Human Occupation Research Articles

Competing forces: Subsistence strategies and human-carnivore interactions during the middle to Upper Palaeolithic transition in Northern Iberia

The comparative assessment of dietary choices as part of landscape use strategies deployed by Neanderthal and Anatomically Modern Human populations in Eurasia constitutes a fundamental avenue of Palaeolithic research. The increasing number of taphonomic assessments enables a better understanding of what remains were brought to sites by human hunters versus mammalian carnivores or raptors. A zooarchaeological approach can further elucidate the spatio-temporal dynamics of interaction between carnivores and human populations in terms of landscape use and prey choice during this transitional period. To achieve this objective, we conducted an examination of zooarchaeological and taphonomic data, carnivore indices, and other relevant variables across 36 Middle and Early Upper Palaeolithic sites in northern Iberia. These sites encompass 126 archaeological layers dating from 50,000 to 30,000 years ago. Our comprehensive bibliographic meta-analysis reveals that human occupations by both groups at sites across the region were punctuated by episodes influenced by carnivores. This observation implies that human occupations in northern Iberia during Marine Isotope Stage 3 were generally characterised by instability and limited to short periods, often seasonal in nature. From a zooarchaeological perspective, the combined assessment of taxonomic data, species richness and assemblage diversity highlights that the range and proportion of species acquired by these different human groups are similar, although Anatomically Modern Humans engaged in a sustained trend towards increasing dietary diversification even at sites with assemblages heavily dominated by one taxon.

Climatic and disturbance impacts on temperate rainforest development since ∼18 ka in central-west Isla Grande de Chiloé (42.7°S)

Understanding the role of disturbance regimes on terrestrial ecosystems is often compounded by the paucity of time series sufficiently long and detailed to capture triggering events and the sequence of changes in species composition, community structure and dynamics along a time continuum until the present. Adding complexity to this problem, disturbance regimes and the distribution/competitive interactions of participating species may vary in time with shifts in mean climatic conditions and variability. Here we present results from sediment cores we collected from small closed-basin lakes near the Pacific coast of central Isla Grande de Chiloé, a sector with the lowest seasonality and recurrence of explosive volcanic events in Northwestern Patagonia (NWP). Our aim is examining vegetation development since the last glaciation and exploring potential climatic and disturbance impacts. We found rapid establishment of closed-canopy rainforests, which have persisted with little variation in terms of physiognomy until the present. Significant changes in species composition, structure, dynamics, and rates of change are evident over the last ∼18,000 years, along with fire maxima at ∼16.7 ka, ∼12.7 ka, between ∼11.7-9 ka, from ∼2 ka to the present, and minima in the interim. Fires precede major increases in disturbance favored taxa, which correspond in timing with fire activity maxima at NWP scale. The most recent ∼2000 years coincide with the highest number and ubiquity of human occupations at central-west and NWP scale, raising the possibility that fires were driven by human activities near our study sites. We detect a conspicuous increase in disturbance-favored trees ∼150 years after deposition of the Puma Verde Tephra (∼8.3 ka) and interpret their subsequent maintenance by frequent blowdown events after ∼7.5 ka in exposed sectors of the Coastal Range. We posit that enhanced storminess driven by stronger Southern Westerly Winds since ∼7.5 ka has favored early successional opportunistic trees in detriment of old-growth forests dominated by shade-tolerant species, generating a spatial mosaic of forest patches or gaps in different stages of recovery.

Artisanal and small-scale gold mining and biodiversity: a global literature review.

