Journal articles on the topic 'Intra-horizon risk'

We propose a consistent and computationally efficient 2-step methodology for the estimation of multidimensional non-Gaussian asset models built using Lévy processes. The proposed framework allows for dependence between assets and different tail behaviors and jump structures for each asset. Our procedure can be applied to portfolios with a large number of assets because it is immune to estimation dimensionality problems. Simulations show good finite sample properties and significant efficiency gains. This method is especially relevant for risk management purposes such as, for example, the computation of portfolio Value at Risk and intra-horizon Value at Risk, as we show in detail in an empirical illustration.

Purpose This article aims to analyze the performance and risk of landmark building in the housing sector and to evaluate their usefulness for a diversification strategy. Design/methodology/approach After comparing summary statistics on the performance of landmark building with respect to other types of housing investments, the article evaluates their usefulness for a diversification strategy. The role of landmark buildings is studied using the modern portfolio theory and evaluating the role of this type of asset in the optimal asset allocation. The analysis is performed considering both the risk/return trade-off in a one-year and a multiple-year time horizon. Findings The results show that a landmark building can be a good investment opportunity, especially for high-risk/return investors. A not perfect correlation of the returns of this asset class with other types of housing investments implies the existence of a minimum investment in this asset class for almost all portfolios on the efficient frontier. Results are robust with respect to the length of the investment time horizon. Originality/value The article presents a unique analysis of intra-housing market diversification opportunities focusing on the role of landmark building in the portfolio construction. Empirical evidence supports the hypothesis that real estate investors can take advantage of investing in landmark buildings in the residential sector as well because there are no reasons to limit such investments to trophy buildings in the office and commercial sectors.

Mackerel, the third largest oil field in the Gippsland Basin, is a mature field with over 80 per cent of reserves produced from 18 original development wells.The initial Mackerel development was based on a fairly simplistic reservoir model incorporating the results of the four exploration wells. The net to gross was anticipated at 90 per cent throughout the reservoir and no significant permeability barriers were expected. After 10 years of production a review of field performance indicated the reservoir was not as homogenous as first anticipated.Redevelopment of the Mackerel Field began in 1990 following the acquisition of the first of two high resolution 3D surveys and culminated in the drilling of 18 additional wells from the Mackerel platform during 1993 and 1994. It was these 3D surveys which changed the entire reservoir model of Mackerel to one of a far more compartmentalised nature.Seismic attribute analysis, when calibrated to 2D forward modelling was used to predict intra-reser- voir seals and the distribution of poorer quality reservoir; both not previously recognised over the field. The truncation points of the intra-reservoir seals against the main field-wide trapping unconformity were accurately mapped using seismic attributes and image enhancement techniques such as ER Mapper. Previously undetectable fault extensions, with throw around 10 m, can act as partial flow barriers and were recognised for the first time via 'sun-angle illumination' of azimuth maps. This allowed optimum well placement and helped explain historical field performance. Horizon slicing techniques and the calibration of volume attributes were used to establish depositional environments and seal capacity of the predicted intra-reservoir seals.The drilling results have shown that over the production life of the Mackerel Field the reservoir consists of a number of drainage compartments, each separated by seismically resolvable intra-res- ervoir seals.The redevelopment of the Mackerel field increased production rate by 18 thousand barrels per day (kBD) in 1993, and proved additional capture reserves of which approximately 40 percent can be directly attributed to the 3D seismic data and the applied interpretation techniques.

This study examines the dynamic nature of return spillover across Bitcoins indices and foreign exchange pairs denominated in 6 major trading currencies. The findings of spillover index, Spillover Asymmetry Measure (SAM) and frequency connectedness methodologies indicate that return spillover across Bitcoin markets and foreign exchange pairs dominated in six major trading currencies is very low. The intra-market return spillover for the Bitcoin markets and foreign exchange pairs is found to be significant. Presence of asymmetry in the return spillover is also found. Evidence indicates that return spillover are dominated in short horizon, with significant spillover occurring within 4 days of an event. The low integration of Bitcoin markets with the foreign exchange markets provide significant implication for portfolio diversification and risk minimization.

An epidemiological model, which describes the transmission dynamics of SARS-CoV-2 under specific consideration of the incubation period including the population with subclinical infections and being infective is presented. The COVID-19 epidemic in Greece was explored through a Monte Carlo uncertainty analysis framework, and the optimal values for the parameters that determined the transmission dynamics could be obtained before, during, and after the interventions to control the epidemic. The dynamic change of the fraction of asymptomatic individuals was shown. The analysis of the modelling results at the intra-annual climatic scale allowed for in depth investigation of the transmission dynamics of SARS-CoV-2 and the significance and relative importance of the model parameters. Moreover, the analysis at this scale incorporated the exploration of the forecast horizon and its variability. Three discrete peaks were found in the transmission rates throughout the investigated period (15 February–15 December 2020). Two of them corresponded to the timing of the spring and autumn epidemic waves while the third one occurred in mid-summer, implying that relaxation of social distancing and increased mobility may have a strong effect on rekindling the epidemic dynamics offsetting positive effects from factors such as decreased household crowding and increased environmental ultraviolet radiation. In addition, the epidemiological state was found to constitute a significant indicator of the forecast reliability horizon, spanning from as low as few days to more than four weeks. Embedding the model in an ensemble framework may extend the predictability horizon. Therefore, it may contribute to the accuracy of health risk assessment and inform public health decision making of more efficient control measures.

