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Wave-transported boulders represent important records of storm and tsunami impact over geological timescales. Their use for hazard assessment requires chronological information on their displacement that in many cases cannot be achieved by established dating approaches. To fill this gap, this study investigated, for the first time, the potential of optically stimulated luminescence rock surface exposure dating (OSL-RSED) for estimating cliff-detachment ages of wave-transported coastal boulders. The approach was tested on calcarenite clasts at the Rabat coast, Morocco. Calibration of the OSL-RSED model was based on samples with rock surfaces exposed to sunlight for ∼ 2 years, and OSL exposure ages were evaluated against age control deduced from satellite images. Our results show that the dating precision is limited for all targeted boulders due to the local source rock lithology which has low amounts of quartz and feldspar. The dating accuracy may be affected by erosion rates on boulder surfaces of 0.02–0.18 mm yr−1. Nevertheless, we propose a robust relative chronology for boulders that are not affected by significant post-depositional erosion and that share surface angles of inclination with the calibration samples. The relative chronology indicates that (i) most boulders were detached from the cliff by storm waves; (ii) these storms lifted boulders with masses of up to ∼ 24 t; and (iii) the role of storms in the formation of boulder deposits along the Rabat coast is more significant than previously assumed. Although OSL-RSED cannot provide reliable absolute exposure ages for the coastal boulders in this study, the approach has large potential for boulder deposits composed of rocks with larger amounts of quartz or feldspar and less susceptibility to erosion.

Severe flooding was prevalent within the authors' region at the beginning of the school year. Many homes and fields were affected by the amount of rain that fell within a short period of time over multiple days. Their students were concerned about the impact this natural phenomena was having on their local community. Natural phenomena can provide wonderful learning opportunities for students to identify solutions to problems using engineering practices (Achieve 2016). Engineering is a pivotal discipline within the Next Generation Science Standards (NGSS Lead States 2013) because children can apply their knowledge of science concepts to solve real-life problems (NRC 2012). Therefore, the authors utilized this natural phenomena the students were experiencing to set the stage for an integrated science and engineering unit. Students in an afterschool program were given the problem that the local basketball team needed extra energy so they needed the students help with growing plants. However since the area was getting too much water, the plants were dying. What could the students do to help with this problem? The students worked on a solution for one hour a week over a six-week period. After reflecting on the unit, the authors believe it would have been better to implement the lessons in the spring. During the spring, garden plants are available and investigations could occur outdoors for a more authentic learning experience. In addition, they recommend providing more opportunities for students to observe their plants throughout the week so that they can document daily rather than weekly changes. However, regardless of these changes, they found the unit helped the students learn about the needs of plants and allowed them to apply this knowledge when designing a water diversion structure.

Mapping the spatial and temporal dynamics of species distributions is necessary for biodiversity conservation land-use planning decisions. Recent advances in remote sensing and machine learning have allowed for high-resolution species distribution modeling that can inform landscape-level decision-making. Here we compare the performance of three popular Sentinel-2 (10-m) land cover maps, including dynamic world (DW), European land cover (ELC10), and world cover (WC), in predicting wild bee species richness over southern Norway. The proportion of grassland habitat within 250 m (derived from the land cover maps), along with temperature and distance to sandy soils, were used as predictors in both Bayesian regularized neural network and random forest models. Models using grassland habitat from DW performed best (RMSE = 2.8 ± 0.03; average ± standard deviation across models), followed by ELC10 (RMSE = 2.85 ± 0.03) and WC (RMSE = 2.87 ± 0.02). All satellite-derived maps outperformed a manually mapped Norwegian land cover dataset called AR5 (RMSE = 3.02 ± 0.02). When validating the model predictions of bee species richness against citizen science data on solitary bee occurrences using generalized linear models, we found that ELC10 performed best (AIC = 2278 ± 4), followed by WC (AIC = 2367 ± 3), and DW (AIC = 2376 ± 3). While the differences in RMSE we observed between models were small, they may be significant when such models are used to prioritize grassland patches within a landscape for conservation subsidies or management policies. Partial dependencies in our models showed that increasing the proportion of grassland habitat is positively associated with wild bee species richness, thereby justifying bee conservation schemes that aim to enhance semi-natural grassland habitat. Our results confirm the utility of satellite-derived land cover maps in supporting high-resolution species distribution modeling and suggest there is scope to monitor changes in species distributions over time given the dense time series provided by products such as DW.

