Competing risk analysis of cardiovascular disease risk in breast cancer patients receiving a radiation boost.

BACKGROUND: Thoracic radiotherapy may damage the myocardium and arteries, increasing cardiovascular disease (CVD) risk. Women with a high local breast cancer (BC) recurrence risk may receive an additional radiation boost to the tumor bed. OBJECTIVE: We aimed to evaluate the CVD risk and specifically ischemic heart disease (IHD) in BC patients treated with a radiation boost, and investigated whether this was modified by age. METHODS: We identified 5260 BC patients receiving radiotherapy between 2005 and 2016 without a history of CVD. Boost data were derived from hospital records and the national cancer registry. Follow-up data on CVD events were obtained from Statistics Netherlands until December 31, 2018. The relation between CVD and boost was evaluated with competing risk survival analysis. RESULTS: 1917 (36.4%) received a boost. Mean follow-up was 80.3 months (SD37.1) and the mean age 57.8 years (SD10.7). Interaction between boost and age was observed for IHD: a boost was significantly associated with IHD incidence in patients younger than 40 years but not in patients over 40 years. The subdistribution hazard ratio (sHR) was calculated for ages from 25 to 75 years, showing a sHR range from 5.1 (95%CI 1.2-22.6) for 25-year old patients to sHR 0.5 (95%CI 0.2-1.02) for 75-year old patients. CONCLUSION: In patients younger than 40, a radiation boost is significantly associated with an increased risk of CVD. In absolute terms, the increased risk was low. In older patients, there was no association between boost and CVD risk, which is likely a reflection of appropriate patient selection.

A long-term study of size variation in Northern Goshawk Accipiter gentilis across Scandinavia, with a focus on Norway.

Changing climate and growing human impacts are resulting in globally rising temperatures and the widespread loss of habitats. How species will adapt to these changes is not well understood. The Northern Goshawk (Accipiter gentilis) can be found across the Holarctic but is coming under more intense pressure in many places. Studies of recent populations in Finland and Denmark have shown a marked decline in body size of Northern Goshawks over the past century. Here we investigate long-term changes to Norwegian populations of Northern Goshawk by including material from the Middle Ages. We measured 240 skeletons of modern Northern Goshawks from Norway, Sweden, Denmark and Finland, and 89 Medieval Goshawk bones. Our results show that Norwegian and Swedish female Goshawks have decreased in size over the past century, whilst males showed little decline. Medieval female Goshawks were larger than contemporary females. A decline in forest habitats and a concomitant shift towards smaller prey likely drove a shift to smaller body size in Northern Goshawks. Our study shows that significant body size changes in birds can occur over relatively short time spans in response to environmental factors, and that these effects can sometimes differ between sexes.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial-a study protocol.

BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Future steps in cardio-oncology-a national multidisciplinary survey among healthcare professionals in the Netherlands.

BACKGROUND: The awareness of cancer therapy-related adverse cardiac effects is fueled by recent literature on cardiotoxicity incidence and detection strategies. Although this influences the sense of urgency, in current practice, cardiotoxicity monitoring and treatment is not structurally performed. With this study, we aimed to evaluate current perspectives on cardio-oncology and to assess needs, ultimately to determine an agenda for improvements in current practice. MATERIAL AND METHODS: A national multidisciplinary 36-question survey was conducted. The survey was developed by a multidisciplinary team, theoretically based on an implementation checklist and distributed by email, through cardiology and oncology societies as well as social media. RESULTS: One hundred ninety professionals completed the survey, of which 66 were cardiologists, 66 radiation oncologists, and 58 medical oncologists and hematologists. Many professionals were unaware of their specialisms' cardio-oncology guidelines: 62.1% of cardiologists and 29.3% of the hematologists and medical oncologists respectively. Many cardiologists (N = 46; 69.7%), radiation oncologists (N = 45; 68.2%), and hematologists and medical oncologists (N = 38; 65.5%) expressed that they did not have sufficient knowledge to treat cardio-oncology patients and would either refer a patient or aspire to gain more knowledge on the topic. CONCLUSION: The field of cardio-oncology is advancing rapidly, with progress in stratification and detection strategies leading to the development of new guidelines and consensus statements. However, the application of these guidelines in current practice appears to be lagging. Professionals express a need for additional training and a practical guideline including risk stratification, monitoring, and treatment strategies. Multidisciplinary discussion and consensus on cardio-oncology care is vital to improve implementation of cardio-oncology guidelines, ultimately to improve cardiac care for oncology patients.