Recent studies undertaken by Hydro-Québec evaluate three aspects of the integration of wind generation on their system reliability/security. In an operations setting, the impacts on intra-hourly operating reserves and on extra-hourly balancing reserves are examined. On an operations planning horizon, the wind power capacity credit is evaluated for winter peak loading conditions, when very cold temperatures risk disabling part of the wind generation. Depending on the study, various mathematical tools were used to generate the statistical characteristics of the load and anticipated wind generation: time-series analysis, wind simulation at new/future wind plant sites, power system simulation and a posteriori determination of forecast errors. However, in each case the measure used to quantify the impact of wind generation has been related to the change in the variance of the total system uncertainty as a result of the addition of wind power generation.

BackgroundHydroxychloroquine (HCQ) is a key treatment for patients with lupus, but the major long-term toxicity is HCQ retinopathy. A large cross-sectional study found a prevalence of HCQ retinopathy of 7.5% overall and 5 times higher odds associated with HCQ dose >5 mg/kg/day, which led to ophthalmology guidelines recommending the avoidance of HCQ dosing >5 mg/kg.1 However, whether this dosing recommendation is applicable to the future risk of HCQ retinopathy is unknown, as is the incidence of severe bullseye retinopathy vs. the mild, pre-symptomatic stage. Furthermore, recent studies have indicated that the use of lower doses of HCQ may increase the risk of lupus flares and hospitalizations.2ObjectivesTo determine the incidence of HCQ retinopathy associated with long-term HCQ use and compare them according to HCQ dose.MethodsWe emulated a hypothetical target trial using observational data3 from the US integrated health network Kaiser Permanente Northern California to compare two HCQ weight-based dosing strategies, >5 vs ≤5 mg/kg/day, based on dispensed tablets per year. A secondary analysis evaluated >80% of prescription days covered by dispensed tablets per year with HCQ dose >5 vs ≤5 mg/kg. We included 4,677 patients who initiated and continued HCQ for at least 5 years between 1997-2020. We emulated randomization of treatment strategy by cloning each subject and assigning a replicate to each treatment group.3 We censored replicates if and when they deviated from the assigned treatment group, assessed as the average dose in the first 5 years and annually thereafter. We used inverse probability weighting to account for censoring. The primary outcome was HCQ retinopathy, assessed by expert adjudication of spectral domain-optical coherence tomography (SD-OCT) and graded by severity. All SD-OCTs were prospectively reviewed by an expert ophthalmologist (RM), and a second expert ophthalmologist (MM) reviewed all abnormal scans and a random subset of normal scans. We assessed intra-rater reliability of SD-OCT findings. We used pooled logistic regression to estimate the cumulative incidence of HCQ retinopathy for each HCQ dose strategy from initiation. The odds ratios approximated hazard ratios (HRs) because the outcome at each one-year time block is <5%.ResultsAmong 4,677 patients, the mean age at HCQ initiation was 52 years; 83% were female. The racial/ethnic composition included 51% non-Hispanic White, 19% Hispanic, 14% Asian, and 11% Black patients. 756 (16.2%) and 3,921 (83.8%) patients initiated HCQ with the primary definition of the treatment strategies >5 and ≤5 mg/kg/day, respectively. The weighted kappa was 0.80 for SD-OCT reliability. 164 patients developed HCQ retinopathy (100 mild, 38 moderate, and 26 severe cases). The cumulative incidence of retinopathy over 18 years was 37.6% for >5 and 5.7% for ≤5mg/kg of HCQ in our primary analysis. The corresponding risk was 26.5% for >5 and 3.2% for ≤5 mg/kg in our secondary analysis using >80% of prescription days. Compared with ≤5 mg/kg of HCQ, the HRs of retinopathy were 9.65 (95% CI 5.73-16.65) and 10.79 (95% CI 6.40-20.07) for >5 mg/kg using the primary and secondary definitions of HCQ dose categories, respectively (Figure 1).ConclusionThe risk of HCQ retinopathy associated with long-term adherence to >5 mg/kg dosing was high, approximately 10 times that of ≤5 mg/kg dosing. However, most cases identified during the study were mild and pre-symptomatic, supporting the value of regular screening. These data should be incorporated into individualized decisions about long-term use of HCQ.References[1]Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol 2014;132(12):1453-60[2]Almeida-Brasil CC et al. Flares after hydroxychloroquine reduction or discontinuation: results from the SLICC inception cohort. Ann Rheum Dis 2021 Dec 15, epub ahead of print[3]Hernán MA, Robins JM. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. Am J Epidemiol 2016;183(8):758-64Disclosure of InterestsApril Jorge: None declared, Ronald Melles: None declared, Michael Marmor: None declared, Carol Conell: None declared, Baijun Zhou: None declared, Jingbo Niu: None declared, Yuqing Zhang: None declared, Hyon Choi Consultant of: Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart., Grant/research support from: Ironwood and Horizon

As one of the members of the Organisation of Islamic Corporation (OIC), Indonesia has excellent trade prospects. Therefore, this study has a purpose to examine the impact of macroeconomics factors on trade between Indonesia and intra-OIC countries. The variables of macroeconomics in this study consist of country risks, inflation, exchange rate, oil price, and economic growth. Quantitative is the right method for this study, applying Ordinary Least Square (OLS) regression with the help of EViews. The data used for the analysis is a time horizon with annual frequency from 1986 to 2016. Furthermore, finding shows that almost all variables of macroeconomics play an insignificant role in determining the trade between Indonesia and Islamic countries. However, the oil price is the only variable to show its contribution towards trade between Indonesia and intra-OIC countries. The results indicate that macroeconomic variables do not contribute to the key decisions for conducting trade internationally. Political factors and bilateral treaties become better variables to explain Indonesia's trade with other Islamic countries.