High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is an option to consolidate remission in Waldenstrom’s macroglobulinemia (WM), particularly in selected younger patients with chemosensitive disease. BEAM, consisting of BCNU, etoposide, cytarabine, and melphalan, is often used as a conditioning regimen. However, problems with BCNU, including pneumotoxicity, tolerance, and availability, necessitate the search for alternatives. In this pilot study, we investigated high-dose chemotherapy with BeEAM, in which BCNU is replaced with high-dose bendamustine as an alternative conditioning regimen in six subsequent patients with WM. Bendamustine treatment was well tolerated without unexpected toxicities. The overall response rate was 6/6 patients (2 very good partial responses (VGPR) and 4 PR). After a median follow-up of 72 months, two (33%) patients relapsed. Median progression-free and overall survivals were not reached, and no severe late-onset toxicities were observed so far. In this pilot study, BeEAM conditioning before ASCT seems feasible, safe, and effective in patients with WM.

Wetlands are important habitats for biodiversity and provide ecosystem services such as climate mitigation and carbon storage. The current wetland mapping techniques in Norway are tedious and costly, and remote sensing provides an opportunity for large-scale mapping and ecosystem accounting. We aimed to implement a deep learning approach to mapping wetlands with Sentinel-2 and LiDAR data over southern Norway. Our U-Net model, implemented through Google Earth Engine and TensorFlow, produced a wetland map with a balanced accuracy rate of 90.9% when validated against an independent ground-truth sample. This represents an improvement upon manually digitized land cover maps in Norway, which achieved accuracy rates of 46.8% (1:50,000 map) and 42.4% (1:5000 map). Using our map, we estimated a total wetland coverage area of 12.7% in southern Norway, which is double the previous benchmark estimates (5.6%). We followed an iterative model training and evaluation approach, which revealed that increasing the quantity and coverage of labeled wetlands greatly increases the model performance. We highlight the potential of satellite-based wetland maps for the ecosystem accounting of changes in wetland extents over time—something that is not feasible with traditional mapping methods.

Our broad aim was to systematically analyse research on the effect of COVID-19 on smallholder farming during 2019–2021 and to discuss how the research could be beneficial to smallholder farm resilience to future pandemics. The review methods were based on PRISMA guidelines, and 53 articles were included in the final review. The review aims to document the social-economic impacts on different groups, barriers and opportunities of smallholder farmers adapting to COVID, and policy options. Barriers to adaptations were considered in only 15% of journal articles, suggesting a research gap. This review highlights the fact that, among others, technology access to ensure information and crisis communication that specifically targets smallholders, as well as multi-layered diversification, serves as good predictors of smallholder adaptation to COVID-19. Multi-layered diversification includes product diversification, market diversification and income stream diversification. This confirms the established knowledge in disasters and livelihood studies where diversification of livelihoods portfolio serves as the key factor to resilience against shocks and crisis. Finally, we summarised the different policy implications arising from the literature. This implies that governments must develop an effective policy-mix that leaves no smallholder farmers behind in future pandemics.

By focusing on the personalization principle, the present study investigates whether two different language presentation formats of a multimedia presentation influence students' learning outcome and how individual interest towards the learning material moderates this impact. German students (N = 104) were randomly assigned to either a conversational or a formal language format of the multimedia presentation that taught Gestalt Laws. The results of this study showed that there were more positive effects on the learning performance in the conversational presentation format than the formal language format. This was, therefore, an indication of the effects of personalization. Furthermore, individual interest is a significant predictor for learning in this study. By testing different percentiles of individual interest, the findings showed that students with intermediate interest were affected by the format of language style. In contrast, learning results of students with the very lowest and very highest individual interest were not affected by different language styles. These results underline the necessity to take into account individual motivational prerequisites when designing multimedia learning environments.

• Mg-rich nm-scale precipitates exist in the C36 and the C14 laves phases. • The electrochemical activity (C15>C36>α-SS>C14) accounts in the passive state. • Interconnected C14 laves phases increases the corrosion current density. • Small and dispersed C15 laves phases decrease the corrosion current density. • Interconnected C36 laves phases cause minimal corrosion current densities. The electrochemical corrosion mechanisms of Mg alloys were extensively studied in previous investigations of different chemical compositions, modified surface states and various electrolyte conditions. However, recent research focused on the active state of Mg dissolution, leading to unresolved effects of secondary phases adjacent to a stable α-solid solution passive layer. The present study investigates the fundamental electrochemical corrosion mechanisms of three different Laves phases with varying phase morphologies and phase fractions in the passive state of Mg-Al-Ca alloys. The microstructure was characterized by (transmission-) electron microscopy and synchrotron-based transmission X-ray microscopy. The electrochemical corrosion resistance was determined with a standard three-electrode setup and advanced in-situ flow cell measurements. A new electrochemical activity sequence (C15>C36>α-Mg>C14) was obtained, as a result of a stable passive layer formation on the α-solid solution. Furthermore, nm-scale Mg-rich precipitates were identified within the Laves phases, which tend to inhibit the corrosion kinetics. [Display omitted] [ABSTRACT FROM AUTHOR]

Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage. Since sperm DNA damage may reduce embryo quality and increase miscarriage rates, it is possible that untreated sperm oxidative stress may impair in vitro fertilization (IVF) live birth rates. Given that the antioxidant Menevit is reported to reduce sperm DNA damage, it was hypothesized that men's consumption of this supplement may alter IVF outcomes. Therefore, a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer. Men were classified as controls if they were taking no supplements, health conscious controls if taking “general health” supplements, or Menevit users. Men with karyotype abnormalities, or cycles using donated, frozen and surgically extracted sperm were excluded. Among the final study cohort of 657 men, live birth rates were significantly higher in Menevit users than controls (multivariate adjusted odds ratio [OR]: 1.57, 95% confidence interval [CI]: 1.01–2.45, P= 0.046), but not between controls taking no supplements and those using general health supplements, thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users. Interestingly, in a post hoc sensitivity analysis, live birth rates among Menevit users were statistically superior to controls for lean men (OR: 2.73, 95% CI: 1.18–6.28; P= 0.019), not their overweight/obese counterparts (OR: 1.29, 95% CI: 0.75–2.22, P = 0.37). The results of this large cohort study therefore support a positive association between men's use of the Menevit antioxidant during IVF treatment and live birth rates, especially in lean individuals.

Die Technik des genetischen Erhaltungsgebiets ist ein anwendungsbereites Verfahren zur In-situ-Erhaltung von wildlebenden Verwandten unserer Kulturpflanzen. Bei dem Verfahren wird die dynamische Erhaltung von Populationen, die in ihren natürlichen Lebensräumen Evolutionsprozessen ausgesetzt sind, mit der statischen Erhaltung pflanzengenetischer Ressourcen in Genbanken kombiniert und somit die nachhaltige Nutzung dieser Arten ermöglicht. Im Modell- und Demonstrationsvorhaben "Genetische Erhaltungsgebiete für Wildselleriearten (Apium und Helosciadium) als Bestandteil eines Netzwerks genetischer Erhaltungsgebiete in Deutschland" (GESell) wurden wissenschaftliche und organisatorische Fragestellungen zur Umsetzung dieser Technik bearbeitet. Ziel des Projekts war die modellhafte Einrichtung von 45 genetischen Erhaltungsgebieten (GenEG) für Wildselleriearten und der Aufbau eines bundesweiten Netzwerks aus lokalen Akteuren. Zur Identifizierung der GenEG wurde das monografische Verfahren angewendet. Für die vier in Deutschland vorkommenden Wildselleriearten wurden zum Projektstart im Jahr 2015 aus 2400 Fundortdaten 322 Standorte für Präsenzkontrollen ausgewählt. Im Anschluss wurden für rund 100 möglichst vitale und ungefährdete Vorkommen, die sich über verschiedene Naturräume und Habitate verteilen, genetische Diversitätsanalysen durchgeführt. Anhand der Kartierungs- und Analyseergebnisse wählte das Projektteam zwischen 11 und 15 Vorkommen pro Art aus, die insgesamt die innerartliche Vielfalt der jeweiligen Arten bestmöglich repräsentieren. Für diese Vorkommen wurden die Einrichtung und ein langfristiges Management der GenEG in Zusammenarbeit mit lokalen Akteuren angestrebt. Bis zum April 2020 wurden bereits 15 GenEG eingerichtet.

An automated recognition of faces enables machines to visually identify a person and to gain access to non-verbal communication, including mimicry. Different approaches in lab settings or controlled realistic environments provided evidence that automated face detection and recognition can work in principle, although applications in complex real-world scenarios pose a different kind of problem that could not be solved yet. Specifically, in autonomous driving—it would be beneficial if the car could identify non-verbal communication of pedestrians or other drivers, as it is a common way of communication in daily traffic. Automated identification from observation whether pedestrians or other drivers communicate through subtle cues in mimicry is an unsolved problem so far, as intent and other cognitive factors are hard to derive from observation. In contrast, communicating persons usually have clear understanding whether they communicate or not, and such information is represented in their mindsets. This work investigates whether the mental processing of faces can be identified through means of a Passive Brain-Computer Interface (pBCI). This then could be used to support the cars' autonomous interpretation of facial mimicry of pedestrians to identify non-verbal communication. Furthermore, the attentive driver can be utilized as a sensor to improve the context awareness of the car in partly automated driving. This work presents a laboratory study in which a pBCI is calibrated to detect responses of the fusiform gyrus in the electroencephalogram (EEG), reflecting face recognition. Participants were shown pictures from three different categories: faces, abstracts, and houses evoking different responses used to calibrate the pBCI. The resulting classifier could distinguish responses to faces from that evoked by other stimuli with accuracy above 70%, in a single trial. Further analysis of the classification approach and the underlying data identified activation patterns in the EEG that corresponds to face recognition in the fusiform gyrus. The resulting pBCI approach is promising as it shows better-than-random accuracy and is based on relevant and intended brain responses. Future research has to investigate whether it can be transferred from the laboratory to the real world and how it can be implemented into artificial intelligences, as used in autonomous driving.

