Academic literature on the topic '3-4 year cycles'

This study aims to determine the discipline of children at KB Puri Siwi Tamansari Academic Year 2016/2017 and find out the improvement of children's discipline through playing traffic simulations at KB Puri Siwi Tamansari Academic Year 2016/2017. This research method uses a type of classroom action research. This research was conducted in two stages, namely cycle I and cycle II. The subjects of this study were Puri Siwi Play Group students aged 3-4 years Tamansari Tlogowungu Pati as many as 16 students. The results of this study indicate that traffic simulations to improve child discipline are carried out with two cycles, the first cycle is carried out by simulating traffic signs with micro equipment, sikus II is carried out by simulating traffic signs with macro equipment. The results of data analysis and observations through traffic simulations showed an increase from the pre-cycle of 30% of children who completed their discipline, rising in the first cycle to 56.7%. That is, an increase of 24%. And in the second cycle increased to 81% and an increase of 25%. The results achieved in the second cycle had met the intended completeness target, namely 80% of all children scored with a complete category of 85. This increase in the average value proved the success of traffic simulations can improve children's discipline.

This study aims to determine the naturalist intelligence of children aged 3-4 years in Amanah Family Planning Guwo Tlogowungu Pati 2016/2017 academic year. 2) and to determine the increase in naturalist intelligence of children aged 3-4 years in Amanah Guwo KB Tlogowungu Pati 2016/2017 school year through area-based creative play. This research method uses a type of classroom action research. This research was conducted in two stages, namely cycle I and cycle II. The subjects of this study were students of Amanah Play Group aged 3-4 years Guwo Tlogowungu Pati as many as 20 students. The results of this study indicate that area-based creative play to improve children's naturalist intelligence is carried out with two cycles, the first cycle is carried out by opening 4 areas. The second cycle is done by opening 5 game areas. The results of data analysis and observation through area-based creative play showed an increase from the pre-cycle of 35% of children who completed their naturalist intelligence, increasing in the first cycle to 61%. That is, an increase of 30%. In cycle II it increased to 80% and there was an increase of 85%. The results achieved in the second cycle had fulfilled the intended completeness target, namely 80% of all children scored with a complete category of 85. This increase in the average value proved the success of area-based creative play to improve children's naturalist intelligence.

We investigated the dynamic properties of population cycles in Canadian muskrats (Ondatra zibethicus). Ninety-one historic time series of muskrat-harvest data obtained from the Hudson's Bay Company Archives were analyzed. Most series were 25 years in length (1925–1949) and were distributed primarily throughout five ecozones. For each series, we estimated period length and coefficients for a second-order autoregressive model. Estimated period length varied between 3 and 13 years, with 3- to 5-year periods located in Subarctic-Arctic ecozones. We hypothesize that the 4-year cycles are largely a result of predation by red fox (Vulpes vulpes), which exhibit 4-year cycles in Arctic regions. The remaining ecozones generally averaged 8–9 years in period length. However, the relative contributions of direct and delayed density dependence varied along a latitudinal gradient. We hypothesize that both social and trophic interactions are necessary to produce the observed dynamics, but that shifts in the nature of mink predation were responsible for the changes in the relative contribution of direct and delayed density dependence. Essentially, there is a tension between population-intrinsic and trophic interactions that may bound the length of the cycle.

In this paper we explore the cyclic interactions of prey–predator systems by examining the relationship between cycle lengths of both species and the strength of their interaction. As a probe of interaction strength, we use the degree of counter-clockwise rotation in phase plots with the prey on the x axis and the predator on the y axis. We compare the results from a 25-year time series from the Hudson’s Bay Company data on American mink ( Neovison vison (Schreber, 1777)) and muskrat ( Ondatra zibethicus (L., 1766)) with results from three simulation models. We found that the strength of interaction (rotation range: –0.4 to 1.1 rad/year) was strongest when the two cycle lengths were similar and that it increased with the amplitude of the cycles (cycle range: 4–10 years). The time difference between prey and predator cycles that corresponded to the highest interaction strength was 2–3 years. Similar results were obtained with simulation models; the most complex Hanski model showing the overall best fit with observations. However, none of the models were able to reproduce long ranges of stable cycles by only changing one of their parameters at a time (ranges 2–4 years), whereas the observed range of stable cycles was 4–10 years.

Abstract Frequently recurrences and progressive resistance to chemotherapy characterize indolent lymphomas. The use of anthracyclines has been improved the response rate and the disease free survival, however, its use in elderly patients is controversial because the related toxicities. We analyze the use of a chemotherapy regimen with a short course of anthracycline. Material and Methods: We included patients with untreated indolent lymphomas according to the WHO classification. The chemotherapy regimens were 3 cycles of CNOP (cyclophosphamide 600 mg/m2 day 1, mitoxantrone 10 mg/m2 day1, vincristine 1.4 mg/m2 day 1 and prednisone 50 mg/m2 days 1–5) every 21 days, followed by 4 cycles of COPB (cyclophosphamide 800 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, a bleomycin 10 U/m2 day 1 and prednisone 50 mg/m2 days 1–5) every 14 days. Results: In an intent to treat 75 patients were valuable, 37 females and 38 males, median age was 56 (range 28–84), the histological variants were: follicular grade 1 and 2 (45 patients), lymphoma/leukemia of small well differentiated lymphocytes (6 patients), mantle cell lymphoma (1 patient), nodal marginal zone lymphoma (4 patients), lymphoplasmocytic lymphoma (1 patient), indolent lymphoma not otherwise characterized (12 patients), 61 patients (81.3%) had bulky disease, 57 patients (76%) had advanced disease (stage III and IV). According to the IPI: low risk (28 patients), low intermediate (21 patients), high intermediate (14 patients), and high (12 patients). A total of 488 cycles were administrated, 82 (16.8%) cycles had hematologic toxicities: 30 cycles grade 1, 29 cycles grade 2, 18 cycles grade 3, and 5 cycles grade 4. Filgrastim was needed in 20 patients (43 cycles). 58 patients had gastrointestinal toxicity (29 grade1, 26 grade 2, 3 grade 3), 61 patients had neurological toxicity (47 grade 1, 13 grade 2, 1 grade 3). 14 patients (18.7%) required hospitalization, 7 patients due to toxicity related chemotherapy and 6 due to tumor progression. The overall response rate was 84% (63 patients): Complete response 33 patients (44%), unconfirmed complete response 6 patients (8%), partial response 24 patients (32%). Failure to treatment occurred in 11 patients (14.7%). Adding radiotherapy 12 more patients were converted to complete response for a total of 45 patients (60%). With a median of follow up of 24 months (range 3–62 months) 10 patients (13.3%) relapsed, 13 (17.3%) patients died (8 due to tumor progression and 3 related to toxicity of the regimen). The actuarial 5-year disease free survival was 71% and the overall survival 86%. Conclusions: This chemotherapy regimen provides an effective alternative for the treatment of indolent lymphomas even in advanced or bulky disease. This regimen is well tolerated for elderly patients and has a good safety profile. It is necessary a long time of follow up to establish the importance of the regimen in free disease survival and in overall survival.

Abstract. An examination of the maximum yearly values of the conventional sunspot number Rz of all cycles revealed fluctuations of various intervals in the high periodicity region (exceeding 11 years), namely 2 cycles (Hale, 22 years), 3 cycles (TRC, three-cycle) and longer intervals. The 2-cycle spacings had the smallest amplitudes. According to the G-O (Gnevyshev-Ohl) rule (Gnevyshev and Ohl, 1948), the even-numbered series of the maxima of annual mean Wolf sunspot numbers Rz are followed by higher amplitude odd-numbered series. Kopecky (1950) generalized this relation to annual mean Wolf numbers corresponding to equivalent phases of the adjacent even-odd 11-year cycles. Therefore, we would call it the G-O-K rule. For the data of 28 cycles (cycle −4 to cycle 23), it was found that four pairs (~29%) from the fourteen even-odd pairs showed failure of the G-O-K rule. In the remaining ten pairs, the magnitudes of the odd cycles were well-correlated with the magnitudes of the preceding even cycles, but it was impossible to tell whether it would be a normal pair following the G-O-K rule or a possible case of failure. A much stronger sequence was the three-cycle sequence (TRC, low, high, higher). The 2-cycle oscillations were embedded into the TRC until the G-O-K rule failures occurred as in cycle 23. The patterns of cycle 17 (low), 18 (high), 19 (higher); 20 (low), 21 (high), 22 (higher) were noticed and used by Ahluwalia (1995, 1998) to predict a low value for cycle 23, which was accurate. However, in the earlier data, the preceding sequence (14, 15, 16) was rather uncertain, and before that for seven cycles (cycles 8-14), there were no TRC sequences at all. During the twelve cycles −4 to 7, there were only three isolated TRC sequences (one doubtful). In view of this chequered history of TRC, it is doubtful whether the present TRC pattern (cycles 17–23) would persist in the near future. Spectral analysis showed that in the first half (cycles −4 to 9), larger periodicities (reminiscent of the Gleissberg cycle of ~80 years) prevailed. but in the latter half, periodicities were different (3-year cycle was predominant) and the matching was not good. In particular, the points for the recent cycles 21, 22 seemed to deviate considerably from the constructed series, thus introducing unreliability in predictions for the future by using extrapolation of periodicities.