Artisanal and small-scale gold mining (ASGM) is crucial to the livelihoods of close to 20 million people in over 80 countries, including 4-5 million women, mainly in rural areas with limited alternative economic prospects, particularly in developing countries. ASGM is largely informal, which can add to the challenge of addressing negative social and environmental effects including impacts on biodiversity. However, with proper guidance, ASGM can operate in a responsible manner, using cleaner production methods that minimize impacts on human health and the environment. This study presents and analyzes the interactions between ASGM and biodiversity based on new findings from 27 ASGM National Action Plans (NAPs) developed within the framework of Article 7 and Annex C of the Minamata Convention on Mercury, as well as a global literature review of more than 100 publications. In terms of key findings according to the literature reviewed, alongside other human occupation such as agriculture and industrial activities, ASGM also has an impact on the environment and biodiversity. The interrelationship between ASGM and biodiversity, including protected areas, is pervasive at every stage of ASGM operations, from extraction to mine closure, and generates significant impacts on the surrounding ecosystems. These impacts include, in descending order of most reported impacts: deforestation, soil degradation, chemical contamination of aquatic and terrestrial systems, and changes to the turbidity of watercourses. Tropical regions and key species such as amphibians and freshwater fish are among the most affected. Singly or combined, these environmental stressors lead to loss or deterioration of habitat and, by extension, indigenous biodiversity and ecosystem services. In addition, legal, institutional, and regulatory frameworks and related measures, inadequate or non-existent in some cases, may not necessarily support sustainable practices, often resulting in exploited sites abandoned without remediation, reclamation, rehabilitation, or restoration measures. To mitigate such impacts a key recommendation arising from the literature review is to strengthen the integration of the interrelationship between ASGM and biodiversity in the implementation of existing relevant national strategies, including those developed under the NAPs. The global literature review also highlights the importance of a multi-stakeholder, systemic approach combining the use of geospatial analysis, scientific and local knowledge, as well as the adaptation of the relevant frameworks, capacity building, and awareness raising. This approach can inform decision making with a view to developing sustainable initiatives that prevent and reduce the impacts of artisanal and small-scale gold mining on ecosystems, and that preserve biodiversity.

Tracking Stone Age mariners: projecting into the past

ABSTRACT It has become increasingly clear that, through the millennia, travel by water has been generally safer, faster, and more economical than travel by land. Humans possessed seagoing watercraft early on, disablings and uncontrolled storm-generated drifts would inevitably have occurred, and the prevailing winds and oceanic surface currents would have impelled some of these craft over oceans, leading to insular and extrahemispheric discoveries and exchanges. Intentional exploratory voyages also occurred. Although there is much material evidence of developed watercraft from the Late Neolithic on, few Stone Age vessel vestiges other than of logboats have been recovered archaeologically. However, indirect means exist to obtain a sense of what occurred long ago. First is demonstration of very early human presences on islands. Here, many contemporary scientific proxies for otherwise-undocumented human occupancy are described. In the New World, the presence of tropical/subtropical human intestinal parasites implies trans-ocean crossings impressively early in time, including by the seventh millennium B.C.

FOREST FIRES RISK IN A SEMI ARID REGION: A CASE STUDY IN WESTERN ALGERIA

Purpose: The objective of this study was to measure the fire risk of forests and to compare areas with high sensitivity to forest fires.   Theoretical Framework: Many authors have demonstrated the fragility of Algerian forests in the face of fires (Belhadj, 2003; Souidi et al., 2010 and 2017). In this research paper, the researchers focused on identifying the factors responsible for the risk of forest fires in Algeria using a state-of-the-art tool, the Geographic Information System (GIS). The researchers explained a scientific process for exploring new indicators using GIS, and showed how to develop a forest fire risk map.   Design/Methodology/Approach: The elaboration of the fire risk map requires the application of a model set up, and tested on forest areas in the Mediterranean region. The applied model involves the three main factors of forest fire risk assessment: topomorphology, fuel, and human occupation.   Findings: According to the results obtained, our study area is dominated by a very high risk index. In addition, more than half of the surface area of our study zone is located in topomorphological conditions that are highly conducive to the multiplication of fires and can increase the risk of forest fires breaking out. This study will help us to better control the risk of fires and to manage fire-fighting operations in the field.   Research, Practical & Social Implications: Mapping the risk of forest fires using GIS will help land managers and planners to identify sensitive areas for better preservation and intervention in the event of fire.   Originality/Value: The results show that the number of forest fires is increasing over time and that managing them is becoming increasingly difficult. The use of a GIS for all stakeholder and managers will make it possible to combat forest fires.

