Michael Fradley

Carfilzomib is highly effective in the treatment of multiple myeloma, but it has been associated with cardiovascular adverse events that impact patient outcomes. Our prior global metabolomic analyses indicated an association between hydrophilic bile acids and carfilzomib‐cardiotoxicity risk, although a causal relationship remained to be determined. Here, our objective was to validate the previously identified bile acids in an independent cohort and investigate whether these hydrophilic bile acids play a causal role in carfilzomib‐cardiotoxicity using Mendelian randomization. Using targeted metabolomics, we validated the association between glycoursodeoxycholic acid and carfilzomib‐cardiotoxicity in an independent cohort ( n = 61). We then performed two‐sample Mendelian randomization analyses, using metabolome‐wide association study results to provide the genetic instruments for bile acid levels as exposure and genome‐wide association study summary statistics from the UK Biobank ( n = 484,598) as the outcome data for cardiovascular adverse events. Causal inference was assessed with the inverse‐variance weighted method, followed by multiple sensitivity analyses. Higher glycoursodeoxycholic acid concentration (odds ratio = 0.34, P = 0.032) was associated with lower cardiotoxicity risk after adjusting for hypertension and high levels of brain natriuretic peptides. Mendelian randomization analysis demonstrated a robust causal effect of glycoursodeoxycholic acid on cardiotoxicity risk (β = −0.00065, P = 6.2 × 10 ⁻⁵ ). Gene enrichment analysis indicated pathways involving potassium channel regulation and thromboxane signaling to be implicated. This integrative metabolomic and genetic investigation supports a potential protective role of glycoursodeoxycholic acid in cardiovascular vulnerability and motivates larger, carfilzomib‐specific studies to evaluate its utility for risk stratification.

Analysis of historic aerial photography has identified a possible monumental formal garden complex on the outskirts of Tabriz, Iran. Here, the authors describe this complex and explain why it is an important addition to our knowledge of elite Persian garden design practice that spread globally over time.

The marginal arid region encompassing the western Nafud in the east to Wadi Tabuk in the west has only been subject to limited archaeological survey. This paper reports on data from a systematic remote sensing survey of the region as part of the Endangered Archaeology in the Middle East and North Africa project, using the results to produce preliminary models of settlement, occupation, and land-use, and contextualising within the broader archaeological landscapes of northern Arabia. It also provides datasets that can be used to outline broad trends in modern disturbances and threats to these sites, in part demonstrating the effectiveness of this approach for producing a cost-effective baseline dataset for the management of heritage sites at a landscape level. While confirming that long-term settlement and agriculture were largely confined to the Wadi Tabuk region from the later prehistoric period onwards, including the identification of a significant new fortified settlement south of Tabuk, it also demonstrates evidence of a broader complex landscape of pastoralism, funerary monuments, and other monumental structures across much of the survey area. Most notably, this area may mark a border zone when geographically distinct distributions of Neolithic-adjacent kites and mustatil meet with minimal overlap.

Remote sensing survey in southern Jordan has identified at least three Roman temporary camps that indicate a probable undocumented military campaign into what is today Saudi Arabia, and which we conjecture is linked to the Roman annexation of the Nabataean kingdom in AD 106.

The historic environment of north-west Saudi Arabia is likely to be severely impacted by the construction of the Neom mega-city complex and the development of the city’s hinterland. This region, located east of the Gulf of Aqaba, has only been subject to limited archaeological survey in the past, limiting any assessment of this negative impact. This paper presents data collected through a remote sensing survey of the region undertaken by the Endangered Archaeology in the Middle East and North Africa (EAMENA) project, independent of the Neom project. It is argued that this data reflects a landscape of movement between north and south, with evidence of structures and monuments from at least the Bronze Age through to the pre-Islamic period, but little evidence of permanent settlement or agriculture. This should not be dismissed as a peripheral landscape, but one that contains rich archaeological evidence of concentrated activity, suggesting that some areas have held long-term significance to the people inhabiting and moving through this region.

Remote-sensing analysis of open-source satellite imagery has identified a major, new distribution of undocumented hunting kite structures in northern Arabia. This new data has important implications on the environmental viability of hunting and on possible settlement patterns during the early and middle Holocene. Running across the eastern side of the Nafud Desert in Saudi Arabia, this research has identified star-shaped kites in a distribution that continues on to southern Iraq. From a broader perspective, this new distribution appears to represent a continuation of the well-known arc of kites recorded running principally through southern Syria and eastern Jordan. As well as representing an important archaeological identification in its own right, this new distribution also has important implications in terms of the paleoenvironment of the region, faunal dispersals and human cultural connections.

As a result of its geographic location, cultural diversity and historical trajectory, the Gaza strip is a key zone of scholarly enquiry and has a central role in the historical, social, political, economic, legislative and environmental discourses for the wider region. Existing historical knowledge of Gaza is dominated by combative narrative trends that emphasise the events of the 20th and 21st centuries and invoke archaeology extensively. In this context, cycles of material preservation and damage—often accompanying other forms of violence—have attracted the attention of academics and international media. Among the corollaries of this situation, is the destruction and marginalisation of vulnerable cultural heritage, particularly maritime cultural heritage, which is subjected to additional environmental, climatic, and anthropogenic pressures. As a means of countering the challenges on current field research in the region and to further assess the damage and threats faced by archaeological fabric, this paper combines data from coastal and archaeological research conducted in the Gaza Strip to create a benchmark for the study of its maritime archaeology. Additional information on the alteration of coastal landscape is deduced through the analysis of aerial photographs and satellite imagery. This study falls within the scope of the Maritime Endangered Archaeology in the Middle East and Africa Project (MarEA). MarEA aims to comprehensively document and assess vulnerable maritime archaeology (underwater, nearshore, coastal) and produce baseline information that can enhance existing infrastructure on archaeological monitoring and management.

The Endangered Archaeology in the Middle East and North Africa (EAMENA) project (www.eamena.org) is among the most ambitious archaeological documentation projects ever to have taken place across th...

This paper presents a study of the rich archaeological landscape of the Jericho Oasis, drawing on historical aerial photography and more recent satellite imagery to survey this cultural landscape and assess issues affecting its preservation over the past century. The timing of the paper is pertinent as non-U.S. satellite companies have recently begun to produce higher resolution satellite imagery of Israel and the Occupied Palestinian Territories (OPT), and restrictions on imagery resolution in the U.S. have been lowered as a result of research by the EAMENA project. Whilst increasingly widespread availability of high-resolution satellite imagery and orthophotos can effectively support heritage monitoring in this heavily-developed region, this paper demonstrates that it is the use of historical aerial photography that has enabled the identification of a range of previously unrecognized archaeological features. These new data offer a first tentative step in revising our current understanding of the development of human settlement across the Jericho Oasis.

The use of aerial photography in the Middle East and North Africa region stretches back to the First World War. While historic aerial photography has continued to be utilized in research in the region, there has been only limited consideration of different photographic sources. This paper will focus on the use of aerial photography by British forces in the MENA region for photogrammetric mapping missions in the period from the First World War through to the start of the Second World War, when large areas were surveyed via the capture of overlapping vertical photographs. The discussion will cover the survival and archiving of these collections, as well as current issues of access, as well as their overall archaeological potential, particularly as an early source of earth-observation data, comparable to more recent satellite imagery archives.