9559 Background: Kaposi’s sarcoma is the most common malignancy among HIV patients and is considered to be one of the AIDS defining conditions. This abstract illustrates our 10 year experience with the treatment of 32 Kaposi’s sarcoma HIV patients with the same therapeutic approach. Methods: Between 04/95 and 03/05 we recruited 32 previously untreated patients that were diagnosed with Kaposi’s sarcoma and treated at the Servicio de Oncologia Clinica (Universitary Clinicas Hospital) in Montevideo. All of them received the same iv polychemotherapy plan (Adriamycin 10mg/m2, Bleomycin 10 U/m2 and Vincristine 1.4 mg/m2, every two weeks until tumor progression or severe toxicity). Results: 21 of the patients were good risk ones and the remaining 11 were poor risk patients (AIDS Clinical Trials Group staging classification). CD4 levels varied from 6 to 780/ml and the viral load ranges were 240 to 89000 copies. The patients received an average of 10.2 (4–21) polychemotherapy cycles. Grade 3–4 myelotoxicity was reported in 5 patients delaying the onset of the subsequent cycles. Grade 2 neurotoxicity was seen in 7 patients after 4, 5, 6, 8, 10, 11 and 13 cycles of ABV, changing vincristine for vinblastine (4mg/m2 every two weeks) in these patients. All the patients achieved a partial response with improvements in CD4 levels and viral load. 13/32 patients experienced a relapse (3–29 months after last chemotherapy cycle). 3 patients were retreated with paclitaxel 135 mg/m2 with 2/3 new partial responses of shorter duration. 5 patients received 4 additional ABV cycles achieving a new partial response. 5 patients refused further treatment dying due to progressive disease. One relapsed patient developed a second malignancy (High grade Non Hodgkin lymphoma) dying three months later. Conclusions: These data suggest that ABV regimen is still an effective treatment option for HIV-Kaposi’s sarcoma, specially in the undeveloped countries in which the cost of other better internationally approved options (liposomal doxorubicin and daunorubicin) makes them unaccesible for the majority of the population. No significant financial relationships to disclose.

6528 Background: Small benefits are judged sufficient to make ACT worthwhile by women who have had either 6 cycles of CMF or 4 cycles of AC. We sought to determine the benefits needed to make longer and more intensive regimens worthwhile. Methods: 293 women who completed ACT 3 to 39 months earlier were presented 4 hypothetical scenarios based on known survival times (5 and 15 years) and rates (65% and 85% at 5 years) without ACT using validated, standardised interviews. 179 were in a randomized trial (BIG 02–98) testing addition of docetaxel (T) to a standard regimen including doxorubicin (A) and classical CMF; 114 were treated outside of the trial at the same centres. Women also rated their recollections of health-related quality of life during ACT. Results: The median age was 55 (range 25 to 78), 36% had a college or university degree, and 62% had dependants. The regimens (and their duration) in the trial were: 4 cycles of A or AC then 3 cycles of CMF (24w) in 31% of the women; 4 cycles of AT followed by 4 cycles of CMF (24w) in 29%; and 3 cycles of A then 3 cycles of T then 3 cycles of CMF (30w) in 40%. The regimens outside of the trial were: 4 cycles of AC (12w) in 52%; 6 cycles of CMF (24w) in 20%; and 4 cycles of AC then 3 cycles of CMF (24w) in 23%. A 2% gain in 5-year survival rates or a 6-month gain in survival duration was judged sufficient to make ACT worthwhile by 62–67% of women. Gains of more than 5% in 5-year survival rates or more than 2 years in survival duration were judged necessary to make ACT worthwhile by 10–20% of women. Women's preferences were strongly associated with the aversiveness of their treatment. Women who had more problems with physical well-being, coping with treatment, and nausea or vomiting judged larger benefits necessary to make their ACT worthwhile (p<.0001). Preferences were unaffected by chemotherapy regimen, duration, context in a trial, age, time between treatment and interview, and social circumstances (p>.2). Conclusions: As in previous studies, small benefits were judged sufficient to make ACT worthwhile, even if it lasted 6–7 months, and included docetaxel, doxorubicin and CMF. No significant financial relationships to disclose.

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

Bank voles, grey-sided voles, and field voles had synchronous 3-4 year density cycles with variable amplitudes which averaged about 200-fold in each species. Cycles of vole predators (red fox and Tengmalm's owl), and their (foxes') alternative prey (mountain hare and forest grouse) lagged behind the vole cycles. The nomadic Tengmalm's owl responded with a very rapid and strong numerical increase to the initial cyclic summer increase of voles (the owl’s staple food). Owl breeding densities in the springs were highly correlated with vole supply in the previous autumns. This suggested that the number of breeding owls was largely determined in the autumn at the time of the owl's nomadic migrations, and that immigration was crucial for the rapid rise in owl numbers. The owl's numerical response was reinforced by the laying of earlier and larger clutches when food was plentiful. In addition, the owl has an early maturation at one year of age. The transition between subsequent vole cycles was characterized by a distinct shift in rate of change in numbers from low to high or markedly higher values in both summer and winter. Regulation increased progressively throughout the cycle since the rate of change decreased continuously in the summers. Moreover, there was a similar decrease of the rate of change in winter. Rate of change was delayed density-dependent. The delayed density-dependence had an 8 month time-lag in the summers and a 4 month time-lag in the winters relative to the density in previous autumns and springs, respectively. These findings suggest that vole cycles are likely to be generated by a time-lag mechanism. On theoretical grounds, it has been found that a delayed density- dependence of population growth rate with a 9 month time-lag caused stable limit cycles with a period between 3 and 4 years. Some mechanisms for the delayed density-dependence are suggested and discussed. The mechanisms are assumed to be related to remaining effects of vole populations past interactions with predators, food supplies, and/or diseases. Unlike the other voles, the bank vole had regular and distinct seasonal declines in density over winter. These declines are proposed to be due to predation, mainly by Tengmalm's owl. Supranivean foraging for epiphytic tree lichens and conifer seeds most likely explains why this species was frequently taken by the owl under snow-rich conditions. The alternative prey hypothesis predicts that a reduction of predator numbers should increase the number of alternative prey. Alternative prey should be less effectively synchronized to the vole cycle by predation at declining and low vole (main prey) densities; they may also lose their 3-4 year cyclicity. The appearance of sarcoptic mange among foxes in northern Sweden in the mid 1970s provided an opportunity to "test" these ideas, and these were found to be supported. In areas with highest mange infection rates, foxes declined markedly from the late 1970s to mid 1980s, whereas hare numbers rose rapidly and appeared non-cyclic.

Diss. (sammanfattning) Umeå : Umeå universitet, 1991, härtill 7 uppsatser

digitalisering@umu

Testicular germ cell tumours represent the most common solid neoplasms in the age group of 20 to 40 years. These cancers have an excellent prognosis, with a 90% long-term survival rate due to well-established, interdisciplinary guidelines for diagnosis and treatment. Independent on the clinical stage at time of diagnosis, treatment after orchidectomy is performed on an individual risk adapted approach. In clinical stage I seminoma, active surveillance is the recommended therapy and adjuvant chemotherapy with carboplatin remains an option in men not suitable for surveillance. Clinical stage IIA/B and IIC are treated by radiation therapy and by systemic chemotherapy following orchidectomy. Clinical stage I non-seminomas are either treated by active surveillance or by one cycle of adjuvant PEB chemotherapy. Clinical stages IIA-C and advanced stages of GCT are treated by 3-4 cycles of PEB chemotherapy depending on IGCCC risk profile. Relapsing cases should be treated at tertiary referral centres only.