Analysis of the Early Pleistocene small mammals from Pirro Nord 13 (Apricena, southern Italy) and their implications for reconstructing the palaeoenvironment of the early human occupation in Europe

The Pirro Nord quarry (Apricena, Foggia, southern Italy, 41°48′6″N, 15°23′5″ E) is a well-known palaeontological and archaeological locality comprising an abundant and diverse Early Pleistocene vertebrate assemblage of mammals, birds, amphibians, and reptiles related to the Late Villafranchian and Early Biharian mammal ages. In this study, we describe the small mammal assemblages (insectivores, rodents, and bats) excavated between 2010 and 2022 to reconstruct the palaeoenvironment surrounding the site using Habitat Weighting and the Bioclimatic model methods. The rodent assemblage comprises mostly Allophaiomys cf. ruffoi, Apodemus sp., and Hystrix refossa, whereas Eliomys cf. intermedius was reported for the first time. Insectivores includes Talpa gr. minor-caeca; Asoriculus sp.; Erinaceus praeglacialis; and Sorex sp. Bats are represented by Rhinolophus ferrumequinum, Rhinolophus gr. euryale-mehelyi, Myotis gr. myotis-blythii, Myotis sp., and Miniopterus schreibersii. Landscape reconstruction attested to the presence of a rich and diverse environment with open areas and forest patches surrounding the Pirro Nord 13 site. The climate was slightly colder than that of current times in the same area, with higher precipitation. The presence of different ecosystems near the sites constituted suitable conditions for the first human dispersion in Europe, as already revealed by evidence from Barranco León D, Atapuerca TE7–14, and Fuente Nueva 3 elsewhere on the Iberian Peninsula. The study of small mammal assemblages improves our understanding of the chronological boundaries of the human occupation of Pirro Nord 13, adding important information in the context of the first peopling of the Mediterranean region between 1.6 and 1.3 million years ago.

Middle to late Holocene climate change in the monsoon-dominated southeastern Tibetan Plateau and its relationship with human activity

Aeolian deposits on the southeastern Tibetan Plateau (SETP) can provide evidence of how prehistoric humans were influenced by climatic and environmental changes in high-altitude regions. We present the results of multi-proxy analyses of a middle–late Holocene aeolian section in the SETP, together with the probability density of the ages of various cultural sites within and around the study area. Quartz optically stimulated luminescence dating provides a reliable chronology for this section, and analyses of geochemical elements, color and grain size are used to reconstruct the pattern of climate change during the middle–late Holocene. The results suggest a trend of gradually decreasing moisture from the middle Holocene (∼6 ka) onwards, followed by a slight increase at ∼2 ka, which is supported by TraCE-21 ka simulation results. These changes were closely related to variation in the Indian summer monsoon (ISM) caused by decreasing Northern Hemisphere summer insolation and an increase in the Atlantic Meridional Overturning Circulation. The variations in dust activity are inversely related with moisture and there was a significant decrease in dust activity after ∼2 ka. The drought conditions during the 4.2 ka event recorded within the section appear to be a continuation of the trend of middle–late Holocene climatic deterioration, which is superimposed on a weakening trend of the ISM. The permanent human occupation of the study area after ∼2 ka corresponded to an interval of mild and wet climate when dust activity was relatively weak. An observed correlation between the intensity of human activity and dust storms suggests that the enhancement of human activities played a significant role in increasing the occurrence of dust storms. Overall, our results provide new insights into human-environmental interactions in the SETP.

Approach and Permanent Human Occupation of Mainland Portugal Coastal Zone (1096–2021)

This paper aims to enhance the understanding of the littoralization process in mainland Portugal over a broad chronological framework. Littoralization is defined as the occupation and settlement of human communities along the coast. In this case, the analysis was based on the synchronic analysis of three chronologies: from the formation of Portugal to the settlement of the fountains (1096–1325); at the dawn of modernity, marked by the Portuguese expansion (1500–1524), with the first scientific census (1860); and in the present, with data from the last census (2021). The choice of chronology was dictated by the historical sources available and allowed us to check the trend of population dispersion both in terms of latitude and longitude, the latter being the analysis of the distance of the main population centers (counties) from the coast. In the first chronological segment, there is a “safety distance” from the exposed coastlines, which is gradually blurred over time until there is an impressive coastal demographic concentration in 2021, with around 80% of people settled within 50 km of the sea. So, the management of Portugal’s territory is an unequivocal indicator of the Anthropocene even with the risks of the disappearance of some beaches.