More bones of Leptoptilos robustus from Flores reveal new insights into giant marabou stork paleobiology and biogeography.

Liang Bua (Flores, Indonesia) has yielded remains of a faunal community that included small-bodied and small-brained hominins, dwarf proboscideans, Komodo dragons, vultures and giant marabou storks (Leptoptilos robustus). Previous research suggested that L. robustus evolved from a smaller L eptoptilos dubius-like Middle Pleistocene ancestor and may have been flightless. However, analyses of this species' considerably expanded hypodigm (n = 43, MNI = 5), which includes 21 newly discovered bones described here for the first time, reveals that the wing bones of L. robustus were well-developed and this species was almost certainly capable of active flight. Moreover, L. robustus bones are broadly similar to Leptoptilos falconeri remains from sites in Africa and Eurasia, and its overall size range is comparable to fossils attributed to L. falconeri and similar specimens, as well as those of Leptoptilos lüi (China) and Leptoptilos titan (Java). This suggests that a Pleistocene dispersal of L. falconeri into Island Southeast Asia may have given rise to populations of giant marabou storks in this region. As L. robustus and L. titan are the most recent known representatives of these once plentiful giant marabou storks, Island Southeast Asia likely acted as a refugium for the last surviving members of this lineage.

Global raster dataset on historical coastline positions and shelf sea extents since the Last Glacial Maximum.

Motivation: Historical changes in sea level caused shifting coastlines that affected the distribution and evolution of marine and terrestrial biota. At the onset of the Last Glacial Maximum (LGM) 26 ka, sea levels were >130 m lower than at present, resulting in seaward-shifted coastlines and shallow shelf seas, with emerging land bridges leading to the isolation of marine biota and the connection of land-bridge islands to the continents. At the end of the last ice age, sea levels started to rise at unprecedented rates, leading to coastal retreat, drowning of land bridges and contraction of island areas. Although a growing number of studies take historical coastline dynamics into consideration, they are mostly based on past global sea-level stands and present-day water depths and neglect the influence of global geophysical changes on historical coastline positions. Here, we present a novel geophysically corrected global historical coastline position raster for the period from 26 ka to the present. This coastline raster allows, for the first time, calculation of global and regional coastline retreat rates and land loss rates. Additionally, we produced, per time step, 53 shelf sea rasters to present shelf sea positions and to calculate the shelf sea expansion rates. These metrics are essential to assess the role of isolation and connectivity in shaping marine and insular biodiversity patterns and evolutionary signatures within species and species assemblages. Main types of variables contained: The coastline age raster contains cells with ages in thousands of years before present (bp), representing the time since the coastline was positioned in the raster cells, for the period between 26 ka and the present. A total of 53 shelf sea rasters (sea levels <140 m) are presented, showing the extent of land (1), shelf sea (0) and deep sea (NULL) per time step of 0.5 kyr from 26 ka to the present. Spatial location and grain: The coastline age raster and shelf sea rasters have a global representation. The spatial resolution is scaled to 120 arcsec (0.333° × 0.333°), implying cells of c. 3,704 m around the equator, 3,207 m around the tropics (±30°) and 1,853 m in the temperate zone (±60°). Time period and temporal resolution: The coastline age raster shows the age of coastline positions since the onset of the LGM 26 ka, with time steps of 0.5 kyr. The 53 shelf sea rasters show, for each time step of 0.5 kyr, the position of the shelf seas (seas shallower than 140 m) and the extent of land. Level of measurement: Both the coastline age raster and the 53 shelf sea rasters are provided as TIFF files with spatial reference system WGS84 (SRID 4326). The values of the coastline age raster per grid cell correspond to the most recent coastline position (in steps of 0.5 kyr). Values range from 0 (0 ka, i.e., present day) to 260 (26 ka) in bins of 5 (0.5 kyr). A value of "no data" is ascribed to pixels that have remained below sea level since 26 ka. Software format: All data processing was done using the R programming language.

Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer.

IMPORTANCE: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. OBJECTIVE: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter cohort study of 15 915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. EXPOSURES: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). MAIN OUTCOMES AND MEASURES: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. RESULTS: Of the 15 915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15 879 (99.8%) were women. Seventy percent (n = 11 179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). CONCLUSIONS AND RELEVANCE: This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03206333.

No evidence for widespread island extinctions after Pleistocene hominin arrival.