This GSoD In Focus aims at providing a brief overview of the state of democracy in Europe at the end of 2019, prior to the outbreak of the pandemic, and then assesses some of the preliminary impacts that the pandemic has had on democracy in the region in the last 10 months. Key facts and findings include: • The COVID-19 pandemic arrived in a largely democratic Europe. Only 4 countries in the region (10 per cent) are not democracies, while many of the democracies are high performing. • Democracy in Europe, however, has in recent years experienced erosion and backsliding. More than half of European democracies have eroded in the last 5 years. In particular, 3 countries—Hungary, Poland and Serbia—have registered a more severe form of erosion, called democratic backsliding, with Hungary regressing on its democratic standards for the past 14 years. • The pandemic has intensified these pre-existing concerns. The 3 backsliding countries in Europe have implemented a number of measures to curb the pandemic that are concerning from a democracy standpoint. • The main democratic challenges caused by the pandemic in Europe pertain to the disruption of electoral cycles, curtailment of civil liberties, the use of contact tracing apps, the increase in gender inequality and domestic violence, risks to vulnerable groups, executive aggrandizement, protest waves, corruption cases and challenges in the relationship between local and national governance. • Europe’s democracies have mostly showed resilience, and opportunities for furthering the integrity of elections, for digitalization and for innovative social protests have arisen. The review of the state of democracy during the COVID-19 pandemic in 2020 uses qualitative analysis and data of events and trends in the region collected through International IDEA’s Global Monitor of COVID-19’s Impact on Democracy and Human Rights, an initiative co-funded by the European Union.

The spruce needleminer, Epinotia tedella (Cl.) (Lepidoptera: Tortricidae), is a small and abundant moth associated with Norway spruce (Picea abies Karst.). Larvae mine spruce needles, usually those more than 1 year old, and each requires about 35 needles to meet its food demands. In central Europe, the spruce needleminer is regarded as a temporary, serious pest when densities reach several thousand per square meter. However, it seldom causes significant damage in Scandinavian countries. An exception was the heavy infestation in southern Denmark in 1960-61. The spruce needleminer has one generation per year. Adults emerge in June and deposit eggs singly on spruce needles. Larvae mine the needles from July through October and then descend on silken threads in November to hibernate in the forest litter as prepupal larvae in cocoons. Pupation occurs in early May and lasts 3-4 weeks. Like many other forest defoliators, spruce needleminers are associated with a diverse fauna of parasitic Hymenoptera (parasitoids) (Münster-Swendsen 1979). Eggs are attacked by a minute wasp (Trichogramma sp.) that kills the embryo and emerges as an adult a few weeks later. Because spruce needleminer eggs have all hatched by this time, the parasitoids must oviposit in the eggs of other insect species. In other words, this parasitoid is not host-specific and therefore not expected to show a numerical response to spruce needleminer population changes. Newly hatched moth larvae immediately bore into needles and, because of this, are fairly well protected against weather and predators. However, specialized parasitic wasps (parasitoids) are able to deposit their eggs inside a larva by penetrating the needle with their ovipositor. Two species, Apanteles tedellae (Nix.) and Pimplopterus dubius (Hgn.), dominate the parasitoid guild and sometimes attack a large percentage of the larvae (Münster -Swendsen 1985). Parasitized larvae continue to feed and, in November, descend to the forest floor to overwinter with unparasitized individuals. In late April, however, the parasitoids take over and kill their hosts. Besides mortality from endoparasitoids, up to 2% of the larvae die within the mine due to an ectoparasitoid and a predatory cecidomyid larva.

Extreme, regional droughts are the most common form of disturbance in semiarid ecosystems typified by relatively slow recovery rates. Drought-driven impacts can include regionally synchronized insect outbreaks, wildfires, and tree mortality (Swetnam and Betancourt 1990), as well as disastrous failures of agriculture, silviculture, and livestock production (Mainguet 1994). Drought conditions, accompanied by anthropogenic land mismanagement, have led to subsequent invasions of grasslands and farmlands by woody shrubs and nonnative forbs and grasses, contributing to the modern “desertification” process manifested in many parts of the world (Archer et al. 1988). In the American Southwest, the drought of the 1950s was one of the most severe climate events of the past millennium because of wide ramifications for the region’s ecology (Herbel et al. 1972; Swetnam and Betancourt 1998), water resources (Thomas 1963), and economy (Regensberg 1996). As human population and resource needs increase in the Southwest, so will the economic sensitivity to largescale drought. A clear understanding of extreme droughts is necessary not only to understand long-term ecosystem dynamics, but also to mitigate socioeconomic impacts. The goals of this chapter are to use the Sevilleta LTER site in central New Mexico to (1) quantify the decadal variability in precipitation inferred from a 394-year record of tree rings, (2) relate the repeated decadal fluctuations in precipitation to major droughts of the 1890s and 1950s, (3) assess the ecological responses associated with droughts of the last century, and (4) elucidate the biotic-atmospheric feed backs that may influence future responses. We assess the magnitude, timing, and consequences of decadal fluctuations in annual precipitation. The Sevilleta LTER research site is located at the Sevilleta National Wildlife Refuge (NWR), Socorro County, New Mexico (34º20' N, 106º50' W). The Sevilleta NWR comprises 100,000 ha of grassland, desert, and woodland bordered by two mountain ranges and the Rio Grande Valley in between. Elevations range from 1,350 m at the Rio Grande to 2,797 m at Ladrón Peak in the northwestern portion of the refuge. Topography, geology, soils, and hydrology, interacting with major air mass dynamics, provide a spatial and temporal template that makes the region a transition zone between several biomes. The region contains communities that both represent and intersect Great Plains Grassland, Great Basin Shrub-steppe, Chihuahuan Desert, Interior Chaparral, and Montane Coniferous Forest (Brown 1982).

In the early years of the next regime, conservative courts will face off against liberal Democratic politicians. Courts are very unlikely to be able to do much to repair constitutional rot. Constitutional renewal must come from popular mobilizations and demands for reform, including constitutional reform. Growing frustration with the courts will lead to calls for reform of the federal judiciary. Reforms should aim at lowering the stakes of judicial appointments and assisting depolarization. Court-packing proposals achieve neither goal. Three better approaches are (1) instituting regular appointments to the Supreme Court; (2) achieving the equivalent of term limits for Supreme Court justices by changing quorum rules; (3) increasing the Court’s workload (instead of limiting its jurisdiction); and (4) using sunrise provisions that take effect in the future so that partisan advantages are harder to predict. Each of these proposals can be implemented constitutionally through ordinary legislation.

“Misfitting in America” offers an analysis of The Man Who Laughs that suggests the film’s importance in four key areas: (1) as a transitional piece between silent cinema and the talkies, (2) as the last instalment of the Universal super productions, (3) as a thematic precursor to Universal’s famous horror cycle, and (4) as one of the most complete Hollywood attempts to adopt and co-opt German filmmaking practices and personnel. Moreover, this chapter focuses on the star of The Man Who Laughs, Conrad Veidt, as representative of an exilic body. Analysing Veidt’s physicality, performance, makeup, and costuming as Gwynplaine, this contribution looks at the corporeal inscription of the character’s permanent disfiguration, which underpins Gwynplaine’s understanding of himself and his peripheral position in society. With its intrinsic linking of disfigurement and dislocation in an endless cycle where one leads seamlessly into the other, the film becomes a way to understand how Hollywood studios situated their European émigré stars in the years following World War I.