Although review writing is becoming increasingly relevant for theses-by-publication processes, the topic of review writing has hardly been empirically studied from the Ph.D. students’ perspective. This paper addresses this desideratum by providing results of an exploratory study on review writing in German sports science. Based on a social constructivist approach and a socialization theory frame, the study investigated complexes of themes and knowledge that characterize Ph.D. students‘ review writing as part of sports science doctoral qualification processes within theses-by-publication. Between January and March 2021, 20 Ph.D. students from different sports science subdisciplines were interviewed using expert interviews. A structured-thematic qualitative content analysis identified six main experiential fields of review writing (type of review, individual significance of the review in the doctoral process, approach to writing the review, acquisition of review writing as a method, opportunities in elaborating and publishing the review, and challenges in elaborating and publishing the review). The topics of the category system highlight the diversity of review writing experiences, which can be bundled as content-related, social, and affective dimensions of socialization processes. At the same time, the topics of the category system allow specifying three dimensions of the socialization process for (sports) scientific qualification processes. In this way, the perspective of Ph.D. students on review writing as a central scientific practice and part of the doctoral dissertation is fundamentally determined. This could represent a gain in knowledge for the future implementation of research projects on the doctoral culture within as well as outside of sports science.

The production of plastics from biological resources is a promising option for decarbonizing plastic production and solving the plastic waste issue. The current practice of using food plants such as corn as feedstocks however entails sustainability issues related to agricultural land use. Alternative feedstocks in the form of by-products have been explored for some time but are yet awaiting to reach the stage of market readiness. Lack of cost competitiveness has been identified as one major obstacle. This paper undertakes the first comparative meta-analysis of the costs of producing Polylactic Acid (PLA), a leading bio-based plastic polymer, from two alternative feedstocks: corn grain and corn stover. Cost contributions of specific inputs and process stages are identified through a production chain perspective. By applying the Monte Carlo technique for the first time within a bioplastic cost analysis, uncertainties in current estimates are reflected. As uncertainty factors, both technological input requirements and the development of input prices are considered. Despite higher energy requirements, we estimate that corn stover-based PLA is already competitive with corn grain-based PLA in terms of variable costs, resulting from the lower costs of feedstock procurement. However, this is overshadowed by the disadvantage of higher fixed costs. Our long-term analysis stresses the importance of lowering fixed unit costs through upscaling and associated learning effects. A major restriction to upscaling represents the demand side. To render production from alternative feedstocks competitive, it is crucial to inform consumers about the environmental superiority of such a feedstock switch.

BackgroundMortality after ST-elevation myocardial infarction (STEMI) is dependent from best-medical treatment after initial event.ObjectivesDetermining the impact of prescription of guideline-recommended therapy after STEMI in two cohorts, patients with and without history of arterial hypertension, on survival.Methods1,025 patients of the Cologne Infarction Model registry with invasively adjudicated STEMI were dichotomized according to their history of arterial hypertension. We recorded prescription rates and dosing of RAS-inhibitors, β-blockers and statins in all patients. The primary outcome was all-cause death. Mean follow-up was 2.5 years.ResultsMean age was 64 ± 13 years, 246 (25%) were women. 749 (76%) patients had a history of hypertension. All-cause mortality was 24.2%, 30-day and 1-year mortality was 11.3% and 16.6%, respectively. History of hypertension correlated with lower mortality (hazard ratio [HR], @30 days: 0.41 [0.27-0.62], @1 year: 0.37 [0.26-0.53]). After adjusting for age, sex, Killip-class, diabetes mellitus, body-mass index, kidney function and statin prescription at discharge 1-year mortality HR was 0.24 (0.12-0.48). At discharge, prescription rates for RAS-inhibitors, β-blockers and statins, as well as individual dosing and long-term persistence of RAS-inhibitors were higher in patients with history of hypertension. On the same lines, prescription rates for RAS-inhibitors, β-blockers and statins at discharge correlated significantly with lower mortality regardless of history of hypertension.ConclusionPatients with history of hypertension show higher penetration of guideline recommended drug therapy after STEMI, which may contribute to better survival. Better tolerance of β-blockers and RAS-inhibitors in patients with history of hypertension, not hypertension itself, likely explains these differences in prescription and dosing.