In our work, based on the archival data of observations carried out in 1955 – 2015, hydrological and hydrochemical characteristics in the 10–30 m layer in the northwestern shelf (NWS) of the Black Sea, including the Danube estuary area are analyzed. Intra-annual changes in dissolved oxygen and water temperature in the NWS and in the Danube estuary area are shown to have a well-pronounced seasonal character. Water temperature in the estuary area of the Danube is characterized by lower values in all seasons than in the NWS. Salinity at the horizons of 10 and 20 m in winter in the estuary area of the Danube is lower than in the NWS due to the freshening of the upper mixed layer by river runoff. In spring, resulting from increased river runoff, an increase in the stability of water stratification occurs, which prevents the spread of heat inland and vertical exchange of oxygen. The strongest freshening in the studied layer is established at the horizon of 10 m. In spring, the southerly winds “trap” river waters in the shallower part of the shelf, and westerly winds give rise to the spread of freshened waters to the east. The summer-autumn period is characterized by low intensity of vertical and horizontal water exchange, which reduces the flow of oxygen to the subsurface layers. Harmonic analysis shows that in the Danube estuary area and in the NWS, the annual signal is dominant for temperature, salinity and oxygen, except for salinity at the 30 m horizon in the estuary area of the Danube. The semiannual harmonic of salinity at 30 m in the estuarine area of the Danube is most likely related to both limited data availability and their noisiness.

Accurate glucose prediction along a long-enough time horizon is a key component for technology to improve type 1 diabetes treatment. Subjects with diabetes might benefit from supervision and control systems that accurately predict risks and trigger corrective actions early enough with improved mitigation. However, large intra-patient variability poses big challenges to glucose prediction. In previous works by the authors, clustering and local modeling techniques with seasonal stochastic models proved to be efficient, allowing for good glucose prediction accuracy for long prediction horizons. Continuous glucose monitoring (CGM) data were partitioned into fixed-length postprandial time subseries and clustered with Fuzzy C-Means to collect similar behaviors, enforcing seasonality at each cluster after subseries concatenation. Then, seasonal stochastic models were identified for each cluster and local predictions were integrated into a global prediction. However, free-living conditions do not support the fixed-length partition of CGM data since daily events duration is variable. In this work, a new algorithm is provided to overcome this constraint, allowing better coping with patient’s variability under variable-length time-stamped daily events in supervision and control applications. Besides predicted glucose, two real-time indices are additionally provided—a crispness index, indicating good representation of current glucose behavior by a single model, and a normality index, allowing for the detection of an abnormal glucose behavior (unusual according to registered historical data). The framework is tested in a proof-of-concept in silico study with ten patients over four month training data and two independent two month validation datasets, with and without abnormal behaviors, from the distribution version of the UVA/Padova simulator extended with diverse sources of intra-patient variability.