Caries is a chronic disease. If it starts to affect the permanent teeth the child patient is drawn into a cycle requiring ongoing care for the rest of his/her life. Therefore when treating the young permanent dentition we have to adopt an approach that considers and addresses the whole disease process and not just treat the outcome of the disease. Caries is still a considerable problem in children and adolescents. The 2013 Child Dental Health Survey for England, Wales, and Northern Ireland found that, on average, nearly half (46%) of 15-year-olds and a third (34%) of 12-year-olds had obvious decay experience. Although the proportion of children with untreated dentinal caries has improved from 2003, it remained high at 21% and 19% for 15-year-olds and 12-year-olds, respectively. These children are at high risk of pain and discomfort relating to their teeth. The 2013 survey also looked at the impact on daily life. On average, a fifth of 12- and 15-year-old children reported experiencing difficulty eating, and about half reported that their life had been affected by problems with their teeth or mouth within the previous 3 months (Steele et al. 2015). Caries prevalence declined in the later decades of the twentieth century. As it dropped, a concentration of the disease occurred, with a small percentage of the population experiencing most of the disease. Caries prevalence is greatest in the occlusal surfaces of the first permanent molars and buccal grooves of the lower first molars, and the prevalence in these sites has dropped by the smallest proportion. The least susceptible sites are the approximal surfaces of the incisors, so caries seen in these permanent teeth indicates more extensive disease (Sheiham and Sabbah 2010). The first permanent teeth erupt in the mouth at approximately 6 years of age, but may appear as early as 4 years of age. The eruption of the anterior teeth usually causes great excitement, as it is associated with ‘the fluttering of tooth fairy wings’. However, the eruption of the first permanent molars goes largely unnoticed until there is a problem.

Like other amino acids, the aromatic amino acids phenylalanine, tyrosine, and tryptophan are vitally important for protein synthesis in all organisms. However, while animals can synthesize tyrosine via oxidation of phenylalanine, they can synthesize neither phenylalanine itself nor tryptophan and so these essential amino acids must be obtained in the diet, usually from plant material. Though many other investigators made significant contributions in this area over the years, it was Bernhard Davis in the early 1950s whose use of mutant stains of Escherichia coli led to a full understanding of the so-called shikimic acid pathway that is used by plants and also by some microorganisms for the biosynthesis of these essential amino acids. The pathway is almost completely devoted to their synthesis for protein production in bacteria, while in plants the pathway extends their use to the construction of a wide array of secondary metabolites, many of which are valuable medicinal agents. These secondary metabolites range from simple and familiar compounds such as vanillin (vanilla flavor and fragrance) and eugenol (oil of clove, a useful dental anesthetic) to more complex structures such as pinoresinol, a common plant biochemical, and podophyllotoxin, a powerful cancer chemotherapy agent. Earlier in Chapter 3, we encountered two important intermediates, erythrose-4-phosphate and phosphoenolpyruvate (PEP), each of which was derived from a different pathway utilized in carbohydrate metabolism. Erythrose-4-P was an intermediate in one of the steps of the pentose phosphate pathway while hydrolysis of PEP to pyruvic acid was the final step in glycolysis. These two simple intermediates provide the seven carbon atoms required for construction of shikimic acid itself. The two are linked to one another via a sequence of enzyme-mediated aldol-type reactions, the first being a bimolecular reaction and the second an intramolecular variant that ultimately leads to a cyclic precursor of shikimic acid known as 3-dehydroquinic acid as shown in Fig. 6.3. Subsequent dehydration of 3-dehydroquinic acid leads to 3-dehydroshikimic acid which then leads directly to shikimic acid via NADPH reduction.

When temporally smoothed data are used for the period 1925 to 1985 there is a close inverse statistical relationship acting at an interdecadal timescale between the Pacific Northwest (PNW) air temperatures and Coho salmon catch off the coast of Washington and Oregon. This relationship is now well known, although not fully explained, but at the time of its discovery in 1994 it was part of advances being made by several research groups on interdecadal-scale climate/ecological changes in the PNW (Greenland 1995). The discovery and later, related findings may be usefully examined within the context of the framework questions of this book (see chapter 1) because it provides a very interesting example of climate variability and ecosystem response found, in part, by Long-Term Ecological Research (LTER) investigators. The logical progression for this chapter is first to review a little of the relationship between Coho salmon and climate and then to explain how a study at one LTER site led to a finding with regional implications. An update of the findings at interdecadal-scale climate/ecological changes in the PNW is then appropriate, followed by a discussion of the topic with the framework questions of this book. The PNW is defined, for the purposes of this chapter, as the area of Washington and Oregon west of the crest of the Cascade Range. The term decadal is used loosely in this chapter to refer to changes that focus on time periods of about 10 to 30 years in length. Salmon live part of their lives in terrestrial, freshwater environments and part in marine, saltwater environments. The salmon life history starts with fertilized eggs remaining in gravel in freshwater stream beds and hatching after 1–3 months. One to five months later, fry emerge in the spring or summer. Juvenile fish are in freshwater from a few days to 4 years, depending on species and locality. After the juveniles change to smolts, they can migrate to the ocean, usually in spring or early summer, often taking advantage of streamflows driven by snowmelt. The fish spend 1–4 years in the ocean and then return to their freshwater home stream to spawn and die. More specifically, the typical life cycle for Oregon Coho spans 3 years (18 months in freshwater and 18 months in the ocean).

One of the more powerful routes to enantiomerically-pure carbocycles is the desymmetrization of a prochiral ring. Karl Anker Jørgensen of Aarhus University has found (J. Am. Chem. Soc. 2007, 129, 441) that many cyclic β-ketoesters, including the vinylogous carbonate 1, can be homologated with 2 to the corresponding alkyne 3, in high ee. Sanzhong Luo of the Chinese Academy of Sciences, Beijing, and Jin-Pei Cheng, of the Chinese Academy of Sciences and Nankai University, have shown (J. Org. Chem. 2007, 72, 9350) that the catalyst 6 mediated the selective addition of 4-substituted cyclohexanones such as 4 to the nitroalkene 5, establishing three new stereogenic centers. Organocatalysts, alone or complexed with activating metals, have also been used to effect enantioselective ring construction. E. J. Corey of Harvard University has established (J. Am. Chem. Soc. 2007, 129, 12686) that the proline-derived complex 10 will mediate the 2 + 2 addition of a cyclic enol ether with an acrylate to give the cyclobutane 11. Further elaboration led to the cyclohexenone 12. Armando Córdova of Stockholm University has described (Tetrahedron Lett. 2007, 48, 5835) a novel route to cyclopentanones such as 16, via tandem conjugate addition/intramolecular alkylation. Professor Jørgensen has reported (Angew. Chem. Int. Ed . 2007, 46 , 9202) the double addition of 18 to the unsaturated aldehyde 17 to give 20. Earlier last year, Yujiro Hayashi of the Tokyo University of Science had shown (Angew. Chem. Int. Ed. 2007, 46, 4922) that the double addition of the inexpensive 21 to 5 could, depending on conditions, be directed selectively to 22, 23, or 24. As illustrated by the conversion of 8 to 13, organocatalysis can be used to effect the enantioselective construction of polycarbocyclic products. The initial ring prepared in enantiomerically-pure form by organocatalysis can also set the chirality of a polycyclic system. Professor Corey has reported (J. Am. Chem. Soc. 2007, 129, 10346) that Itsuno-Corey reduction of the prochiral diketone 25 led to the ketone 27. Cyclization followed by oxidation and reduction then delivered estrone methyl ether 28.

This task assesses the following clinical skills: … ● Patient safety ● Communication with patients and their relatives ● Information gathering ● Applied clinical knowledge … You are a ST4 doctor working in an infertility clinic. A couple who were referred to the clinic by their GP have returned for review. She has had oligomenorrhoea for the past year. She does not report headaches, visual disturbance, galactorrhoea or hyperandrogenism, she has been trying to conceive for two years. Her partner had an orchidopexy at the age of two. The assessor will ask you some questions and then give you the results of their investigations. You will be asked to explain the results and next steps to the patient. You have 10 minutes for this task (+ 2mins initial reading time). Please check that candidate and actor have read instructions. Ask the candidate what investigations they would like to organize for this patient and her partner. Give them the results of investigations (if asked for): Pregnancy test— ve LH 45, FSH 40, E2 120 (day two of cycle) PRL— 200 TSH— 1.2 Testosterone— 0.8 USS— NAD HSG— Patent tubes Rubella immune Chlamydia swabs— ve Smear— ve Semen analysis— 10m/ ml, 32% motility, 3% normal forms Ask them if they want to arrange any further investigations. Expect candidate to ask to repeat gonadotrophins more than a month after initial measurement in order to confirm the diagnosis of Premature Ovarian Insufficiency (POI). They should also repeat the semen analysis. Tell them that repeat gonadotrophins were again elevated— FSH 35, LH 20, E2 120. Repeat semen analysis was 15m/ ml, 34% motile, with 4% normal forms. Ask the candidate to explain these results to the patient and explain next steps, including further investigation and treatment options. They should then recommend that further investigations are arranged including karyotype, an auto-immune screen, lupus anticoagulant and vitamin B12 levels to try and identify a cause for the POI. Treatment options should include the role of hormone replacement therapy and oocyte donation with IVF. Observe consultation skills including the candidate’s ability to break bad news. Record your overall clinical impression of the candidate for each domain (i.e. pass, borderline, or fail).