The arrival of modern humans into previously unoccupied island ecosystems is closely linked to widespread extinction, and a key reason cited for Pleistocene megafauna extinction is anthropogenic overhunting. A common assumption based on late Holocene records is that humans always negatively impact insular biotas, which requires an extrapolation of recent human behavior and technology into the archaeological past. Hominins have been on islands since at least the early Pleistocene and Homo sapiens for at least 50 thousand y (ka). Over such lengthy intervals it is scarcely surprising that significant evolutionary, behavioral, and cultural changes occurred. However, the deep-time link between human arrival and island extinctions has never been explored globally. Here, we examine archaeological and paleontological records of all Pleistocene islands with a documented hominin presence to examine whether humans have always been destructive agents. We show that extinctions at a global level cannot be associated with Pleistocene hominin arrival based on current data and are difficult to disentangle from records of environmental change. It is not until the Holocene that large-scale changes in technology, dispersal, demography, and human behavior visibly affect island ecosystems. The extinction acceleration we are currently experiencing is thus not inherent but rather part of a more recent cultural complex.

MR-Guided Adaptive Radiotherapy for Bladder Cancer.

Radiotherapy has an important role in the curative and palliative treatment settings for bladder cancer. As a target for radiotherapy the bladder presents a number of technical challenges. These include poor tumor visualization and the variability in bladder size and position both between and during treatment delivery. Evidence favors the use of magnetic resonance imaging (MRI) as an important means of tumor visualization and local staging. The availability of hybrid systems incorporating both MRI scanning capabilities with the linear accelerator (MR-Linac) offers opportunity for in-room and real-time MRI scanning with ability of plan adaption at each fraction while the patient is on the treatment couch. This has a number of potential advantages for bladder cancer patients. In this article, we examine the technical challenges of bladder radiotherapy and explore how magnetic resonance (MR) guided radiotherapy (MRgRT) could be leveraged with the aim of improving bladder cancer patient outcomes. However, before routine clinical implementation robust evidence base to establish whether MRgRT translates into improved patient outcomes should be ascertained.

Size variation in mid-Holocene North Atlantic Puffins indicates a dynamic response to climate change.

Seabirds are one of the most at-risk groups, with many species in decline. In Scandinavia, seabirds are at a heightened risk of extinction due to accelerated global warming. Norway is home to significant portion of the European Atlantic Puffin (Fratercula arctica) populations, but Norwegian populations have declined significantly during the last decades. In this paper we use biometric data from modern and archaeological F. arctica specimens to investigate patterns in body size variation over time of this iconic species. We aimed to set out a baseline for our archaeological comparison by firstly investigating whether modern subspecies of F. arctica are reflected in the osteological characters and are enough to distinguish subspecies from the bones alone. We then investigated if archaeological remains of F. arctica differ in size from the modern subspecies. Our results show that the subspecies Fratercula arctica naumanni was distinctly larger than the other subspecies. However, Fratercula arctica arctica and Fratercula arctica grabae were difficult to separate based on size. This generally supports ornithological observations. Post-Medieval F. arctica bones from Måsøy were similar to modern F. a. arctica populations. The mid-Holocene remains from Dollsteinhola overlaps with the modern size ranges of F. a. arctica and F. a. grabae but are generally shorter and more robust. Dollsteinhola is located close to the borders of the modern breeding ranges of both F. a. arctica and F. a. grabae. We consider it therefore likely that given the mid-Holocene climatic oscillations, breeding ranges of the two subspecies shifted north or south accordingly. However, this does not explain the different proportions of the Dollsteinhola specimens. Our data provide the first evidence for shifting distributions in ancient Atlantic Puffins and represent the first osteological analysis of Fratercula arctica subspecies.

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer.

INTRODUCTION: Cardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECG-triggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called 'cardiovascular calcifications') measured automatically on planning CT scans of patients with breast cancer and CVD risk. METHODS AND ANALYSIS: In a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600). ETHICS AND DISSEMINATION: The Institutional Review Boards of the participating hospitals decided that the Medical Research Involving Human Subjects Act does not apply. Findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT03206333.

The spatio-temporal distribution of archaeological and faunal finds at Liang Bua (Flores, Indonesia) in light of the revised chronology for Homo floresiensis.

