Ancient trash mounds unravel urban collapse a century before the end of Byzantine hegemony in the southern Levant.

The historic event of the Late Antique Little Ice Age (LALIA) was recently identified in dozens of natural and geological climate proxies of the northern hemisphere. Although this climatic downturn was proposed as a major cause for pandemic and extensive societal upheavals in the sixth-seventh centuries CE, archaeological evidence for the magnitude of societal response to this event is sparse. This study uses ancient trash mounds as a type of proxy for identifying societal crisis in the urban domain, and employs multidisciplinary investigations to establish the terminal date of organized trash collection and high-level municipal functioning on a city-wide scale. Survey, excavation, sediment analysis, and geographic information system assessment of mound volume were conducted on a series of mounds surrounding the Byzantine urban settlement of Elusa in the Negev Desert. These reveal the massive collection and dumping of domestic and construction waste over time on the city edges. Carbon dating of charred seeds and charcoal fragments combined with ceramic analysis establish the end date of orchestrated trash removal near the mid-sixth century, coinciding closely with the beginning of the LALIA event and outbreak of the Justinian Plague in the year 541. This evidence for societal decline during the sixth century ties with other arguments for urban dysfunction across the Byzantine Levant at this time. We demonstrate the utility of trash mounds as sensitive proxies of social response and unravel the time-space dynamics of urban collapse, suggesting diminished resilience to rapid climate change in the frontier Negev region of the empire.

PLX-PAD Cell Treatment of Critical Limb Ischaemia: Rationale and Design of the PACE Trial.

BACKGROUND: Critical limb ischaemia (CLI) is a life threatening condition with a considerable risk of major amputation and death. Besides revascularisation, no treatment has been proven to reduce the risks. Therapeutic angiogenesis by gene or cell therapy has not demonstrated definitive evidence in randomised controlled trials. PLX-PAD is an "off the shelf" allogeneic placental derived, mesenchymal like cell therapy, which, in preclinical studies, has shown pro-angiogenic, anti-inflammatory, and regenerative properties. Favourable one year amputation free survival (AFS), and trends in reduction of pain scores and increase of tissue perfusion have been shown in two small, open label, phase I trials. METHODS: The PACE study is a phase III randomised, double blind, multicentre, multinational placebo controlled, parallel group study to evaluate the efficacy, tolerability, and safety of intramuscular injections of PLX-PAD cells to treat patients with atherosclerotic CLI with minor tissue loss (Rutherford Category 5) up to the ankle level, who are unsuitable for revascularisation or carry an unfavourable risk benefit for that treatment. The study will enroll 246 patients, who after screening are randomised in a ratio of 2:1 to treatment with intramuscular injections of PLX-PAD 300 × 106 cells or placebo on two occasions, eight weeks apart. The primary efficacy endpoint is time to major amputation or death (amputation free survival), which will be assessed in follow up of at least 12 months and up to 36 months. CONCLUSIONS: Based on favourable pre-clinical and initial clinical study results, the PACE phase III randomised controlled trial will evaluate placenta derived PLX-PAD cell treatment in patients with critical limb ischaemia, with an unfavourable risk benefit for revascularisation. Clinicaltrials.gov: NCT03006770.

Sodium MRI of a human transplanted kidney.

RATIONALE AND OBJECTIVES: Sodium magnetic resonance imaging (MRI) of the kidneys has been used to spatially map areas of sodium-concentrating activity and to quantify the corticomedullary sodium gradient in various physiologic and pathophysiologic conditions. In this case study, sodium MRI of a clinically well-functioning transplanted kidney was performed to determine whether its sodium gradient could be detected and quantified using this method. MATERIALS AND METHODS: Sodium MRI was performed on a 3T scanner with a commercial rectangular sodium surface coil placed on the lower abdomen over the palpable transplanted kidney. A three-dimensional gradient echo sequence, modified for multinuclear imaging, was applied to acquire (23)Na images. RESULTS: Five main renal pyramids within the medulla were detected, and the corticomedullary sodium gradient was quantified in each renal pyramid by both region of interest-based and pixel-by-pixel analyses, resulting in a mean medulla/cortex signal-to-noise ratio of 1.8 +/- 0.1 (n = 5) and a mean linear increase slope of 1.1 +/- 0.1 relative arbitrary units per mm (n = 5). CONCLUSIONS: The feasibility and usability of (23)Na MRI of a human renal allograft was demonstrated. Further studies are required to determine the clinical significance of this technique in the follow-up of patients after renal transplantation.