Several independent series of observations demonstrate that there has been about 1°C of warming since the start of the industrial revolution. We discussed that there is some variability in solar output, and that these variations may be recognized in records of past climate, but also that solar variability can only account for warming by 0.1°C to an unlikely maximum of 0.35°C since the end of the Little Ice Age. Based on energy balance considerations, we have found that our emissions of external carbon are the main culprit. In response to this disturbance of the energy balance, the climate simply has to change toward a warmer Pliocene- like state, even if we could manage to stabilize CO2 at its current level of about 400 ppm. From discussion of several slowly adjusting processes within the climate system, we now understand that it will take, from the beginning, several centuries to approximate the full Pliocene- like warming. But we are almost two centuries down the road, and warming to date already amounts to about 1°C. The slow components in the climate system will cause continuing warming by another 1°C or so. In other words, we are already committed to further warming, even if we managed to make the massive jump to a zero- emissions society from today and thus stabilize CO2 levels. The urgency of slashing back the current level of annual emissions (10 GtC) cannot be overstated. Every year of inaction brings us closer to the inevitability of a future climate that will exceed even the warm Pliocene state, with global temperatures at least 2 or 3°C higher than the pre- industrial level. If we allow ourselves to reach the Paris Climate Conference’s agreed maximum of 2°C warming by the year 2100, then the further commitment over coming centuries would take us toward 4°C, even if we achieved zero emissions by 2100. That is considerably warmer than during the Pliocene. We have seen that the consequences are grave. Progression toward a Pliocene- like climate state will be accompanied by continued migration of global and regional climate zones and by intensification of the evaporation and precipitation cycle, placing many areas at risk of increasing extremes, including aridity, flooding, and lethal heat.

Externally fired gas turbine (EFGT) cycles in combination with a biomass-fueled, atmospheric circulating fluidized bed (CFB) furnace are investigated for small scale production of power and district heat. Both closed and open gas turbine cycle configurations are considered. The thermodynamic performance analysis includes an evaluation of cycle-to-furnace heat matching and cycle-side pressure loss considerations. An economic analysis is presented for the various EFGT configurations, and comparisons are made with existing and emerging alternatives for small-scale biomass cogeneration. Simulation results show that thermodynamic performance varies between the different configurations and working fluids, with electric efficiencies in the range of 31–38% (LHV) and total efficiencies of 86–106% (LHV). An economic evaluation for an 8 MWf plant shows that the specific capital cost is about 3200–3900 $/kWe for a first commercial plant. The turbomachinery and the CFB furnace dominate the total plant cost, with each contributing about 1/3 of the total installed equipment cost. The cost of electricity, COE, is estimated to be 73–84 $/MWhe for 4 000 full load hours per year in a cogeneration application.

This extended abstract describes a sonification that was commissioned by a biologist/animal ecologist. The sonification was created with the software synthesis program SuperCollider [1]. The motivation for creating it was to pursue additional levels of engagement and immersion by supplementing the effects of visual plots, as well as to create an informative rendering of a multivariate dataset. The goal is for audiences, in particular students and laypeople, to readily understand (and hopefully find compelling) the phenomena being described. The approach is parameterbased, creating “sonic scatter plots” [2] in the same manner as work described in earlier publications [3], [4]. The work described here is a current experimental project that takes a sonic approach to describing the interactions of plant phenology and animal migrations in Greenland. This area is seen as a predictor of how climate change may affect areas farther south. There is concern about the synchronicity of annual caribou migrations with the appearance of plant food sources, as warmer temperatures may cause plants to bloom earlier and in advance of the caribou arrival at their calving grounds; depleted food availability at calving time can lead to lower populations of caribou. Parts of this sonification will be applied to a multi-year professional development workshop for middle and high school science teachers. It is hoped that sonifications of plant observations made by teachers and students will enhance student engagement, and possibly lead to greater degrees of understanding of phenology patterns.

In 2006, the ports of Long Beach and Los Angeles adopted the final San Pedro Bay Ports Clean Air Action Plan (CAAP), initiating a broad range of programs intended to improve the air quality of the port and rail yard communities in the South Coast Air Basin. As a result, the Technology Advancement Program (TAP) was formed to identify, evaluate, verify and accelerate the commercial availability of new emissions reduction technologies for emissions sources associated with port operations, [1]. Container drayage truck fleets, an essential part of the port operations, were identified as the second largest source of NOx and the fourth largest source of diesel PM emissions in the ports’ respective 2010 emissions inventories [2, 3]. In response, TAP began to characterize drayage truck operations in order to provide drayage truck equipment manufacturers with a more complete understanding of typical drayage duty cycles, which is necessary to develop emissions reduction technologies targeted at the drayage market. As part of the broader TAP program, the Ports jointly commissioned TIAX LLC to develop a series of drayage truck chassis dynamometer test-cycles. These cycles were based on the cargo transport distance, using vehicle operational data collected on a second-by-second basis from numerous Class 8 truck trips over a period of two weeks, while performing various modes of typical drayage-related activities. Distinct modes of operation were identified; these modes include creep, low-speed transient, high-speed transient and high-speed cruise. After the modes were identified, they were assembled in order to represent typical drayage operation, namely, near-dock operation, local operation and regional operation, based on cargo transport distances [4]. The drayage duty-cycles, thus developed, were evaluated on a chassis dynamometer at West Virginia University (WVU) using a class 8 tractor powered by a Mack MP8-445C, 13 liter 445 hp, and Model Year (MY) 2011 engine. The test vehicle is equipped with a state-of-the-art emissions control system meeting 2010 emissions regulations for on-road applications. Although drayage trucks in the San Pedro Bay Ports do not have to comply with the 2010 heavy-duty emissions standards until 2023, more than 1,000 trucks already meet that standard and are equipped with diesel particulate filter (DPF) and selective catalytic reduction (SCR) technology as used in the test vehicle. An overview of the cycle evaluation work, along with comparative results of emissions between integrated drayage operations, wherein drayage cycles are run as a series of shorter tests called drayage activities, and single continuous drayage operation cycles will be presented herein. Results show that emissions from integrated drayage operations are significantly higher than those measured over single continuous drayage operation, approximately 14% to 28% for distance-specific NOx emissions. Furthermore, a similar trend was also observed in PM emissions, but was difficult to draw a definite conclusion since PM emissions were highly variable and near detection limits in the presence of DPF. Therefore, unrepresentative grouping of cycle activity could lead to over-estimation of emissions inventory for a fleet of drayage vehicles powered by 2010 compliant on-road engines.

An engineering study of the main steam line pressure tap cracking was performed. The failure mechanism was thermal fatigue and the circumferential cracks initiate at the pipe penetration on the inside surface of the pipe. Based on the results, a parametric fitness for service study was performed to develop a flaw tolerance graph to be used for the evaluation and disposition of detected defects. The parameters are pipe diameter, penetration diameter, and inspection interval. The objective is to determine the value of the current crack size when weld repair is needed. The fatigue crack growth calculations used the NASGRO computer program. The crack geometries were a single corner crack from a hole in a plate and a corner crack from a hole in a plate with two cracks. The analysis used the properties for Grade 22 plate material given in the program and applied a correction factor (69 cycles for Grade 22 at room temperature equals 1 fatigue cycle with hold time of 12 hours for P11) to account for the pipe material of P11, 1-1/4Cr-1/2Mo and the nominal operating temperature of 482°C. There were approximately 40 cold starts and 210 hot starts per year for the unit. The magnitude of the remote stress depended on the temperature range for the hot and cold starts. The applied stress consisted of tension and bending stresses and was estimated by the observed failure life of approximately 20 years for the 3/4 penetration in the pipe size 18 pipe.