© 2016 Elsevier Inc. Sun-loving plants have the ability to detect and avoid shading through sensing of both blue and red light wavelengths. Higher plant cryptochromes (CRYs) control how plants modulate growth in response to changes in blue light. For growth under a canopy, where blue light is diminished, CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5. These factors are also known to be controlled by phytochromes, the red/far-red photoreceptors; however, transcriptome analyses indicate that the gene regulatory programs induced by the different light wavelengths are distinct. Our results indicate that CRYs signal by modulating PIF activity genome wide and that these factors integrate binding of different plant photoreceptors to facilitate growth changes under different light conditions.

ObjectiveTo describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum.MethodsHIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated.ResultsEighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was

Abstract Background Patient safety incidents defined as any unintended or unexpected incident that could have or were judged to have led to patient harm, are reported as relatively common. In this study patient complaints have been used as an indicator to uncover the occurrence of patient safety incidents in primary care emergency units (PCEUs) in Norway. Methods Ten PCEUs in major cities and rural parts of Norway participated. These units cover one third of the Norwegian population. A case-control design was applied. The case was the physician that evoked a complaint. The controls were three randomly chosen physicians from the same PCEU as the physician having evoked the complaint. The following variables regarding the physicians were chosen: gender, citizenship at, and years after authorization as physician, and specialty in general practice. The magnitude of patient contact was defined as the workload at the PCEU. The physicians’ characteristics and workload were extracted from the medical records from the fourteen-day period prior to the consultation that elicited the complaint. The rest of the variables were then obtained from the Norwegian physician position register. Logistic regression was used to estimate odds ratio for complaints both unadjusted and adjusted for the independent variables. The data were analyzed using SPSS (Version25) and STATA. Results A total of 78 cases and 217 controls were included during 18 months (September 1st 2015 till March 1st 2017). The risk of evoking a complaint was significantly higher for physicians without specialty in general practice, and lower for those with medium low and medium high workload compared to physicians with no duty during the fourteen-day period prior to the index consultation. The limited strength of the study did not make it possible to assess any correlation between workload and the other variables (physician’s gender, seniority and citizenship at time of authorization). Conclusions Continuous medical training and achieving the specialty in general practice were decisively associated with a reduced risk for complaints in primary care emergency services. Future research should focus on elements promoting quality of care such as continuing education, duty rosters and other structural and organizational factors.

Abstract Background Gastric cancer is one of the deadliest cancer entities worldwide. While surgery is the only curative treatment option in early tumors, for locally advanced and metastatic patients further therapeutic targets are needed. Several studies not only reported mutations but also amplifications of the KRAS locus in different cancer entities. More recently, KRAS amplification was discussed as a new therapeutic target. Little is known about the (prognostic) relevance and (heterogenic) distribution of KRAS amplification in gastric adenocarcinomas, especially in Non-Asian patients. Methods Amplification of the KRAS locus and corresponding protein expression was analyzed in 582 gastric adenocarcinomas employing fluorescence in-situ hybridization (FISH) and immunohistochemistry. Amplification status was correlated with clinico-pathological features, clinical outcome and molecular tumor data including a correlation to the TCGA subtypes of gastric carcinoma. Results KRAS amplification was detected in 27 out of 470 analysable tumors (5.7%) and correlated with protein expression of KRAS in all amplified tumors. Within the KRAS amplified gastric tumors 14/27 (51.9%) showed a heterogeneous distribution with also KRAS non-amplified tumor parts. According to TCGA 24 tumors (88.8%) were related to chromosomal instable tumors (CIN). The survival analysis of the entire patient cohort did not show any difference in overall survival in dependence on the KRAS status. However, a significant survival difference with a worse outcome for patients with KRAS amplified tumors was identified when analysing patients without neoadjuvant pre-treatment. Conclusions We confirm the unfavorable prognosis of KRAS amplified tumors reported by other studies in (Asian) patient groups, at least in patients without neoadjuvant pre-treatment. Within KRAS amplified tumors we revealed intratumoral heterogeneity that may define a (more aggressive) tumor cell population which is more frequently observed in patients with lymph node metastases. Despite the heterogeneous distribution of KRAS amplified tumor clones, KRAS amplified locally advanced or metastasized gastric adenocarcinomas represent a therapeutically highly relevant tumor subgroup.