Impact of Indoor Air Quality and Multi-domain Factors on Human Productivity and Physiological Responses: A Comprehensive Review

Indoor environmental quality (IEQ) significantly impacts human health, well-being, and productivity. However, a comprehensive and in-depth review of the combined effects of IAQ and other multi-domain factors on human productivity is lacking. There has not been any prior review that encapsulates the impact of multi-domain factors on productivity and physiological responses of occupants. To address this gap, this review paper investigates and highlights the impact of IAQ and multi-domain factors (thermal, visual, and acoustic) on human productivity and occupant well-being in the built environment. The review explores various research methods, including evaluation of human productivity and creativity, data collection, and physiological signal analysis. We also examined the interactions between IAQ and multi-domain factors, as well as strategies for optimizing productivity through integrated building design and smart systems. The key findings from this review reveal that IAQ significantly impacts human productivity and occupant well-being, with interactions between IAQ and other IEQ factors further impacting these effects. Despite advances in the field, there are several limitations and gaps in the current research methods and study designs, including small sample sizes, limited and insufficient experimental design and control, reliance on laboratory or simulated environments, lack of follow-up and long-term data, and lack of robust performance metrics. The review proposes future research directions, including specific applications, and follow-up work to address these limitations and further advance the understanding of IAQ and multi-domain factors in the built environment. The implications of this review for policy and practice include the need for holistic and integrated approaches to IAQ and IEQ management, with a focus on creating healthy and productive indoor environments. This review emphasizes the importance of considering the complex interplay between IAQ and multi-domain factors, as well as the potentials of adopting smart control systems and sustainable design strategies to optimize productivity and occupant well-being in the built environment. By addressing these critical issues, we can enhance the overall quality of life for building occupants and contribute to a more sustainable future.

Early Beringian Traditions: Functioning and Economy of the Stone Toolkit from Swan Point CZ4b, Alaska

Abstract The pressure knapping technique develops circa 25,000 cal BP in Northeast Asia and excels at producing highly standardized microblades. Microblade pressure knapping spreads throughout most of Northeast Asia up to the Russian Arctic, and Alaska, in areas where the human presence was unknown. Swan Point CZ4b is the earliest uncontested evidence of human occupation of Alaska, at around 14,000 cal BP. It yields a pressure microblade component produced with the Yubetsu method, which is widespread in Northeast Asia during the Late Glacial period. Through the techno-functional analysis of 634 lithic pieces from this site, this study seeks to identify the techno-economical purposes for which the Yubetsu method was implemented. Data show that the microblade production system is related to an economy based on the planning of future needs, which is visible through blanks standardization, their overproduction, their functional versatility, and the segmentation of part of the chaîne opératoire. This expresses the efficiency and economic value of the microblade production system. The flexible use of pressure microblades identified at Swan Point CZ4b is also found in Japan, Korea, Kamchatka, and the North Baikal region, suggesting that their modes of use accompany the spread of early microblade pressure knapping over an immense territory across Beringia.

Through Time: Reconstructing Palaeolithic Occupations Through Use-Wear Analysis in the Middle Palaeolithic Site of Ciota Ciara (Borgosesia, Italy)

Lithic use-wear analysis, through defining site function and allowing reconstructing of patterns of human occupation, can contribute to our understanding of archaeological palimpsests. The Ciota Ciara cave represents an excellent case study for this methodology. Multidisciplinary research so far conducted on the materials recovered from the atrial sector of the cave distinguishes three archaeological units from a Middle Palaeolithic occupation of the site: stratigraphic units (SUs) 13, 14, and 15. Each unit is interpreted as referring to a period of numerous, superimposed episodes of human occupation, the characteristics of which we try to reconstruct and present in this work through use-wear studies. The functional analysis of lithic industries from the upper units (13 and 14) has already been published previously; here, we report corresponding new data from the lowest level, SU 15. By comparing the use-wear results from the three units and integrating the findings with data from the geoarchaeological, palaeontological, zooarchaeological, and technological studies, we attempt to reconstruct the different phases of human occupation represented in the site through time, contributing to current interpretations regarding settlement dynamics and human behaviour in the Middle Palaeolithic of north-western Italy.

South Cuidrach

A new site in north Skye has revealed evidence of human occupation from the Late Upper Palaeolithic as well as the Early and Late Mesolithic periods, suggesting repeated visits by humans for at least 5,000 years from the Late Glacial Interstadial through the Loch Lomond Readvance and up to the mid-Holocene, a time of dynamic climatic and sea-level change. South Cuidrach is one of several sites in the north of the Isle of Skye and around the Inner Sound with lithic (stone tool) evidence diagnostic of a human presence before the mid-Holocene. These sites currently represent a unique concentration of pre-Late Mesolithic sites in Scotland. The lithic evidence which forms the backbone of the cultural and temporal characterisation of the site at South Cuidrach is outlined here. This includes characteristic points and microliths, burins, cores and other items diagnostic of specific cultural groups. Additionally, it has become evident that Rum bloodstone, a raw material well known from the Late Mesolithic period in the region, may be absent before the Early/Late Mesolithic transition, with baked mudstone from Staffin in North Skye being the primary raw material used before this time. The need for detailed knowledge of the region’s lithic technology and typology is well illustrated here, as small details frequently reflect important chronological differences.