ABSTRACT In the early stages of development of the Permian Unayzah A gas reservoir at South Haradh, difficulties in intra-reservoir wireline log correlation, poor seismic character, and the recognition of multiple gas-water contacts, necessitated a detailed (core- and image log-based) geological study of the reservoir. This study revealed that the Unayzah A can be divided into two stratal units. The lower unit has poor reservoir quality. It consists of a thin, discontinuous basal eolian dune sandstone that is abruptly overlain by up to 70 ft (21 m) of very fine-grained and silty, irregularly laminated sandstones. These sediments were deposited in a very shallow ephemeral (playa) lake setting. They terminate upwards in a thin but widespread upward-fining interval that represents the Maximum Extent of the Lake (MEL horizon). In the upper unit several facies of varying reservoir quality are recognized, representing deposits that were laid down in a “mixed” eolian depositional system. Although these facies are generally common to all of the studied wells, they vary significantly in their proportions and associations from well to well. Thus a number of depositional settings are identified, which pass southwards across the study area from erg-center, eolian dune cross-bedded sandstones in the north (“dry” eolian system) through erg margin, interbedded dune and interdune deposits to very finegrained sandstones representing ephemeral lake sediments in the south (“wet” eolian system). Depositional cycles in the upper Unayzah A interval are recognized among the facies in each well, and in every case these can be related to fluctuations in the paleo-water table. When the wells are displayed in a stratigraphic section using the MEL horizon as a datum, several of these cycles are seen to be correlatable across the study area. Significantly, these sub-regional correlations are maintained both within and between the various facies tracts. They are allostratigraphic in nature with facies distribution controlled by a number of extrinsic factors including position of the paleo-water table relative to the depositional surface, rates of fluctuation of the water table, sediment availability for eolian transportation, transporting capability of the wind and rates of subsidence. Proximity to local ephemeral stream sedimentation was probably also a factor. It may be that in the long term the pulsed nature of the rising water table in South Haradh reflects the onset of a distant, pulsed rise in sea level, possibly related to the creation of the Neo-Tethys Ocean in the southern and eastern part of the Arabian Plate. Recognition of this allostratigraphic reservoir layering clearly identifies significant stratigraphic compartmentalization within the reservoir. This permits a clearer understanding of the distribution of reservoir bodies within the Unayzah A, and explains the variable gas-water contacts in the area. This conceptual stratigraphic model has been incorporated in object-based geocellular modeling for reservoir simulation at South Haradh and also at other Unayzah A gas fields in the area. Integration with geophysical (impedance) data leads to significantly improved success rates in relation to the strategic location of wells, yielding enhanced results in reservoir development.

This paper is meant to study the apocalyptic scenario of the at the perspectives of the Great Acceleration. the apocalyptic scenario is not a pure imagination of the literature works. Instead, scientific evidences are in favour of dramatic change in the climatic conditions related to the climax of Man actions. the modelling of the future climate leads to horrible situations including intolerable temperatures, dryness, tornadoes, and noticeable sear level rise evading coastal regions. Going far from these scientific claims, Homo Sapiens Sapiens extended his imagination through the Climate-Fiction (cli-fi) to propose a dramatic end. Climate Fiction is developed into a recording machine containing every kind of fictions that depict environmental condition events and has consequently lost its true significance. Introduction The Great Acceleration may be considered as the Late Anthropocene in which Man actions reached their climax to lead to dramatic climatic changes paving the way for a possible apocalyptic scenario threatening the existence of the humanity. So, the apocalyptic scenario is not a pure imagination of the literature works. Instead, many scientific arguments especially related to climate change are in favour of the apocalypse1. As a matter of fact, the modelling of the future climate leads to horrible situations including intolerable temperatures (In 06/07/2021, Kuwait recorded the highest temperature of 53.2 °C), dryness, tornadoes, and noticeable sear level rise evading coastal regions. These conditions taking place during the Great Acceleration would have direct repercussions on the human species. Considering that the apocalyptic extinction had really caused the disappearance of many stronger species including dinosaurs, Homo Sapiens Sapiens extended his imagination though the Climate-Fiction (cli-fi) to propose a dramatic end due to severe climate conditions intolerable by the humankind. The mass extinction of animal species has occurred several times over the geological ages. Researchers have a poor understanding of the causes and processes of these major crises1. Nonetheless, whatever the cause of extinction, the apocalyptic scenario has always been present in the geological history. For example, dinosaurs extinction either by asteroids impact or climate changes could by no means denies the apocalyptic aspect2.At the same time as them, many animal and plant species became extinct, from marine or flying reptiles to marine plankton. This biological crisis of sixty-five million years ago is not the only one that the biosphere has suffered. It was preceded and followed by other crises which caused the extinction or the rarefaction of animal species. So, it is undeniable that many animal groups have disappeared. It is even on the changes of fauna that the geologists of the last century have based themselves to establish the scale of geological times, scale which is still used. But it is no less certain that the extinction processes, extremely complex, are far from being understood. We must first agree on the meaning of the word "extinction", namely on the apocalyptic aspect of the concept. It is quite understood that, without disappearances, the evolution of species could not have followed its course. Being