Across Sub-Saharan Africa, agricultural practices for sustainable intensification need to be up-scaled from project interventions to institutional mainstreaming. However, several constraints, including a general lack of resources and knowledge, limited institutional support and challenging market conditions hamper this process. The objective of this study was to develop region-specific options to promote Conservation Agriculture (CA) in the Laikipia region, Kenya. We applied the Transformative Learning Approach (TLA) to stimulate and nurture a joint learning process around CA, to diagnose hindering and supporting factors for up-scaling of CA and to develop options for change promotion. Through a series of field visits, we collected and analyzed data using elements of the TLA approach: i.e. agro-ecosystem health check, stakeholder mapping, participatory videos and the Qualitative Assessment tool for CA adoption (QAToCA). Our findings reveal that up-scaling of CA is hindered by inefficient agricultural market structures, limited access to CA specific biological (residue, seeds), and technical inputs (e.g. machinery), a lack of finances, and absence of knowledge. We recommend four options for further CA promotion in the region: localised expertise (e.g. crop-livestock integration), unbiased facilitation (e.g. careful choice of multipliers), subsidized inputs (e.g. micro-credits) and robust institutional system support (e.g. stable agricultural policies).

Hypolimnetic anoxia in eutrophic lakes can delay lake recovery to lower trophic states via the release of sediment phosphorus (P) to surface waters on short timescales in shallow lakes. However, the long-term effects of hypolimnetic redox conditions and trophic state on sedimentary P fraction retention in deep lakes are not clear yet. Hypolimnetic withdrawal of P-rich water is predicted to diminish sedimentary P and seasonal P recycling from the lake hypolimnion. Nevertheless, there is a lack of evidence from well-dated sediment cores, in particular from deep lakes, about the long-term impact of hypolimnetic withdrawal on sedimentary P retention. In this study, long-term sedimentary P fraction data since the early 1900s from Lake Burgäschi provide information on benthic P retention under the influence of increasing lake primary productivity (sedimentary green-pigment proxy), variable hypolimnion oxygenation regimes (Fe∕Mn ratio proxy), and hypolimnetic withdrawal since 1977. Results show that before hypolimnetic withdrawal (during the early 1900s to 1977), the redox-sensitive Fe∕Mn-P fraction comprised ∼50 % of total P (TP) in the sediment profile. Meanwhile, long-term retention of total P and labile P fractions in sediments was predominantly affected by past hypolimnetic redox conditions, and P retention increased in sedimentary Fe- and Mn-enriched layers when the sediment-overlaying water was seasonally oxic. However, from 1977 to 2017, due to eutrophication-induced persistent anoxic conditions in the hypolimnion and to hypolimnetic water withdrawal increasing the P export out of the lake, net burial rates of total and labile P fractions decreased considerably in surface sediments. By contrast, refractory Ca–P fraction retention was primarily related to lake primary production. Due to lake restoration since 1977, the Ca–P fraction became the primary P fraction in sediments (representing ∼39 % of total P), indicating a lower P bioavailability of surface sediments. Our study implies that in seasonally stratified eutrophic deep lakes (like Lake Burgäschi), hypolimnetic withdrawal can effectively reduce P retention in sediments and potential for sediment P release (internal P loads). However, after more than 40 years of hypolimnetic syphoning, the lake trophic state has not improved nor has lake productivity decreased. Furthermore, this restoration has not enhanced water column mixing and oxygenation in hypolimnetic waters. The findings of this study are relevant regarding the management of deep eutrophic lakes with mixing regimes typical for temperate zones.

Tumor lysis syndrome (TLS) is a potentially life-threatening complication of chemotherapy. It usually occurs in rapidly proliferating hematological malignancies. TLS is deemed spontaneous (STLS) when it occurs prior to any cytotoxic or definite treatment. STLS is extremely rare in solid tumors. Here, we report a rare case of fatal STLS in a 47-year-old woman diagnosed with metastatic colon cancer. The patient developed acute renal failure with anuria, electrolyte disturbances, and metabolic acidosis before initiating chemotherapy. Despite appropriate management of TLS, including renal replacement therapy, she died within a few days from multiorgan failure. Only few other case reports of STLS associated with colon cancer have been reported in the literature.