Liang Bua, the type site of Homo floresiensis, is a limestone cave on the Indonesian island of Flores with sedimentary deposits currently known to range in age from about 190 thousand years (ka) ago to the present. Recent revision of the stratigraphy and chronology of this depositional sequence suggests that skeletal remains of H. floresiensis are between ∼100 and 60 ka old, while cultural evidence of this taxon occurs until ∼50 ka ago. Here we examine the compositions of the faunal communities and stone artifacts, by broad taxonomic groups and raw materials, throughout the ∼190 ka time interval preserved in the sequence. Major shifts are observed in both the faunal and stone artifact assemblages that reflect marked changes in paleoecology and hominin behavior, respectively. Our results suggest that H. floresiensis and Stegodon florensis insularis, along with giant marabou stork (Leptoptilos robustus) and vulture (Trigonoceps sp.), were likely extinct by ∼50 ka ago. Moreover, an abrupt and statistically significant shift in raw material preference due to an increased use of chert occurs ∼46 thousand calibrated radiocarbon (14C) years before present (ka cal. BP), a pattern that continues through the subsequent stratigraphic sequence. If an increased preference for chert does, in fact, characterize Homo sapiens assemblages at Liang Bua, as previous studies have suggested (e.g., Moore et al., 2009), then the shift observed here suggests that modern humans arrived on Flores by ∼46 ka cal. BP, which would be the earliest cultural evidence of modern humans in Indonesia.

Environmental dynamics during the onset of the Middle Stone Age in eastern Africa.

Development of the African Middle Stone Age (MSA) before 300,000 years ago raises the question of how environmental change influenced the evolution of behaviors characteristic of early Homo sapiens We used temporally well-constrained sedimentological and paleoenvironmental data to investigate environmental dynamics before and after the appearance of the early MSA in the Olorgesailie basin, Kenya. In contrast to the Acheulean archeological record in the same basin, MSA sites are associated with a markedly different faunal community, more pronounced erosion-deposition cycles, tectonic activity, and enhanced wet-dry variability. Aspects of Acheulean technology in this region imply that, as early as 615,000 years ago, greater stone material selectivity and wider resource procurement coincided with an increased pace of land-lake fluctuation, potentially anticipating the adaptability of MSA hominins.

Late Pleistocene songbirds of Liang Bua (Flores, Indonesia); the first fossil passerine fauna described from Wallacea.

BACKGROUND: Passerines (Aves: Passeriformes) dominate modern terrestrial bird communities yet their fossil record is limited. Liang Bua is a large cave on the Indonesian island of Flores that preserves Late Pleistocene-Holocene deposits (∼190 ka to present day). Birds are the most diverse faunal group at Liang Bua and are present throughout the stratigraphic sequence. METHODS: We examined avian remains from the Late Pleistocene deposits of Sector XII, a 2 נ2 m area excavated to about 8.5 m depth. Although postcranial passerine remains are typically challenging to identify, we found several humeral characters particularly useful in discriminating between groups, and identified 89 skeletal elements of passerines. RESULTS: At least eight species from eight families are represented, including the Large-billed Crow (Corvus cf. macrorhynchos), the Australasian Bushlark (Mirafra javanica), a friarbird (Philemon sp.), and the Pechora Pipit (Anthus cf. gustavi). DISCUSSION: These remains constitute the first sample of fossil passerines described in Wallacea. Two of the taxa no longer occur on Flores today; a large sturnid (cf. Acridotheres) and a grassbird (Megalurus sp.). Palaeoecologically, the songbird assemblage suggests open grassland and tall forests, which is consistent with conditions inferred from the non-passerine fauna at the site. Corvus cf. macrorhynchos, found in the Homo floresiensis-bearing layers, was likely part of a scavenging guild that fed on carcasses of Stegodon florensis insularis alongside vultures (Trigonoceps sp.), giant storks (Leptoptilos robustus), komodo dragons (Varanus komodoensis), and probably H. floresiensis as well.

The extreme insular adaptation of Garganornis ballmanni Meijer, 2014: a giant Anseriformes of the Neogene of the Mediterranean Basin.

New skeletal elements of the recently described endemic giant anseriform Garganornis ballmanni Meijer, 2014 are presented, coming from the type-area of the Gargano and from Scontrone, southern and central Italy, respectively. The new remains represent the first bird remains found at Scontrone so far, and another shared element between these two localities, both part of the Apulia-Abruzzi Palaeobioprovince. The presence of a very reduced carpometacarpus confirms its flightlessness, only previously supposed on the basis of the very large size, while the morphologies of tarsometatarsus and posterior phalanges clearly indicate the adaptation of G. ballmanni to a terrestrial, non-aquatic, lifestyle. Its very large body size is similar to that observed in different, heavily modified, insular waterfowl and has been normally interpreted as the response to the absence of terrestrial predators and a protection from the aerial ones. The presence of a carpal knob in the proximal carpometacarpus also indicates a fighting behaviour for this large terrestrial bird species.

Intranodal signal suppression in pelvic MR lymphography of prostate cancer patients: a quantitative comparison of ferumoxtran-10 and ferumoxytol.