Offshore platform resistance to cyclic storm actions is addressed. In order to achieve the best economy of the structure especially when assessing existing structures, the ultimate capacity of the structure is utilized. This means that parts of the structure may be loaded into the non-linear range and consequently the load-carrying resistance of the structure against future load cycles may be reduced. In such cases it is required to carry out a check of the cyclic capacity of the structure. Such checks are required in the ISO 19902 code for Fixed Steel Offshore Structures. The paper presents a proposal for how a load history for cyclic checks can be established. The method is in line with what is included in the NORSOK N-006 standard on “Assessment of structural integrity for existing load-bearing structures”. The load-history for the waves in the design storm may be expressed as ratio of the dimensioning wave. The ratio will be different for check of failure modes where the entire storm will be relevant such as crack growth, compared to failure modes like buckling where only the remaining waves after the dimensioning wave need to be accounted for. Using simple order statistics and simulation, the statistics for the ith (Hi), i = 1, 2, 3, 4 etc. highest wave in the storm is studied in some detail, assuming that the maximum wave (H1) is equal to an extreme wave obtained by a code requirement. Environmental contours for the pair (H1,H2) are established by Inverse FORM for design conditions. Further, the long term statistics for load effects that are expressed as a function of H1, .., H4, i.e. L = f(H1, .., H4), are determined. The R-year value LR for the load effect L is determined by structural reliability techniques, and the most probable combination (design point) (H1*, .., H4*) for L = LR is determined. The design point values Hi*, as well as the design point value for the significant wave height, are determined for different load effects, and their characteristics for different types of load effects are discussed. The paper gives advice also on how to establish the magnitude for the remaining waves in the storm.

Abstract The Boiling Water Reactor (BWR) Mark I (Mk I) Containment Program was implemented by the Owner’s Group circa 1970 to mitigate the effects of small, intermediate and design bases, Loss of Coolant Accident (LOCA), pipe break accidents on the torus, supports, internal structures and attached piping [1 & 2]. One of the significant mitigation attributes implemented during the Mk I Program is Normal Operation (NO) with a drywell-to-wetwell Differential Pressure (dP) maintained by the plant Nitrogen Make-up System used to inert the Primary Containment (PC) [3]. The differential pressure served to reduce the downcomer water leg in the vent system resulting in significantly reduced vent system thrust and pool swell loads. The vent system is designed to transport the mixture of drywell atmosphere, steam, and water forced from the drywell by the increasing pressure post-accident, quenching it in the pool of water maintained in the suppression chamber (torus). Based on plant experience, to sustain PC dP requires frequent venting of the Torus or nitrogen make-up to the drywell requiring Standby Gas System operation and cycling of PC vent and purge valves which places additional burden on the charcoal filters. The venting also places burden on Control Room Operators to perform the required actions and maintain Technical Specification (TS) limits. Elimination of the dP benefits plant operation by minimizing cycling of PC Isolation Valves, reduction of burden on Control Room operators due to the wider pressure control envelop, reduction in Standby Gas System cycles extending charcoal filter life and a reduction of the nitrogen make-up [4]. Overall, the Utility estimates that elimination of the dP will provide an estimated cost savings of $0.5 M per year.

Ethylene plant is the critical plant in petrochemical industry, the output of its major product - ethylene directly reflects the development situation of a country’s petrochemical industry, therefore, the long-cycle safe running of the ethylene plant is of important significance. At present, the operation cycle of ethylene plants in developed countries is generally 4∼6 years, whereas that in China is mostly 3 years, which seriously restricts the production capacity, cost and international competitive power of Chinese ethylene production enterprises. With a great number of new or expansion projects of 1,000,000 tons/year ethylene plants put into production successively in China, it is extremely urgent to guarantee long-cycle running of ethylene plants. Starting from 2003, we initially adopted risk-based inspection (RBI) technology in Chinese ethylene plants, and achieved the objective of extending the inspection interval of ethylene plants from the original 3 years to 6 years in combination with technical means like online inspection etc. Up to the present, we have completed RBI of 13 ethylene plants, and the running cycle of most of them has been extended. In this paper the application situation of RBI technology in ethylene plants is presented, by means of RBI, major factors that influence long-cycle safe running of ethylene plants are identified effectively, and feasible risk reduction measures have been developed, which provide reliable assurance for long-cycle safe running of the ethylene plants.

Over the past 5–10 years, interest has increased significantly in CO2 free power generation cycles. This study focuses on precombustion decarbonization cycles that reform syngas, separating the CO2 using a membrane, and then burning hydrogen-rich fuel in a gas turbine. The syngas reforming section is comprised of 1) Auto-thermal reformer (ATR) used for syngas production 2) water gas shift reactor (WGSR) to shift CO into CO2 3) CO2 -separation membrane and 4) combustion with hydrogen rich fuel. Overall performance shows an efficiency loss of 8.4% and 10.6% compared to the baseline cycle for the high and low temperature CO2 membrane cycles examined. The operating temperatures of the membranes are limited by the exothermic CO shift reaction favoring lower temperatures. Furthermore, a chemical exergy analysis of the reformers in the decarbonization system is undertaken to understand the impact of fuel reforming.

New structural materials that are light and durable are anticipated to reduce the running and maintenance costs of structures exposed to harsh marine environments, such as offshore oil production facilities, thereby reducing their life-cycle cost. This study aims to investigate the applicability of new materials to marine structures, focusing on their durability. To this end, a 5-year exposure test has been conducted from 1999 on 3 types of specimens (for corrosion observation, tension testing, and joint strength testing) made of 21 selected materials (6 nonferrous metals, 8 steels, 4 composite materials, and 3 rope materials). The specimens are exposed at 3 sites: Okinotori-shima and Miyako-jima, corrosive environments with high temperature and humidity, and a thermo-hygrostatic room in a laboratory. In 2003, the fourth year of the ongoing exposure testing, the results of the observation and experiments of specimens recovered in 2002 after exposure for 3 years are subjected to analysis. The authors have already reported the detailed plan of the exposure test, initial performance of the specimens, and results of investigation on specimens exposed for 1 year. This paper reports on the results of appearance observation of specimens at Okinotori-shima and Miyako-jima carried out mostly in 2001, as well as the findings from observation and experiments on specimens exposed for 2 years at Miyako-jima. The state of corrosion at each site was grasped during the appearance observation. Observation and tension tests on jointed and unjointed specimens at Miyako-jima also revealed the state of corrosion of each material during the 2nd year of exposure.

Abstract Gas production from unconventional shale reservoirs is known for rapid declines. Intermittent shut-in production constitutes a technique typically applied to low-production wells during late life stages to maintain economic rates. This technique involves a cyclic process of shutting in the well temporarily to allow it to build up pressure and subsequently switching the well to production. Operators often manage hundreds of wells on intermittent shut-in production; these wells, however, incur different shut-in and production cycle times, thus requiring a complicated management approach. Because every well has a unique production behavior and reservoir characteristics, searching for optimum operational conditions individually is not only technically challenging, but also operationally time-consuming and labor- intensive. Our goal was to use active learning analytic, a type of machine learning deployed on an edge computing platform, to autonomously control and optimize these unconventional gas wells. The field trial results show increased production, reduced liquid loading, decreased manual intervention, and reduced carbon footprint. Our solution utilizes an edge computing platform to deploy the analytic on the wellhead without requiring a stable internet connection. A computing device at the edge connects to controllers on site, processes data, sets system control parameters, and enables automation for operations deploying an optimization algorithm. Active learning algorithms are valuable for use in the optimization of systems that are not mathematically definable. These algorithms are also proven to learn the relationship between the inputs and outputs and use prior knowledge to intelligently search for the optimum settings within the defined operating limits. The low latency of edge computing allows for high-frequency data collection in seconds and a rapid control of the wells. The edge device continuously monitors production and initiates re- optimization as needed when operational conditions change. We developed an analytic that autonomously controls the intermittent production technique where a well is shut-in based on a specified minimum gas production rate and opened when the pressure builds up to the specified target during the shut-in period. The analytic actively learns and measures the ways in which the specified parameters improve production rates. Additionally, the analytic continuously monitors production data and identifies any well liquid loading events. When liquid loading occurs in the wellbore as observed from the production pattern, the analytic automatically shuts in the well to build up pressure and minimizes additional liquid formation. In the field trial, we deployed the edge analytic to monitor gas production and the specified well shut-in and open conditions for 10 different wells in the Haynesville Shale Play. Analyzing each well in the context of approximately 30 intermittent production cycles (shut- in/open), the analytic successfully mapped the surface response, identified the optimal setting for well shut-in/open conditions, and continuously updated the surface response. Overall, the analytic improved production by 4% and reduced the liquid loading occurrences and manual well unloading events by 94%, resulting in an average reduction of approximately 600 tons of CO2 equivalent per well per year. In summary the active learning analytic was developed and deployed on an edge computing platform to 1) optimize intermittent shut-in by searching for the optimum settings that yield the most gas production; 2) automate the optimization process; and 3) monitor the liquid formation for potential loading events. In this paper, we present a use case for an algorithm adapted for the optimization of a dynamic system such as hydrocarbon production from a well.

