The Origins of Bagan: The archaeological landscape of Upper Burma to AD 1300.

The archaeological landscape of Upper Burma from the middle of the first millennium BC to the Bagan period in the 13th-14th century AD is a landscape of continuity. Finds of polished stone and bronze artifacts suggest the existence of early metal-using cultures in the Chindwin and Samon River Valleys, and along parts of the Ayeyarwady plain. Increasing technological and settlement complexity in the Samon Valley suggests that a distinctive culture whose agricultural and trade success can be read in the archaeological record of the Late Prehistoric period developed there. The appearance of the early urban "Pyu" system of walled central places during the early first millennium AD seems to have involved a spread of agricultural and management skills and population from the Samon. The leaders of the urban centres adopted Indic symbols and Sanskrit modes of kingship to enhance and extend their authority. The early urban system was subject over time to a range of stresses including siltation of water systems, external disruption and social changes as Buddhist notions of leadership eclipsed Brahmanical ones. The archaeological evidence indicates that a settlement was forming at Bagan during the last centuries of the first millennium AD. By the mid 11th century Bagan began to dominate Upper Burma, and the region began a transition from a system of largely autonomous city states to a centralised kingdom. Inscriptions of the 11th to 13th centuries indicate that as the Bagan Empire expanded it subsumed the agricultural lands that had been developed by the Pyu

Elevated globotriaosylsphingosine is a hallmark of Fabry disease

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Screening for distant metastases in patients with ipsilateral breast tumor recurrence: the impact of different imaging modalities on distant recurrence-free interval

Purpose In patients with ipsilateral breast tumor recurrence (IBTR), the detection of distant disease determines whether the intention of the treatment is curative or palliative. Therefore, adequate preoperative staging is imperative for optimal treatment planning. The aim of this study is to evaluate the impact of conventional imaging techniques, including chest X-ray and/or CT thorax-(abdomen), liver ultrasonography(US), and skeletal scintigraphy, on the distant recurrence-free interval (DRFI) in patients with IBTR, and to compare conventional imaging with 18F-FDG PET-CT or no imaging at all. Methods This study was exclusively based on the information available at time of diagnoses of IBTR. To adjust for differences in baseline characteristics between the three imaging groups, a propensity score (PS) weighted method was used. Results Of the 495 patients included in the study, 229 (46.3%) were staged with conventional imaging, 89 patients (19.8%) were staged with 18F-FDG PET-CT, and in 168 of the patients (33.9%) no imaging was used (N=168). After a follow-up of approximately 5 years, 14.5% of all patients developed a distant recurrence as frst event after IBTR. After adjusting for the PS weights, the Cox regression analyses showed that the diferent staging methods had no signifcant impact on the DRFI. Conclusions This study showed a wide variation in the use of imaging modalities for staging IBTR patients in the Netherlands. After using PS weighting, no statistically signifcant impact of the diferent imaging modalities on DRFI was shown. Based on these results, it is not possible to recommend staging for distant metastases using 18F-FDG PET-CT over conventional imaging technique

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

Unexplained left ventricular hypertrophy: consider a diagnosis of Fabry's disease

Lysosomal storage disorders are a group of disorders characterised by the deficiency of a specific lysosomal hydrolase. These diseases are rare, with only a few hundred patients in the Netherlands. Fabry's disease, an X-linked lysosomal storage disorder, is caused by a deficiency of the lysosomal enzyme α-galactosidase A which results in, among other things, left ventricular hypertrophy, renal failure and cerebrovascular events. Patients with Fabry's disease, especially males, have a decreased life expectancy. Recent studies have shown that Fabry's disease may be much more common among patients with left ventricular hypertrophy (LVH) than previously thought. Up to 7% of male patients with left ventricular hypertrophy and up to 12% of female patients with unexplained LVH were found to suffer from Fabry's disease. Thus, Fabry's disease should be considered in patients with unexplained LVH. This case report summarises the main features of the disease. In addition recent developments concerning prevalence, diagnosis and the current available treatments are discussed and an algorithm on who and how to screen for Fabry's disease is presented