aware that the apocalyptic extinction had massacred stronger species that had dominated the planet, Homo Sapiens Sapiens has been aware that the possibility of apocalyptic end at the perspective of the Anthropocene (i.e., Great Acceleration) could not be excluded. This conviction is motivated by the progressive defaunation in some regions3and the appearance of alien species in others related to change of mineralogy and geochemistry4 leading to a climate change during the Anthropocene. These scientific claims fed the vast imagination about climate change to set the so-called cli-fi. The concept of the Anthropocene is the new geological era which begins when the Man actions have reached a sufficient power to modify the geological processes and climatic cycles of the planet5. The Anthropocene by no means excludes the possibility of an apocalyptic horizon, namely in the perspectives of the Great Acceleration. On the contrary, two scenarios do indeed seem to dispute the future of the Anthropocene, with a dramatic cross-charge. The stories of the end of the world are as old as it is, as the world is the origin of these stories. However, these stories of the apocalypse have evolved over time and, since the beginning of the 19th century, they have been nourished particularly by science and its advances. These fictions have sometimes tried to pass themselves off as science. This is the current vogue, called collapsology6. This end is more than likely cli-fi driven7and it may cause the extinction of the many species including the Homo Sapiens Sapiens. In this vein, Anthropocene defaunation has become an ultimate reality8. More than one in eight birds, more than one in five mammals, more than one in four coniferous species, one in three amphibians are threatened. The hypothesis of a hierarchy within the living is induced by the error of believing that evolution goes from the simplest to the most sophisticated, from the inevitably stupid inferior to the superior endowed with an intelligence giving prerogative to all powers. Evolution goes in all directions and pursues no goal except the extension of life on Earth. Evolution certainly does not lead from bacteria to humans, preferably male and white. Our species is only a carrier of the DNA that precedes us and that will survive us. Until we show a deep respect for the biosphere particularly, and our planet in general, we will not become much, we will remain a predator among other predators, the fiercest of predators, the almighty craftsman of the Anthropocene. To be in the depths of our humanity, somehow giving back to the biosphere what we have taken from it seems obvious. To stop the sixth extinction of species, we must condemn our anthropocentrism and the anthropization of the territories that goes with it. The other forms of life also need to keep their ecological niches. According to the first, humanity seems at first to withdraw from the limits of the planet and ultimately succumb to them, with a loss of dramatic meaning. According to the second, from collapse to collapse, it is perhaps another humanity, having overcome its demons, that could come. Climate fiction is a literary sub-genre dealing with the theme of climate change, including global warming. The term appears to have been first used in 2008 by blogger and writer Dan Bloom. In October 2013, Angela Evancie, in a review of the novel Odds against Tomorrow, by Nathaniel Rich, wonders if climate change has created a new literary genre. Scientific basis of the apocalyptic scenario in the perspective of the Anthropocene Global warming All temperature indices are in favour of a global warming (Fig.1). According to the different scenarios of the IPCC9, the temperatures of the globe could increase by 2 °C to 5 °C by 2100. But some scientists warn about a possible runaway of the warming which can reach more than 3 °C. Thus, the average temperature on the surface of the globe has already increased by more than 1.1 °C since the pre-industrial era. The rise in average temperatures at the surface of the globe is the first expected and observed consequence of massive greenhouse gas emissions. However, meteorological surveys record positive temperature anomalies which are confirmed from year to year compared to the temperatures recorded since the middle of the 19th century. Climatologists point out that the past 30 years have seen the highest temperatures in the Northern Hemisphere for over 1,400 years. Several climatic centres around the world record, synthesize and follow the evolution of temperatures on Earth. Since the beginning of the 20th century (1906-2005), the average temperature at the surface of the globe has increased by 0.74 °C, but this progression has not been continuous since 1976, the increase has clearly accelerated, reaching 0.19 °C per decade according to model predictions. Despite the decline in solar activity, the period 1997-2006 is marked by an average positive anomaly of 0.53 °C in the northern hemisphere and 0.27 °C in the southern hemisphere, still compared to the normal calculated for 1961-1990. The ten hottest years on record are all after 1997. Worse, 14 of the 15 hottest years are in the 21st century, which has barely started. Thus, 2016 is the hottest year, followed closely by 2015, 2014 and 2010. The temperature of tropical waters increased by 1.2 °C during the 20th century (compared to 0.5 °C on average for the oceans), causing coral reefs to bleach in 1997. In 1998, the period of Fort El Niño, the prolonged warming of the water has destroyed half of the coral reefs of the Indian Ocean. In addition, the temperature in the tropics of the five ocean basins, where cyclones form, increased by 0.5 °C from 1970 to 2004, and powerful cyclones appeared in the North Atlantic in 2005, while they were more numerous in other parts of the world. Recently, mountains of studies focused on the possible scenario of climate change and the potential worldwide repercussions including hell temperatures and apocalyptic extreme events10 , 11, 12. Melting of continental glaciers As a direct result of the global warming, melting of continental glaciers has been recently noticed13. There are approximately 198,000 mountain glaciers in the world; they cover an area of approximately 726,000 km2. If they all melted, the sea level would rise by about 40 cm. Since the late 1960s, global snow cover has declined by around 10 to 15%. Winter cold spells in much of the northern half of the northern hemisphere are two weeks shorter than 100 years ago. Glaciers of mountains have been declining