20 years ago a concept of “Green Chemistry” was formulated by Paul Anastas and John Warner, aiming at an ambitious agenda to “green” chemical products and processes. Today the concept, laid down in a set of 12 principles, has found support in various arenas. This diffusion was supported by enhancements of the legislative framework; not only in the European Union. Nevertheless industry actors – whilst generally supporting the idea – still see “cost and perception remain barriers to green chemistry uptake”. Thus, the questions arise how additional incentives as well as measures to address the barriers and impediments can be provided. An analysis addressing these questions has to take into account the institutional context for the relevant actors involved in the issue. And it has to reflect the problem perception of the different stakeholders. The supply chain into which the chemicals are distributed are of pivotal importance since they create the demand pull for chemicals designed in accordance with the “Green Chemistry Principles”. Consequently, the scope of this study includes all stages in a chemical’s life-cycle, including the process of designing and producing the final products to which chemical substances contribute. For each stage the most relevant legislative acts, together establishing the regulatory framework of the “chemicals policy” in the EU are analysed. In a nutshell the main elements of the study can be summarized as follows: Green Chemistry (GC) is the utilisation of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products. Besides, reaction efficiency, including energy efficiency, and the use of renewable resources are other motives of Green Chemistry. Putting the GC concept in a broader market context, however, it can only prevail if in the perception of the relevant actors it is linked to tangible business cases. Therefore, the study analyses the product context in which chemistry is to be applied, as well as the substance’s entire life-cycle – in other words, the six stages in product innovation processes): 1. Substance design, 2. Production process, 3. Interaction in the supply chain, 4. Product design, 5. Use phase and 6. After use phase of the product (towards a “circular economy”). The report presents an overview to what extent the existing framework, i.e. legislation and the wider institutional context along the six stages, is setting incentives for actors to adequately address problematic substances and their potential impacts, including the learning processes intended to invoke creativity of various actors to solve challenges posed by these substances. In this respect, measured against the GC and Learning Process assessment criteria, the study identified shortcomings (“delta”) at each stage of product innovation. Some criteria are covered by the regulatory framework and to a relevant extent implemented by the actors. With respect to those criteria, there is thus no priority need for further action. Other criteria are only to a certain degree covered by the regulatory framework, due to various and often interlinked reasons. For those criteria, entry points for options to strengthen or further nuance coverage of the respective principle already exist. Most relevant are the deltas with regard to those instruments that influence the design phase; both for the chemical substance as such and for the end-product containing the substance. Due to the multi-tier supply chains, provisions fostering information, communication and cooperation of the various actors are crucial to underpin the learning processes towards the GCP. The policy options aim to tackle these shortcomings in the context of the respective stage in order to support those actors who are willing to change their attitude and their business decisions towards GC. The findings are in general coherence with the strategies to foster GC identified by the Green Chemistry & Commerce Council.