Urban occupation and surface runoff in cities: a study case in Piracicaba - SP

This study analyzes how uncontrolled human occupation can negatively impact surface runoff conditions in urban environments. For this purpose, the study assesses the correlation between rainfall, Piracicaba River flow and the urban occupation growth regarding the incidence of floods in Piracicaba-SP. To address the research question: Is the increase in flooding caused by the increased population density? The following data was used: flow and precipitation data in the urban perimeter, obtained from the Piracicaba Water and Electricity Department; population and density data from five neighborhoods based on the "Google Earth Pro" software, covering sixteen years of study. The findings indicate that three districts experienced increased flooding, while two other well-established districts did not encounter significant changes in flood frequency. 

Reevaluating the “elephant butchery area” at the Middle Pleistocene site of Notarchirico (MIS 16) (Venosa Basin, Basilicata, Italy)

The archaeological site of Notarchirico, chronologically placed at the end of MIS 17 and MIS 16 (675-610 ka), is a key site for studying Acheulean technology in southern Europe and gaining a better understanding of human occupation in that region during the Middle Pleistocene. It was excavated between 1979 and 1995 by Marcello Piperno and re-opened since 2016. Between 1990 and 1991, around forty remains of Palaeloxodon antiquus, mostly comprising the head of the animal, such as cranium, mandible and tusks fragments belonging to a sub-adult male were discovered as a result of the excavation of a lateral discontinuity of the level A, situated in an area known as the “elephant butchery area”. Remains of deer, mainly assigned to Dama sp., and 42 stone tools, including choppers, hand-axes, cores and some flakes were also identified in the surroundings. This accumulation was originally interpreted as a butchering site, reflecting a single event of processing of an elephant carcass, and the entire paleosurface was exposed to visitors in situ. This work re-evaluates the original archaeological materials, especially those still preserved on the paleosurface, in terms of stratigraphic distribution, taphonomy and technology, to critically evaluate the putative role of hominins in the exploitation of the megaherbivore. After a meticulous examination of each element's surface and its deposition, we conclude that there is no support for the previous interpretation of the so-called "elephant butchery area" of Notarchirico as the result a butchery event, as there is no evidence of human exploitation of the remains and the accumulation derives from at least two diverse and unrelated depositional events, one resulting in the deposition of the elephant remains, and the other of the majority of the fallow deer remains and the stone tools.

Raw-material exploitation in the Earlier and Middle Stone Age in the Eastern Desert of Egypt: evidence from Wadi Abu Subeira

Abstract Despite its key role in out-of-Africa hominin dispersals, little is known about Pleistocene human occupation of north-eastern Africa outside the Nile Valley and desert oases. A survey in Wadi Abu Subeira aims to help fill this gap and attests to the repeated occupation of the Eastern Desert during the Pleistocene.

Influence of Human Activities and Occupancy on the Emission of Indoor Particles from Respiratory and Nonrespiratory Sources

Influence of Human Activities and Occupancy on the Emission of Indoor Particles from Respiratory and Nonrespiratory Sources

The Persian plateau served as hub for Homo sapiens after the main out of Africa dispersal

A combination of evidence, based on genetic, fossil and archaeological findings, indicates that Homo sapiens spread out of Africa between ~70-60 thousand years ago (kya). However, it appears that once outside of Africa, human populations did not expand across all of Eurasia until ~45 kya. The geographic whereabouts of these early settlers in the timeframe between ~70-60 to 45 kya has been difficult to reconcile. Here we combine genetic evidence and palaeoecological models to infer the geographic location that acted as the Hub for our species during the early phases of colonisation of Eurasia. Leveraging on available genomic evidence we show that populations from the Persian Plateau carry an ancestry component that closely matches the population that settled the Hub outside Africa. With the paleoclimatic data available to date, we built ecological models showing that the Persian Plateau was suitable for human occupation and that it could sustain a larger population compared to other West Asian regions, strengthening this claim.