all over the world by an average of 50 m per decade for 150 years. However, they are also subject to strong multi-temporal variations which make forecasts on this point difficult according to some specialists. In the Alps, glaciers have been losing 1 meter per year for 30 years. Polar glaciers like those of Spitsbergen (about a hundred km from the North Pole) have been retreating since 1880, releasing large quantities of water. The Arctic has lost about 10% of its permanent ice cover every ten years since 1980. In this region, average temperatures have increased at twice the rate of elsewhere in the world in recent decades. The melting of the Arctic Sea ice has resulted in a loss of 15% of its surface area and 40% of its thickness since 1979. The record for melting arctic sea ice was set in 2017. All models predict the disappearance of the Arctic Sea ice in summer within a few decades, which will not be without consequences for the climate in Europe. The summer melting of arctic sea ice accelerated far beyond climate model predictions. Added to its direct repercussions of coastal regions flooding, melting of continental ice leads to radical climatic modifications in favour of the apocalyptic scenario. Fig.1 Evolution of temperature anomaly from 1880 to 2020: the apocalyptic scenario Sea level rise As a direct result of the melting of continental glaciers, sea level rise has been worldwide recorded14 ,15. The average level of the oceans has risen by 22 cm since 1880 and 2 cm since the year 2000 because of the melting of the glaciers but also with the thermal expansion of the water. In the 20th century, the sea level rose by around 2 mm per year. From 1990 to 2017, it reached the relatively constant rate of just over 3mm per year. Several sources contributed to sea level increase including thermal expansion of water (42%), melting of continental glaciers (21%), melting Greenland glaciers (15%) and melting Antarctic glaciers (8%). Since 2003, there has always been a rapid rise (around 3.3 mm / year) in sea level, but the contribution of thermal expansion has decreased (0.4 mm / year) while the melting of the polar caps and continental glaciers accelerates. Since most of the world’s population is living on coastal regions, sea level rise represents a real threat for the humanity, not excluding the apocalyptic scenario. Multiplication of extreme phenomena and climatic anomalies On a human scale, an average of 200 million people is affected by natural disasters each year and approximately 70,000 perish from them. Indeed, as evidenced by the annual reviews of disasters and climatic anomalies, we are witnessing significant warning signs. It is worth noting that these observations are dependent on meteorological survey systems that exist only in a limited number of countries with statistics that rarely go back beyond a century or a century and a half. In addition, scientists are struggling to represent the climatic variations of the last two thousand years which could serve as a reference in the projections. Therefore, the exceptional nature of this information must be qualified a little. Indeed, it is still difficult to know the return periods of climatic disasters in each region. But over the last century, the climate system has gone wild. Indeed, everything suggests that the climate is racing. Indeed, extreme events and disasters have become more frequent. For instance, less than 50 significant events were recorded per year over the period 1970-1985, while there have been around 120 events recorded since 1995. Drought has long been one of the most worrying environmental issues. But while African countries have been the main affected so far, the whole world is now facing increasingly frequent and prolonged droughts. Chile, India, Australia, United States, France and even Russia are all regions of the world suffering from the acceleration of the global drought. Droughts are slowly evolving natural hazards that can last from a few months to several decades and affect larger or smaller areas, whether they are small watersheds or areas of hundreds of thousands of square kilometres. In addition to their direct effects on water resources, agriculture and ecosystems, droughts can cause fires or heat waves. They also promote the proliferation of invasive species, creating environments with multiple risks, worsening the consequences on ecosystems and societies, and increasing their vulnerability. Although these are natural phenomena, there is a growing understanding of how humans have amplified the severity and impacts of droughts, both on the environment and on people. We influence meteorological droughts through our action on climate change, and we influence hydrological droughts through our management of water circulation and water processes at the local scale, for example by diverting rivers or modifying land use. During the Anthropocene (the present period when humans exert a dominant influence on climate and environment), droughts are closely linked to human activities, cultures, and responses. From this scientific overview, it may be concluded apocalyptic scenario is not only a literature genre inspired from the pure imagination. Instead, many scientific arguments are in favour of this dramatic destiny of Homo Sapiens Sapiens. Fig.2. Sea level rise from 1880 to 2020: a possible apocalyptic scenario (www.globalchange.gov, 2021) Apocalyptic genre in recent writing As the original landmark of apocalyptic writing, we must place the destruction of the Temple of Jerusalem in 587 BC and the Exile in Babylon. Occasion of a religious and cultural crossing with imprescriptible effects, the Exile brought about a true rebirth, characterized by the maintenance of the essential ethical, even cultural, of a national religion, that of Moses, kept as pure as possible on a foreign land and by the reinterpretation of this fundamental heritage by the archaic return of what was very old, both national traditions and neighbouring cultures. More precisely, it was the place and time for the rehabilitation of cultures and the melting pot for recasting ancient myths. This vast infatuation with Antiquity, remarkable even in the vocabulary used, was not limited to Israel: it even largely reflected a general trend. The long period that preceded throughout the 7th century BC and until 587, like that prior to the edict of Cyrus in 538 BC, was that of restorations and rebirths, of returns to distant sources and cultural crossings. In the biblical literature of this period, one is struck by the almost systematic