Late Eocene-Oligocene granulite facies garnet-sillimanite migmatites from the Mogok Metamorphic belt, Myanmar, and implications for timing of slip along the Sagaing Fault

MPS is grateful to the Oxford-Burma Aung San Suu Kyi trust for funding research and field visits to Mogok. U-Th-Pb geochronology was funded by UCSB and NSF grants EAR-1348003 and EAR-1551054 to BH.The Mogok Metamorphic Belt (MMB) in Myanmar is a polymetamorphic, mainly Paleogene granulite-uppermost amphibolite facies terrane consisting mainly of marbles and calc-silicates hosting spinel, ruby and sapphire. Jurassic charnockite-syenite intrusions, as well as Eocene-Miocene leucogranite intrusions are also present. Pelitic rocks are uncommon, and where present, have sillimanite, both as primary inclusions in garnet and as secondary Bt + Sil coronas around garnet. Core samples from the Kyi-Tauk-Pauk gold mine at Thabeikkiyin, north of Mandalay, are mostly Grt + Bt + Sill gneisses and migmatites with uncommon interbanded Opx + Grt + Bt gneisses. Pseudosection modelling suggests prograde garnet growth occurred by biotite-dehydration melting that reached peak P–T conditions of 870–970 °C and ~ 0.9 GPa, and was followed by garnet breakdown forming coarse retrograde Bt + Sil coronas. U[sbnd]Pb monazite data show an early high-grade granulite event at 43–32 Ma, and a later upper amphibolite sillimanite-grade event peaking at 23–20 Ma, with a change in monazite chemistry after c. 22 Ma that is consistent with fluid/(melt) interaction and garnet breakdown. Elevated Th/U ratios from ~35 to 22 Ma, and at ~18 Ma are compatible with melt influx at that time, timing that is similar to the age of the regional Kabaing leucogranite in the Mogok valley area. Our data show that peak granulite facies metamorphism along the Mogok Metamorphic belt was mainly Middle Eocene-Early Oligocene, with upper amphibolite facies metamorphism extending to earliest Miocene. The MMB is cut abruptly by the Sagaing fault, a large-scale dextral fault that extends from the Andaman Sea north to the East Himalayan syntaxis. Our new U[sbnd]Pb monazite data constrain the oldest age of initiation of the eastern branch of the cross-cutting Sagaing dextral strike-slip fault atPostprintPeer reviewe

Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar : a retrospective cohort study

INTRODUCTION: Despite HIV viral load (VL) monitoring being serial, most studies use a cross-sectional design to evaluate the virological status of a cohort. The objective of our study was to use a simplified approach to calculate viraemic-time: the proportion of follow-up time with unsuppressed VL above the limit of detection. We estimated risk factors for higher viraemic-time and whether viraemic-time predicted mortality in a second-line antiretroviral treatment (ART) cohort in Myanmar. METHODS: We conducted a retrospective cohort analysis of people living with HIV (PLHIV) who received second-line ART for a period >6 months and who had at least two HIV VL test results between 01 January 2014 and 30 April 2018. Fractional logistic regression assessed risk factors for having higher viraemic-time and Cox proportional hazards regression assessed the association between viraemic-time and mortality. Kaplan-Meier curves were plotted to illustrate survival probability for different viraemic-time categories. RESULTS: Among 1,352 participants, 815 (60.3%) never experienced viraemia, and 172 (12.7%), 214 (15.8%), and 80 (5.9%) participants were viraemic <20%, 20–49%, and 50–79% of their total follow-up time, respectively. Few (71; 5.3%) participants were ≥80% of their total follow-up time viraemic. The odds for having higher viraemic-time were higher among people with a history of injecting drug use (aOR 2.01, 95% CI 1.30–3.10, p = 0.002), sex workers (aOR 2.10, 95% CI 1.11–4.00, p = 0.02) and patients treated with lopinavir/ritonavir (vs. atazanavir; aOR 1.53, 95% CI 1.12–2.10, p = 0.008). Viraemic-time was strongly associated with mortality hazard among those with 50–79% and ≥80% viraemic-time (aHR 2.92, 95% CI 1.21–7.10, p = 0.02 and aHR 2.71, 95% CI 1.22–6.01, p = 0.01). This association was not observed in those with viraemic-time <50%. CONCLUSIONS: Key populations were at risk for having a higher viraemic-time on second-line ART. Viraemic-time predicts clinical outcomes. Differentiated services should target subgroups at risk for a higher viraemic-time to control both HIV transmission and mortality

Suleiman-El-Hattab syndrome: A histone modification disorder caused by TASP1 deficiency.

BACKGROUND: TASP1 encodes an endopeptidase activating histone methyltransferases of the KMT2 family. Homozygous loss-of-function variants in TASP1 have recently been associated with Suleiman-El-Hattab syndrome. We report six individuals with Suleiman-El-Hattab syndrome and provide functional characterization of this novel histone modification disorder in a multi-omics approach. Methods Chromosomal microarray/exome sequencing in all individuals. Western blotting from fibroblasts in two individuals. RNA sequencing and proteomics from fibroblasts in one individual. Methylome analysis from blood in two individuals. Knock-out of tasp1 orthologue in zebrafish and phenotyping. RESULTS: All individuals had biallelic TASP1 loss-of-function variants and a phenotype including developmental delay, multiple congenital anomalies (including cardiovascular and posterior fossa malformations), a distinct facial appearance, and happy demeanor. Western blot revealed absence of TASP1. RNA sequencing/proteomics showed HOX gene downregulation (HOXA4, HOXA7, HOXA1, HOXB2) and dysregulation of transcription factor TFIIA. A distinct methylation profile intermediate between control and Kabuki syndrome (KMT2D) profiles could be produced. Zebrafish tasp1 knock-out revealed smaller head size and abnormal cranial cartilage formation in tasp1 crispants. CONCLUSION: This work further delineates Suleiman-El-Hattab syndrome, a recognizable neurodevelopmental syndrome. Possible downstream mechanisms of TASP1 deficiency include perturbed HOX gene expression and dysregulated TFIIA complex. Methylation pattern suggests that Suleiman-El-Hattab syndrome can be categorized into the group of histone modification disorders including Wiedemann-Steiner and Kabuki syndrome