OBJECTIVES: The key to MR lymphography is suppression of T2* MR signal in normal lymph nodes, while retaining high signal in metastatic nodes. Our objective is to quantitatively compare the ability of ferumoxtran-10 and ferumoxytol to suppress the MR signal in normal pelvic lymph nodes. METHODS: In 2010, a set of consecutive patients who underwent intravenous MR Lymphography (MRL) were included. Signal suppression in normal lymph nodes in T2*-weighted images due to uptake of USPIO (Ultra-Small Superparamagnetic Particles of Iron Oxide) was quantified. Signal suppression by two USPIO contrast agents, ferumoxtran-10 and ferumoxytol was compared using Wilcoxon's signed rank test. RESULTS: Forty-four patients were included, of which all 44 had a ferumoxtran-10 MRL and 4 had additionally a ferumoxytol MRL. A total of 684 lymph nodes were identified in the images, of which 174 had been diagnosed as metastatic. USPIO-induced signal suppression in normal lymph nodes was significantly stronger in ferumoxtran-10 MRL than in ferumoxytol MRL (p < 0.005). CONCLUSIONS: T2* signal suppression in normal pelvic lymph nodes is significantly stronger with ferumoxtran-10 than with ferumoxytol, which may affect diagnostic accuracy.

Age and context of the oldest known hominin fossils from Flores.

Recent excavations at the early Middle Pleistocene site of Mata Menge in the So'a Basin of central Flores, Indonesia, have yielded hominin fossils attributed to a population ancestral to Late Pleistocene Homo floresiensis. Here we describe the age and context of the Mata Menge hominin specimens and associated archaeological findings. The fluvial sandstone layer from which the in situ fossils were excavated in 2014 was deposited in a small valley stream around 700 thousand years ago, as indicated by (40)Ar/(39)Ar and fission track dates on stratigraphically bracketing volcanic ash and pyroclastic density current deposits, in combination with coupled uranium-series and electron spin resonance dating of fossil teeth. Palaeoenvironmental data indicate a relatively dry climate in the So'a Basin during the early Middle Pleistocene, while various lines of evidence suggest the hominins inhabited a savannah-like open grassland habitat with a wetland component. The hominin fossils occur alongside the remains of an insular fauna and a simple stone technology that is markedly similar to that associated with Late Pleistocene H. floresiensis.

Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia.

Homo floresiensis, a primitive hominin species discovered in Late Pleistocene sediments at Liang Bua (Flores, Indonesia), has generated wide interest and scientific debate. A major reason this taxon is controversial is because the H. floresiensis-bearing deposits, which include associated stone artefacts and remains of other extinct endemic fauna, were dated to between about 95 and 12 thousand calendar years (kyr) ago. These ages suggested that H. floresiensis survived until long after modern humans reached Australia by ~50 kyr ago. Here we report new stratigraphic and chronological evidence from Liang Bua that does not support the ages inferred previously for the H. floresiensis holotype (LB1), ~18 thousand calibrated radiocarbon years before present (kyr cal. BP), or the time of last appearance of this species (about 17 or 13-11 kyr cal. BP). Instead, the skeletal remains of H. floresiensis and the deposits containing them are dated to between about 100 and 60 kyr ago, whereas stone artefacts attributable to this species range from about 190 to 50 kyr in age. Whether H. floresiensis survived after 50 kyr ago--potentially encountering modern humans on Flores or other hominins dispersing through southeast Asia, such as Denisovans--is an open question.

The avian fossil record in Insular Southeast Asia and its implications for avian biogeography and palaeoecology.

Excavations and studies of existing collections during the last decades have significantly increased the abundance as well as the diversity of the avian fossil record for Insular Southeast Asia. The avian fossil record covers the Eocene through the Holocene, with the majority of bird fossils Pleistocene in age. Fossil bird skeletal remains represent at least 63 species in 54 genera and 27 families, and two ichnospecies are represented by fossil footprints. Birds of prey, owls and swiftlets are common elements. Extinctions seem to have been few, suggesting continuity of avian lineages since at least the Late Pleistocene, although some shifts in species ranges have occurred in response to climatic change. Similarities between the Late Pleistocene avifaunas of Flores and Java suggest a dispersal route across southern Sundaland. Late Pleistocene assemblages of Niah Cave (Borneo) and Liang Bua (Flores) support the rainforest refugium hypothesis in Southeast Asia as they indicate the persistence of forest cover, at least locally, throughout the Late Pleistocene and Holocene.