1.1 Macroeconomic summary Economic recovery has consistently outperformed the technical staff’s expectations following a steep decline in activity in the second quarter of 2020. At the same time, total and core inflation rates have fallen and remain at low levels, suggesting that a significant element of the reactivation of Colombia’s economy has been related to recovery in potential GDP. This would support the technical staff’s diagnosis of weak aggregate demand and ample excess capacity. The most recently available data on 2020 growth suggests a contraction in economic activity of 6.8%, lower than estimates from January’s Monetary Policy Report (-7.2%). High-frequency indicators suggest that economic performance was significantly more dynamic than expected in January, despite mobility restrictions and quarantine measures. This has also come amid declines in total and core inflation, the latter of which was below January projections if controlling for certain relative price changes. This suggests that the unexpected strength of recent growth contains elements of demand, and that excess capacity, while significant, could be lower than previously estimated. Nevertheless, uncertainty over the measurement of excess capacity continues to be unusually high and marked both by variations in the way different economic sectors and spending components have been affected by the pandemic, and by uneven price behavior. The size of excess capacity, and in particular the evolution of the pandemic in forthcoming quarters, constitute substantial risks to the macroeconomic forecast presented in this report. Despite the unexpected strength of the recovery, the technical staff continues to project ample excess capacity that is expected to remain on the forecast horizon, alongside core inflation that will likely remain below the target. Domestic demand remains below 2019 levels amid unusually significant uncertainty over the size of excess capacity in the economy. High national unemployment (14.6% for February 2021) reflects a loose labor market, while observed total and core inflation continue to be below 2%. Inflationary pressures from the exchange rate are expected to continue to be low, with relatively little pass-through on inflation. This would be compatible with a negative output gap. Excess productive capacity and the expectation of core inflation below the 3% target on the forecast horizon provide a basis for an expansive monetary policy posture. The technical staff’s assessment of certain shocks and their expected effects on the economy, as well as the presence of several sources of uncertainty and related assumptions about their potential macroeconomic impacts, remain a feature of this report. The coronavirus pandemic, in particular, continues to affect the public health environment, and the reopening of Colombia’s economy remains incomplete. The technical staff’s assessment is that the COVID-19 shock has affected both aggregate demand and supply, but that the impact on demand has been deeper and more persistent. Given this persistence, the central forecast accounts for a gradual tightening of the output gap in the absence of new waves of contagion, and as vaccination campaigns progress. The central forecast continues to include an expected increase of total and core inflation rates in the second quarter of 2021, alongside the lapse of the temporary price relief measures put in place in 2020. Additional COVID-19 outbreaks (of uncertain duration and intensity) represent a significant risk factor that could affect these projections. Additionally, the forecast continues to include an upward trend in sovereign risk premiums, reflected by higher levels of public debt that in the wake of the pandemic are likely to persist on the forecast horizon, even in the context of a fiscal adjustment. At the same time, the projection accounts for the shortterm effects on private domestic demand from a fiscal adjustment along the lines of the one currently being proposed by the national government. This would be compatible with a gradual recovery of private domestic demand in 2022. The size and characteristics of the fiscal adjustment that is ultimately implemented, as well as the corresponding market response, represent another source of forecast uncertainty. Newly available information offers evidence of the potential for significant changes to the macroeconomic scenario, though without altering the general diagnosis described above. The most recent data on inflation, growth, fiscal policy, and international financial conditions suggests a more dynamic economy than previously expected. However, a third wave of the pandemic has delayed the re-opening of Colombia’s economy and brought with it a deceleration in economic activity. Detailed descriptions of these considerations and subsequent changes to the macroeconomic forecast are presented below. The expected annual decline in GDP (-0.3%) in the first quarter of 2021 appears to have been less pronounced than projected in January (-4.8%). Partial closures in January to address a second wave of COVID-19 appear to have had a less significant negative impact on the economy than previously estimated. This is reflected in figures related to mobility, energy demand, industry and retail sales, foreign trade, commercial transactions from selected banks, and the national statistics agency’s (DANE) economic tracking indicator (ISE). Output is now expected to have declined annually in the first quarter by 0.3%. Private consumption likely continued to recover, registering levels somewhat above those from the previous year, while public consumption likely increased significantly. While a recovery in investment in both housing and in other buildings and structures is expected, overall investment levels in this case likely continued to be low, and gross fixed capital formation is expected to continue to show significant annual declines. Imports likely recovered to again outpace exports, though both are expected to register significant annual declines. Economic activity that outpaced projections, an increase in oil prices and other export products, and an expected increase in public spending this year account for the upward revision to the 2021 growth forecast (from 4.6% with a range between 2% and 6% in January, to 6.0% with a range between 3% and 7% in April). As a result, the output gap is expected to be smaller and to tighten more rapidly than projected in the previous report, though it is still expected to remain in negative territory on the forecast horizon. Wide forecast intervals reflect the fact that the future evolution of the COVID-19 pandemic remains a significant source of uncertainty on these projections. The delay in the recovery of economic activity as a result of the resurgence of COVID-19 in the first quarter appears to have been less significant than projected in the January report. The central forecast scenario expects this improved performance to continue in 2021 alongside increased consumer and business confidence. Low real interest rates and an active credit supply would also support this dynamic, and the overall conditions would be expected to spur a recovery in consumption and investment. Increased growth in public spending and public works based on the national government’s spending plan (Plan Financiero del Gobierno) are other factors to consider. Additionally, an expected recovery in global demand and higher projected prices for oil and coffee would further contribute to improved external revenues and would favor investment, in particular in the oil sector. Given the above, the technical staff’s 2021 growth forecast has been revised upward from 4.6% in January (range from 2% to 6%) to 6.0% in April (range from 3% to 7%). These projections account for the potential for the third wave of COVID-19 to have a larger and more persistent effect on the economy than the previous wave, while also supposing that there will not be any additional significant waves of the pandemic and that mobility restrictions will be relaxed as a result. Economic growth in 2022 is expected to be 3%, with a range between 1% and 5%. This figure would be lower than projected in the January report (3.6% with a range between 2% and 6%), due to a higher base of comparison given the upward revision to expected GDP in 2021. This forecast also takes into account the likely effects on private demand of a fiscal adjustment of the size currently being proposed by the national government, and which would come into effect in 2022. Excess in productive capacity is now expected to be lower than estimated in January but continues to be significant and affected by high levels of uncertainty, as reflected in the wide forecast intervals. The possibility of new waves of the virus (of uncertain intensity and duration) represents a significant downward risk to projected GDP growth, and is signaled by the lower limits of the ranges provided in this report. Inflation (1.51%) and inflation excluding food and regulated items (0.94%) declined in March compared to December, continuing below the 3% target. The decline in inflation in this period was below projections, explained in large part by unanticipated increases in the costs of certain foods (3.92%) and regulated items (1.52%). An increase in international food and shipping prices, increased foreign demand for beef, and specific upward pressures on perishable food supplies appear to explain a lower-than-expected deceleration in the consumer price index (CPI) for foods. An unexpected increase in regulated items prices came amid unanticipated increases in international fuel prices, on some utilities rates, and for regulated education prices. The decline in annual inflation excluding food and regulated items between December and March was in line with projections from January, though this included downward pressure from a significant reduction in telecommunications rates due to the imminent entry of a new operator. When controlling for the effects of this relative price change, inflation excluding food and regulated items exceeds levels forecast in the previous report. Within this indicator of core inflation, the CPI for goods (1.05%) accelerated due to a reversion of the effects of the VAT-free day in November, which was largely accounted for in February, and possibly by the transmission of a recent depreciation of the peso on domestic prices for certain items (electric and household appliances). For their part, services prices decelerated and showed the lowest rate of annual growth (0.89%) among the large consumer baskets in the CPI. Within the services basket, the annual change in rental prices continued to decline, while those services that continue to experience the most significant restrictions on returning to normal operations (tourism, cinemas, nightlife, etc.) continued to register significant price declines. As previously mentioned, telephone rates also fell significantly due to increased competition in the market. Total inflation is expected to continue to be affected by ample excesses in productive capacity for the remainder of 2021 and 2022, though less so than projected in January. As a result, convergence to the inflation target is now expected to be somewhat faster than estimated in the previous report, assuming the absence of significant additional outbreaks of COVID-19. The technical staff’s year-end inflation projections for 2021 and 2022 have increased, suggesting figures around 3% due largely to variation in food and regulated items prices. The projection for inflation excluding food and regulated items also increased, but remains below 3%. Price relief measures on indirect taxes implemented in 2020 are expected to lapse in the second quarter of 2021, generating a one-off effect on prices and temporarily affecting inflation excluding food and regulated items. However, indexation to low levels of past inflation, weak demand, and ample excess productive capacity are expected to keep core inflation below the target, near 2.3% at the end of 2021 (previously 2.1%). The reversion in 2021 of the effects of some price relief measures on utility rates from 2020 should lead to an increase in the CPI for regulated items in the second half of this year. Annual price changes are now expected to be higher than estimated in the January report due to an increased expected path for fuel prices and unanticipated increases in regulated education prices. The projection for the CPI for foods has increased compared to the previous report, taking into account certain factors that were not anticipated in January (a less favorable agricultural cycle, increased pressure from international prices, and transport costs). Given the above, year-end annual inflation for 2021 and 2022 is now expected to be 3% and 2.8%, respectively, which would be above projections from January (2.3% and 2,7%). For its part, expected inflation based on analyst surveys suggests year-end inflation in 2021 and 2022 of 2.8% and 3.1%, respectively. There remains significant uncertainty surrounding the inflation forecasts included in this report due to several factors: 1) the evolution of the pandemic; 2) the difficulty in evaluating the size and persistence of excess productive capacity; 3) the timing and manner in which price relief measures will lapse; and 4) the future behavior of food prices. Projected 2021 growth in foreign demand (4.4% to 5.2%) and the supposed average oil price (USD 53 to USD 61 per Brent benchmark barrel) were both revised upward. An increase in long-term international interest rates has been reflected in a depreciation of the peso and could result in relatively tighter external financial conditions for emerging market economies, including Colombia. Average growth among Colombia’s trade partners was greater than expected in the fourth quarter of 2020. This, together with a sizable fiscal stimulus approved in the United States and the onset of a massive global vaccination campaign, largely explains the projected increase in foreign demand growth in 2021. The resilience of the goods market in the face of global crisis and an expected normalization in international trade are additional factors. These considerations and the expected continuation of a gradual reduction of mobility restrictions abroad suggest that Colombia’s trade partners could grow on average by 5.2% in 2021 and around 3.4% in 2022. The improved prospects for global economic growth have led to an increase in current and expected oil prices. Production interruptions due to a heavy winter, reduced inventories, and increased supply restrictions instituted by producing countries have also contributed to the increase. Meanwhile, market forecasts and recent Federal Reserve pronouncements suggest that the benchmark interest rate in the U.S. will remain stable for the next two years. Nevertheless, a significant increase in public spending in the country has fostered expectations for greater growth and inflation, as well as increased uncertainty over the moment in which a normalization of monetary policy might begin. This has been reflected in an increase in long-term interest rates. In this context, emerging market economies in the region, including Colombia, have registered increases in sovereign risk premiums and long-term domestic interest rates, and a depreciation of local currencies against the dollar. Recent outbreaks of COVID-19 in several of these economies; limits on vaccine supply and the slow pace of immunization campaigns in some countries; a significant increase in public debt; and tensions between the United States and China, among other factors, all add to a high level of uncertainty surrounding interest rate spreads, external financing conditions, and the future performance of risk premiums. The impact that this environment could have on the exchange rate and on domestic financing conditions represent risks to the macroeconomic and monetary policy forecasts. Domestic financial conditions continue to favor recovery in economic activity. The transmission of reductions to the policy interest rate on credit rates has been significant. The banking portfolio continues to recover amid circumstances that have affected both the supply and demand for loans, and in which some credit risks have materialized. Preferential and ordinary commercial interest rates have fallen to a similar degree as the benchmark interest rate. As is generally the case, this transmission has come at a slower pace for consumer credit rates, and has been further delayed in the case of mortgage rates. Commercial credit levels stabilized above pre-pandemic levels in March, following an increase resulting from significant liquidity requirements for businesses in the second quarter of 2020. The consumer credit portfolio continued to recover and has now surpassed February 2020 levels, though overall growth in the portfolio remains low. At the same time, portfolio projections and default indicators have increased, and credit establishment earnings have come down. Despite this, credit disbursements continue to recover and solvency indicators remain well above regulatory minimums. 1.2 Monetary policy decision In its meetings in March and April the BDBR left the benchmark interest rate unchanged at 1.75%.