Recent advances in magnetic resonance neurospectroscopy.

Over the past two decades, proton magnetic resonance spectroscopy (proton MRS) of the brain has made the transition from research tool to a clinically useful modality. In this review, we first describe the localization methods currently used in MRS studies of the brain and discuss the technical and practical factors that determine the applicability of the methods to particular clinical studies. We also describe each of the resonances detected by localized solvent-suppressed proton MRS of the brain and discuss the metabolic and biochemical information that can be derived from an analysis of their concentrations. We discuss spectral quantitation and summarize the reproducibility of both single-voxel and multivoxel methods at 1.5 and 3-4 T. We have selected three clinical neurologic applications in which there has been a consensus as to the diagnostic value of MRS and summarize the information relevant to clinical applications. Finally, we speculate about some of the potential technical developments, either in progress or in the future, that may lead to improvements in the performance of proton MRS.

3T MR of the prostate: reducing susceptibility gradients by inflating the endorectal coil with a barium sulfate suspension.

Most prostate MRI/MRS examinations are performed with an endorectal coil inflated with air, leading to an air-tissue interface that induces magnetic susceptibility gradients within the gland. Inflation of the coil with a barium sulfate suspension is described and compared to inflation with air or liquid perfluorocarbon (PFC). The B(0) field in the prostate gland was mapped for five healthy volunteers when the endorectal coil was inflated with each of the three agents. A marked decrease in the posterior-anterior (P-A) field gradient and a significant improvement in field homogeneity were evident in the presence of a barium suspension and PFC relative to air. MRS data acquired from the prostate gland in the presence of air, PFC, and a barium suspension in the endorectal coil showed similar trends, demonstrating improvement in line-widths and spectral resolution when the barium suspension or the PFC were inflating the endorectal coil. On this basis we conclude that a barium suspension provides an available, cheap, and safe alternative to PFC, and we suggest that inflating the endorectal coil with a barium suspension should be considered for prostate MR studies, especially at high field strengths (such as 3T).

Sodium MRI of the human kidney at 3 Tesla.

The sodium concentration gradient in the kidney (from the cortex to the medulla) serves to regulate fluid homeostasis and is tightly coupled to renal function. It was previously shown that renal function and pathophysiology can be characterized in rat kidneys by measuring the sodium gradient with (23)Na MRI. This study demonstrates for the first time the ability of (23)Na MRI to map the distribution of sodium in the human kidney and to quantify the corticomedullary sodium gradient. The study was performed on a 3T Signa LX scanner (GE) using an in-house-built quadrature surface coil. (23)Na images of volunteers were acquired using a 3D coronal gradient-echo sequence at a spatial resolution of 0.3 x 0.3 x 1.5 cm(3) in a 25-min scan time. The signal intensity (relative to the noise) increased linearly from the cortex to each of the medullae with a mean slope of 1.6 +/- 0.2 in relative arbitrary units per mm (Rel.u./mm, N = 6) and then decreased, as expected, toward the renal pelvis. Water deprivation (12 hr) induced a significant increase of 25% (P < 0.05) in this gradient. Based on these results, we suggest that sodium MRI can serve as a valuable noninvasive method for functional imaging of the human kidney.

Vascular perfusion of human lung cancer in a rat orthotopic model using dynamic contrast-enhanced magnetic resonance imaging.

Lung cancer is the leading cause of death among cancers. Early detection and diagnosis present a major goal in the efforts to improve survival rates of lung cancer patients. Changes in angiogenic activity and microvascular perfusion properties in cancers can serve as markers of malignancy. The aim of this study was to employ MRI means to measure the microvascular perfusion parameters of orthotopic nonsmall cell lung cancer, using the experimental rat model. Anatomical and dynamic contrast-enhanced lung images were acquired at high spatial resolution, and registered and analyzed, pixel by pixel and globally, by means of a model-based algorithm. The MRI output yielded color-coded parametric images of the influx and efflux transcapillary transfer constants that indicated rapid microvascular perfusion. The transfer constants were about 1 order of magnitude higher than those found in other tumors or in nonorthotopic lung cancer, with the influx constant median value of 0.42 min(-1) and the efflux constant median value of 1.61 min(-1). The rapid perfusion was in accord with the immunostaining of the capillaries, which suggested the tumor exploitation of the existing alveolar vessels. The results showed that high resolution, dynamic, contrast-enhanced MRI is an effective tool for the quantitative measurement of spatial and temporal changes in lung cancer perfusion and vasculature.