Gene amplifications of PIK3CA or KRAS induce a downstream activation of the AKT-mTOR or RAF-ERK-pathways. Interactions of the active AKT pathway have been implicated in the inflammatory tumor microenvironment. Nothing is known about these interactions or prognostic power in esophageal adenocarcinoma (EAC). We retrospectively analyzed a large cohort of 685 EAC considering KRAS and PIK3CA gene amplification using fluorescence in situ hybridization (FISH) and immunohistochemistry. These results were correlated with clinical and molecular data as well as the inflammatory tumor microenvironment. Amplifications of KRAS were seen in 94 patients (17.1%), PIK3CA amplifications in 23 patients (5.0%). KRAS amplifications significantly correlated with nodal positive patients and poorer overall survival (OS) in the subgroup without neoadjuvant treatment (p = 0.004), coamplifications of Her2 (p = 0.027), and TP53 mutations (p = 0.016). PIK3CA amplifications significantly correlated with a high amount of tumor infiltrating T cells (p = 0.003) and showed a tendency to better OS (p = 0.068). A correlation with checkpoint makers (PD-L1, LAG3, VISTA, TIM3, IDO) could not be revealed. Our findings are the first to link the KRAS amplified genotype with lymphonodal positivity and poor prognosis and the PIK3CA-amplified genotype with a T cell–rich microenvironment in EAC. Future studies must show whether these two genotype subgroups can be therapeutically influenced. A dual inhibition of MEK and SHP2T could be effective in the subgroup of KRAS amplified EACs and an immune checkpoint blockade may prove to be particularly promising in the subgroup of PIK3CA-amplified EACs.

Abstract Background The SWI/SNF complex is an important chromatin remodeler, commonly dysregulated in cancer, with an estimated mutation frequency of 20%. ARID1A is the most frequently mutated subunit gene. Almost nothing is known about the other familiar members of the SWI/SNF complexes, SMARCA2 (BRM), SMARCA4 (BRG1) and SMARCB1 (INI1), in oesophageal adenocarcinoma (EAC). Methods We analysed a large cohort of 685 patients with EAC. We used four different antibodies to detect a loss-of-protein of ARID1A BRM, BRG1 and INI1 by immunohistochemistry and correlated these findings with molecular and clinical data. Results Loss of ARID1A, BRG1, BRM and INI1 was observed in 10.4, 3.4, 9.9 and 2% of EAC. We found a co-existing protein loss of ARID1A and BRM in 9.9% and of ARID1A and BRG1 in 2.2%. Patients with loss of ARID1A and TP53 wildtype EACs showed a shortened overall survival compared with AIRDA1A-positive tumours [median overall survival was 60.1 months (95%CI 1.2–139.9 months)] in patients with ARIDA-1A expression and 26.2 months (95%CI 3.7–19.1 months) in cases of ARIDA-1A loss (p = 0.044). Tumours with loss or expression of ARID1A and TP53 loss were not associated with a difference in survival. Only one tumour revealed high microsatellite instability (MSI-H) with concomitant ARID1A loss. All other ARID1A loss-EACs were microsatellite-stable (MSS). No predictive relevance was seen for SWI/SNF-complex alterations and simultaneous amplification of different genes (PIK3CA, KRAS, c-MYC, MET, GATA6, ERBB2). Conclusion Our work describes, for the first time, loss of one of the SWI/SNF ATPase subunit proteins in a large number of adenocarcinomas of the oesophagus. Several papers discuss possible therapeutic interventions for tumours showing a loss of function of the SWI/SNF complex, such as PARP inhibitors or PI3K and AKT inhibitors. Future studies will be needed to show whether SWI/SNF complex-deficient EACs may benefit from personalized therapy.

Goal: Retinal prosthesis performance is limited by the variability of elicited phosphenes. The stimulating electrode's position with respect to retinal ganglion cells (RGCs) affects both perceptual threshold and phosphene shape. We created a modeling framework incorporating patient-specific anatomy and electrode location to investigate RGC activation and predict inter-electrode differences for one Argus II user. Methods: We used ocular imaging to build a three-dimensional finite element model characterizing retinal morphology and implant placement. To predict the neural response to stimulation, we coupled electric fields with multi-compartment cable models of RGCs. We evaluated our model predictions by comparing them to patient-reported perceptual threshold measurements. Results: Our model was validated by the ability to replicate clinical impedance and threshold values, along with known neurophysiological trends. Inter-electrode threshold differences in silico correlated with in vivo results. Conclusions: We developed a patient-specific retinal stimulation framework to quantitatively predict RGC activation and better explain phosphene variations.