link between, on the one hand, a very sustained mythical reinvestment even in form and, on the other, the frequent use of biblical archaisms. The example of Shadday, a word firmly rooted in the Semites of the Northwest and epithet of El in the oldest layers of the books of Genesis and Exodus, is most eloquent. This term reappears precisely at the time of the Exile as a designation of the divinity of the Patriarchs and of the God of Israel; Daily, ecological catastrophes now describe the normal state of societies exposed to "risks", in the sense that Ulrich Beck gives to this term: "the risk society is a society of catastrophe. The state of emergency threatens to become a normal state there1”. Now, the "threat" has become clearer, and catastrophic "exceptions" are proliferating as quickly as species are disappearing and climate change is accelerating. The relationship that we have with this worrying reality, to say the least, is twofold: on the one hand, we know very well what is happening to us; on the other hand, we fail to draw the appropriate theoretical and political consequences. This ecological duplicity is at the heart of what has come to be called the “Anthropocene”, a term coined at the dawn of the 21st century by Eugene Stoermer (an environmentalist) and Paul Crutzen (a specialist in the chemistry of the atmosphere) in order to describe an age when humanity would have become a "major geological force" capable of disrupting the climate and changing the terrestrial landscape from top to bottom. If the term “Anthropocene” takes note of human responsibility for climate change, this responsibility is immediately attributed to overpowering: strong as we are, we have “involuntarily” changed the climate for at least two hundred and fifty years. Therefore, let us deliberately change the face of the Earth, if necessary, install a solar shield in space. Recognition and denial fuel the signifying machine of the Anthropocene. And it is precisely what structures eco-apocalyptic cinema that this article aims to study. By "eco-apocalyptic cinema", we first mean a cinematographic sub-genre: eco-apocalyptic and post-eco-apocalyptic films base the possibility (or reality) of the end of the world on environmental grounds and not, for example, on damage caused by the possible collision of planet Earth with a comet. Post-apocalyptic science fiction (sometimes abbreviated as "post-apo" or "post-nuke") is a sub-genre of science fiction that depicts life after a disaster that destroyed civilization: nuclear war, collision with a meteorite, epidemic, economic or energy crisis, pandemic, alien invasion. Conclusion Climate and politics have been linked together since Aristotle. With Montesquieu, Ibn Khaldûn or Watsuji, a certain climatic determinism is attributed to the character of a nation. The break with modernity made the climate an object of scientific knowledge which, in the twentieth century, made it possible to document, despite the controversies, the climatic changes linked to industrialization. Both endanger the survival of human beings and ecosystems. Climate ethics are therefore looking for a new relationship with the biosphere or Gaia. For some, with the absence of political agreements, it is the beginning of inevitable catastrophes. For others, the Anthropocene, which henceforth merges human history with natural history, opens onto technical action. The debate between climate determinism and human freedom is revived. The reference to the biblical Apocalypse was present in the thinking of thinkers like Günther Anders, Karl Jaspers or Hans Jonas: the era of the atomic bomb would mark an entry into the time of the end, a time marked by the unprecedented human possibility of 'total war and annihilation of mankind. The Apocalypse will be very relevant in describing the chaos to come if our societies continue their mad race described as extra-activist, productivist and consumerist. In dialogue with different theologians and philosophers (such as Jacques Ellul), it is possible to unveil some spiritual, ethical, and political resources that the Apocalypse offers for thinking about History and human engagement in the Anthropocene. What can a theology of collapse mean at a time when negative signs and dead ends in the human situation multiply? What then is the place of man and of the cosmos in the Apocalypse according to Saint John? Could the end of history be a collapse? How can we live in the time we have left before the disaster? Answers to such questions remain unknown and no scientist can predict the trajectory of this Great Acceleration taking place at the Late Anthropocene. When science cannot give answers, Man tries to infer his destiny for the legend, religion and the fiction. Climate Fiction is developed into a recording machine containing every kind of fictions that depict environmental condition events and has consequently lost its true significance. Aware of the prospect of ecological collapse additionally as our apparent inability to avert it, we tend to face geology changes of forceful proportions that severely challenge our ability to imagine the implications. Climate fiction ought to be considered an important supplement to climate science, as a result, climate fiction makes visible and conceivable future modes of existence inside worlds not solely deemed seemingly by science, however that area unit scientifically anticipated. 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AbstractNature-based solutions (NBS) are increasingly at the centre of urban strategies to mitigate heatwaves and flooding, improve public health and restore biodiversity. However, on-ground implementation has been slow, inconsistent and often limited to demonstration sites. A broad literature consistently highlights institutional barriers as a major reason for the observed implementation gap. In this study, we developed and deployed an assessment tool to identify barriers to NBS delivery on a European Commission Horizon 2020 project spanning seven cities. We found that practitioners were effectively navigating challenges in the areas where they had significant control, including community engagement, strategy development and technical skills. The greatest barriers were outside the influence of project teams: understaffing, a lack of intra-organisational processes, and risk-averse organisational cultures. These findings emphasise that after cities embrace NBS at the strategic and political level, it is vital that executives follow through with the necessary pragmatic reforms to enable delivery.