ESR/U-series and pIR-IR290 dating of the Middle Pleistocene site of Lunel-Viel (LV I), Hérault, Southern France

The Mas des Caves site at Lunel-Viel, Southern France, is a complex of several caves, developed in Miocene limestone, that have yielded a rich archaeo-palaeontological sequence attributed to the Middle Pleistocene with abundant vertebrates and lithic artefacts. The first caves (LVI, II and III), discovered in 1800, were excavated at the beginning of the 19th century (Serres et al., 1828) before falling into oblivion for over a century. The main cavity is LVI, when LVII and III are smaller subparallel galleries not connected to LVI. In the early 1970s, research was conducted in the main gallery by E. Bonifay who discovered an extension named LVIV and the natural entrance (sinkhole, doline) both completely closed now.Recently, a multidisciplinary approach has been set up (DRAC-SRA Occitanie) to contextualize the ancient collections with the recent ones and to allow a better understanding of the site formation, palaeoenvironmental and behavioral history of the animals and humans who lived there (Brugal et al., 2021). The previous chronology based on faunal evidence yields important biomarkers (including new genus and species/subspecies) making Lunel-Viel a major Middle Pleistocene site in the European record. Among various dating techniques used in this study, trapped-charged methods such as combined ESR/U-series and pIR-IR290 were applied on fossil tooth enamel and on K-feldspars, respectively. The results obtained by both methods are in agreement and suggest a period of human occupation between 300 and 200 ka. This age range matches well with the composition of the faunal assemblage attributed to the second part of the Middle Pleistocene (biochronology) and which constrains the occupation to a cool/temperate and humid period which could be contemporaneous with the MIS7 (Lisiecki and Raymo, 2005).

Purpose in Life as an Explicit Outcome of Occupational Therapy.

Purpose in life is increasingly understood to be important to health and well-being. Despite occupational therapy's long history of using occupations to advance health and the linkage between a subclass of occupations and purpose in life, the term is nearly absent from the American Occupational Therapy Association's documents and the profession's empirical literature. We propose that the profession explicitly name purpose in life as among our intervention outcomes and address disruptions of purpose in life in practice. This can be accomplished by first investing in purpose in our own lives, discussing the topic with colleagues and students, identifying possible purpose disruptions in our clients, and using direct or indirect intervention approaches to help clients reconnect to purpose in their lives. By explicitly naming purpose in life as part of the domain of occupational therapy, we become poised to leverage human occupation to address both a broad societal gap and our clients' needs for a renewal of purpose in life.

Preclinical and translational pharmacology of afucosylated anti-CCR8 antibody for depletion of tumour-infiltrating regulatory T cells.

RO7502175 is an afucosylated antibody designed to eliminate C-C motif chemokine receptor 8 (CCR8)+ Treg cells in the tumour microenvironment through enhanced antibody-dependent cellular cytotoxicity (ADCC). We report findings from preclinical studies characterizing pharmacology, pharmacokinetics (PK)/pharmacodynamics (PD) and safety profile of RO7502175 and discuss the translational PK/PD approach used to inform first-in-human (FiH) dosing strategy and clinical development in solid tumour indications. RO7502175 demonstrated selective ADCC against human CCR8+ Treg cells from dissociated tumours in vitro. In cynomolgus monkeys, RO7502175 exhibited a biphasic concentration-time profile consistent with immunoglobulin G1 (IgG1) antibodies, reduced CCR8+ Treg cells in the blood, induced minimal and transient cytokine secretion, and was well tolerated with a no-observed-adverse-effect level (NOAEL) of 100 mg·kg-1 . Moreover, RO7502175 caused minimal cytokine release from peripheral blood mononuclear cells (PBMCs) in vitro. A quantitative model was developed to capture surrogate anti-murine CCR8 antibody PK/PD and tumour dynamics in mice and RO7502175 PK/PD in cynomolgus monkeys. Subsequently, the model was used to project RO7502175 human PK and receptor occupancy (RO) in patients. Because traditional approaches resulted in a low FiH dose for this molecule, even with its superior preclinical safety profile, an integrated approach based on the totality of preclinical data and modelling insights was used for starting dose selection. This work demonstrates a translational research strategy for collecting and utilizing relevant nonclinical data, developing a mechanistic PK/PD model and using a comprehensive approach to inform clinical study design for RO7502175.