Young farmers play a significant role in sustaining food security and the communities’ and rural areas’ viability. However, as with many countries, Thailand is facing a decline in the number of young farmers who, if not productive and satisfied with their farm business, are likely to exit farming to take advantage of their increased educational level and off-farm job opportunities. Data were collected by interviewing young farmers in the Prachin Buri province, Thailand, with the aim of assessing their reason for farming in the long-term and the type of farming. Farming decisions can be categorised into three types: full-time profit-oriented farming with a focus on rice production (~53%), full-time multifunctional farming in innovative mixed or organic production systems (~23%), and part-time farming where young farmers work off-farm and farm outside regular working hours (~24%). Using path analysis, we investigated which physical and psychological factors affect young farmers’ decisions to pursue these three farming types. The results show that non-monetary farming’s benefits are as important as monetary benefits. Education, farming and regular off-farm work experience, farm production, market and pest problems, and government support directly affect the farming types. These effects were also mediated by attitudes towards farming and net farming income. Young farmers choosing to pursue multifunctional farming have higher incomes, more often apply sophisticated technologies, and farm more sustainably than those choosing the other types of farming. This indicates that a shift from conventional rice production to more diversified production systems using innovative technologies is needed to sustain farming success and retain young people in the farming sector.

PurposeResults from large scale cardiovascular outcome trials in patients with type 2 diabetes mellitus (DM2) have found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular death and hospitalization for heart failure, but the mechanisms behind the beneficial cardiovascular effects are not fully understood. We tested the hypothesis that the SGLT2i, empagliflozin, improves non-endothelial dependent coronary microvascular function, thereby leading to better cardiac function.MethodsPatients with DM2 followed at the endocrinology outpatient clinic at Bispebjerg University Hospital were included in a double blinded, placebo-controlled cross-over study. Participants were allocated equally to each treatment sequence using simple randomization and treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Echocardiographic parameters of cardiac function were measured, and blood samples were analyzed for a broad panel of cardiovascular biomarkers.ResultsThirteen patients were randomized to each sequence and 10 and 9 completed the study according to protocol, respectively, and were included in the analysis of outcome parameters. We found no improvement in CFVR (change in the empagliflozin period was -0.16 (SD 0.58)). There were no effects on cardiac systolic function or indicators of cardiac filling pressure. Well-known effects of empagliflozin were obtained, such as weight loss and reduction in Hba1c level. Creatinine level increased but remained within normal range. We observed a clear trend of reduction in cardiovascular biomarkers after empagliflozin treatment and increased levels after the placebo period. No serious adverse reactions were reported.ConclusionsDespite effect on weight-loss, Hba1c and biomarkers, treatment with empagliflozin for 12 weeks did not improve CFVR in patients with DM2.

A tunable vacuum-ultraviolet (VUV) laser source based on four-wave frequency mixing in xenon is presented. Using seed radiation from two continuous-wave lasers, the system allows for precise control of the VUV frequency and is developed for the resonant laser excitation of the Th-229 nucleus to its low-energy isomeric state. The system is prepared to operate in a wide scanning range from 148 nm to 155 nm. The source produces pulses of 6–10 ns duration with up to 40 µ J energy and is coupled via a vacuum beamline to a linear radiofrequency ion trap. In a first implementation of VUV laser spectroscopy of trapped Th ^+ ions we excite three previously unknown resonance lines near 149 nm wavelength to electronic levels that are close to the Th-229 isomer energy. The resonances are detected and analyzed via fluorescence of the excited Th ^+ ions. An analysis of the lineshape is used to estimate the linewidth of the VUV radiation to be in the range of $\leqslant$ 6 GHz, dominated by phase noise that is enhanced in harmonic generation and in the four-wave mixing process. The prospects for the use of the system in nuclear laser spectroscopy of Th-229 are discussed.

Microstructure optimization of Al-Zn-Mg-Cu-Zr aluminum alloys, particularly through recrystallization inhibition, for improved strength and corrosion resistance properties has been an important consideration in alloy development for aerospace applications. Addition of rare earth elements, sometimes combined with Cr, has been found to be beneficial in this regard. In this study, the role of a single addition of 0.1 wt.% Cr on microstructure evolution of an Al-Zn-Mg-Cu-Zr (7449) alloy during processing was systematically investigated by optical light microscopy, scanning electron microscopy, electron backscatter diffraction and scanning transmission electron microscopy. Susceptibility to localized corrosion after aging to T4, T6 and T76 conditions was evaluated by potentiodynamic polarization (PDP) measurements and an intergranular corrosion (IGC) test. A decrease in recrystallized fraction with 0.1 wt.% Cr addition was observed, which is attributed to the formation of Cu- and Zn-containing E (Al18Mg3Cr2) dispersoids and the larger as-cast grain size. Moreover, the depletion of alloying elements from solid solution due to the formation of the Cu- and Zn-containing E (Al18Mg3Cr2) dispersoids and η Mg(Zn,Cu,Al)2 phase at its interface affects grain-boundary precipitation. The observed decrease in localized corrosion susceptibility with minor Cr addition is correlated with the microstructure and equally discussed.