні процеси.Представлены методические разработки по определению вероятного изменения уровня развития экономических процессов предприятий машиностроения в зависимости от уровня эффективности материальной мотивации персонала на период 2010 г. Вероятное изменение уровня развития экономического процесса определено с помощью цепей Маркова, что предусматривает реализацию шести последовательных этапов. Ключевые слова: предприятия машино-стро¬ения, цепи Маркова, экономические процессы.The paper presents methodical developments on determination of probable changes in the level of machine-build enterprises’ economic processes development depending on the level of personnel’s material motivation efficiency for the period of 2010. Probable changes in the level of economic processes development are determined by using Markov’s chains which provide six stages. Keywords: machine-building enterprises, Markov chains, economic processes

Predicting Long-term Disease-free Survival after Resection of Pancreatic Ductal Adenocarcinoma:A Nationwide Cohort Study

Objective: To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after the resection of pancreatic ductal adenocarcinoma (PDAC). Background: Despite high recurrence rates, 10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making. Methods: This nationwide cohort study included all consecutive patients who underwent PDAC resection in the Netherlands (2014-2016). The best-performing prognostic model was selected by Cox-proportional hazard analysis and Akaike's Information Criterion, presented by hazard ratios (HRs) with 95% confidence intervals (CIs). Internal validation was performed, and discrimination and calibration indices were assessed. Results: In all, 836 patients with a median follow-up of 67 months (interquartile range 51-79) were analyzed. Long-term DFS was seen in 118 patients (14%). Factors predictive of long-term DFS were low preoperative carbohydrate antigen 19-9 (logarithmic; HR 1.21; 95% CI 1.10-1.32), no vascular resection (HR 1.33; 95% CI 1.12-1.58), T1 or T2 tumor stage (HR 1.52; 95% CI 1.14-2.04, and HR 1.17; 95% CI 0.98-1.39, respectively), well/moderate tumor differentiation (HR 1.44; 95% CI 1.22-1.68), absence of perineural and lymphovascular invasion (HR 1.42; 95% CI 1.11-1.81 and HR 1.14; 95% CI 0.96-1.36, respectively), N0 or N1 nodal status (HR 1.92; 95% CI 1.54-2.40, and HR 1.33; 95% CI 1.11-1.60, respectively), R0 resection margin status (HR 1.25; 95% CI 1.07-1.46), no major complications (HR 1.14; 95% CI 0.97-1.35) and adjuvant chemotherapy (HR 1.74; 95% CI 1.47-2.06). Moderate performance (concordance index 0.68) with adequate calibration (slope 0.99) was achieved. Conclusions: The developed prediction model, readily available at www.pancreascalculator.com, can be used to estimate the probability of long-term DFS after resection of pancreatic ductal adenocarcinoma.</p

Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance

In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaff

Cholangiocarcinoma 2020: the next horizon in mechanisms and management

| Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted

Nationwide practice and outcomes of endoscopic biliary drainage in resectable pancreatic head and periampullary cancer

Background: Guidelines advise self-expanding metal stents (SEMS) over plastic stents in preoperative endoscopic biliary drainage (EBD) for malignant extrahepatic biliary obstruction. This study aims to assess nationwide practice and outcomes. Methods: Patients with pancreatic head and periampullary cancer who underwent EBD before pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2017–2018). Multivariable logistic and linear regression models were performed. Results: In total, 575/1056 patients (62.0%) underwent preoperative EBD: 246 SEMS (42.8%) and 329 plastic stents (57.2%). EBD-related complications were comparable between the groups (44/246 (17.9%) vs. 64/329 (19.5%), p = 0.607), including pancreatitis (22/246 (8.9%) vs. 25/329 (7.6%), p = 0.387). EBD-related cholangitis was reduced after SEMS placement (10/246 (4.1%) vs. 32/329 (9.7%), p = 0.043), which was confirmed in multivariable analysis (OR 0.36 95%CI 0.15–0.87, p = 0.023). Major postoperative complications did not differ (58/246 (23.6%) vs. 90/329 (27.4%), p = 0.316), whereas postoperative pancreatic fistula (24/246 (9.8%) vs. 61/329 (18.5%), p = 0.004; OR 0.50 95%CI 0.27–0.94, p = 0.031) and hospital stay (14.0 days vs. 17.4 days, p = 0.005; B 2.86 95%CI −5.16 to −0.57, p = 0.014) were less after SEMS placement. Conclusion: This study found that preoperative EBD frequently involved plastic stents. SEMS seemed associated with lower risks of cholangitis and less postoperative pancreatic fistula, but without an increased pancreatitis risk

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial

Background Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4–12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and

E2F7 represses a network of oscillating cell cycle genes to control S-phase progression

E2F transcription factors are known to be important for timely activation of G(1)/S and G(2)/M genes required for cell cycle progression, but transcriptional mechanisms for deactivation of cell cycle-regulated genes are unknown. Here, we show that E2F7 is highly expressed during mid to late S-phase, occupies promoters of G(1)/S-regulated genes and represses their transcription. ChIP-seq analysis revealed that E2F7 binds preferentially to genomic sites containing the TTCCCGCC motif, which closely resembles the E2F consensus site. We identified 89 target genes that carry E2F7 binding sites close to the transcriptional start site and that are directly repressed by short-term induction of E2F7. Most of these target genes are known to be activated by E2Fs and are involved in DNA replication, metabolism and DNA repair. Importantly, induction of E2F7 during G(0)-G(1)/S resulted in S-phase arrest and DNA damage, whereas expression of E2F7 during G(2)/M failed to disturb cell cycle progression. These findings provide strong evidence that E2F7 directly controls the downswing of oscillating G(1)/S genes during S-phase progression

Changes in mRNA expression profile underlie phenotypic adaptations in creatine kinase-deficient muscles.

We have studied the mechanisms that regulate the remodeling of the glycolytic, mitochondrial and structural network of muscles of creatine kinase M (M-CK)/sarcomeric mitochondrial creatine kinase (ScCKmit) knockout mice by comparison of wild-type and mutant mRNA profiles on cDNA arrays. The magnitudes of changes in mRNA levels were most prominent in M-CK/ScCKmit (CK(-/-)) double mutants but did never exceed those of previously observed changes in protein level for any protein examined. In gastrocnemius of CK(-/-) mice we measured a 2.5-fold increase in mRNA level for mitochondrial encoded cytochrome c oxidase (COX)-III which corresponds to the increase in protein content. The level of the nuclear encoded mRNAs for COX-IV, H(+)-ATP synthase-C, adenine nucleotide translocator-1 and insulin-regulatable glucose transporter-4 showed a 1.5-fold increase, also in agreement with protein data. In contrast, no concomitant up-regulation in mRNA and protein content was detected for the mitochondrial inorganic phosphate-carrier, voltage-dependent anion channel and certain glycolytic enzymes. Our results reveal that regulation of transcript level plays an important role, but it is not the only principle involved in the remodeling of mitochondrial and cytosolic design of CK(-/-) muscles