Osteoarthritis (OA) is the fastest growing cause of disability worldwide, but, with few proven therapeutic options, it is an underserved condition. With increasingly ageing populations contributing to a rising global prevalence, this unmet need only threatens to worsen in the coming years. To date, researchers have tried and failed in their bids to develop new ways to treat the pain and loss of function that significantly impacts health-related quality of life (HrQoL) and leaves people vulnerable to accumulating disability and at risk of cardiovascular disease (CVD), comorbidities, and mortality. Now, a novel way to deliver one of the only proven interventions for pain and inflammation, corticosteroid injections, is on the horizon for knee OA. Slow-release formulations could possibly prolong the clinical benefit of a single injection from 6 weeks to 6 months, providing a new option to improve HrQoL for people with OA, and maybe even breaking the cycle of inflammation that likely contributes to progression. In this key opinion leader article, Philip Conaghan and Lee Simon discuss OA’s significant Quality of life (QoL) and long-term health impact. They also outline the current, inadequate treatment landscape, and explain how slow-release corticosteroids could potentially help tackle a huge unmet medical need.

Abstract Background Desirability of outcome ranking (DOOR) uses an ordinal ranking system to evaluate global outcomes in clinical trial participants by incorporating safety and efficacy assessments into a single endpoint. In this study, we developed and applied a DOOR endpoint for cIAI clinical trials. Methods We reviewed 10 Phase 3 noninferiority trials for cIAI with electronic patient-level data (n=5473 participants) submitted to the FDA between 2005-2021. Extending previous work [CID. 2019:68(10):1691-8)], we developed an expanded cIAI-specific DOOR endpoint based on clinically meaningful events captured in trial datasets and those that were unique to patients with cIAI. Using this DOOR endpoint, we assigned each participant a DOOR rank, estimated the probability that a participant in the study treatment arm in each trial would have a more desirable DOOR rank than if assigned to the comparator arm, and analyzed individual components of clinical experience in each trial. Results Based on analysis of available data, we noted heterogeneity in definitions of “indeterminate” clinical outcomes, and significant diversity and increased incidence of infectious complications (ICs), serious adverse events (SAEs), and surgical/percutaneous procedures in participants without clinical cure. These informed the expansion of the DOOR endpoint for cIAI to include clinical efficacy outcomes, ICs, SAEs, and additional procedures (Table 1). The DOOR distributions between treatment and comparator arms in all 10 trials were similar. DOOR probability estimates for the 10 trials ranged from 44.5% to 50.3% but were not nominally statistically significant. Component analyses in two trials showed that the study treatment was nominally statistically inferior to the comparator with regard to SAEs and clinical failure, respectively (Fig. 1b, 1c). Table 1.cIAI-Specific DOOR EndpointFigure 1.Forest plot listing the DOOR probabilities and probability for each DOOR component from 3 trials. Trial 1 has no significant differences between the treatment arms in the component analysis (A). The study treatment arm was shown to be nominally statistically inferior for SAEs in Trial 2 (B) and for clinical failure in Trial 3 (C). Conclusion We developed a cIAI-specific DOOR endpoint to better elucidate the events that participants experienced in these trials. The component analysis allowed more nuanced evaluation of the factors that contributed to the composite DOOR probability estimate and provided a visual display of the risk-benefit assessment of a study treatment vs. the comparator. Our study was limited by its retrospective approach and trial design heterogeneity. Disclosures Deborah Collyar, B.Sci, Apellis Pharmaceuticals, Inc.: Advisor/Consultant|Kinnate Biopharma: Advisor/Consultant|M2GEN: Advisor/Consultant|Maxis Clinical Sciences: Advisor/Consultant|Parexel: Honoraria|Pfizer: Honoraria|Roundtable Analytics, Inc.: Ownership Interest Sarah B. Doernberg, MD, MAS, Basilea: Clincal events committee|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clincal events committee Scott R. Evans, Ph.D., M.S., Abbvie: DSMB|Akouos: DSMB|Apellis: DSMB|AstraZeneca: Advisor/Consultant|Atricure: Advisor/Consultant|Becton Dickenson: Advisor/Consultant|Breast International Group: DSMB|Candel: DSMB|ChemoCentrix: Advisor/Consultant|Clover: DSMB|DayOneBio: DSMB|DeGruyter: Editor|Duke University: DSMB|Endologix: Advisor/Consultant|FHI Clinical: DSMB|Genentech: Advisor/Consultant|Horizon: Advisor/Consultant|International Drug Development Institute: Advisor/Consultant|Janssen: Advisor/Consultant|Lung Biotech: DSMB|Neovasc: Advisor/Consultant|NIH: Grant/Research Support|Nobel Pharma: Advisor/Consultant|Nuvelution: DSMB|Pfizer: DSMB|Rakuten: DSMB|Roche: DSMB|Roivant: Advisor/Consultant|SAB Biopharm: DSMB|SVB Leerink: Advisor/Consultant|Takeda: DSMB|Taylor & Francis: Book royalties|Teva: DSMB|Tracon: DSMB|University of Penn: DSMB|Vir: DSMB Thomas L. Holland, MD, Aridis: Advisor/Consultant|Lysovant: Advisor/Consultant Henry Chambers, MD, Merck: DSMB member|Merck: Stocks/Bonds|Moderna: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Sumathi Nambiar, MD MPH, Johnson and Johnson: Stocks/Bonds Helen W. Boucher, MD, American Society of Microbiology: Honoraria|Elsevier: Honoraria|Sanford Guide: Honoraria.