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Myanmar in Crisis brings together scholars from across the social sciences to analyse the dual crises of COVID-19 and the 2021 military coup. All of the essays address one of four themes around the concept of crisis: society in crisis, a state in crisis, an economy in crisis, and international relations in crisis. Several authors examine the contested nature of state authority in the post-coup revolutionary context, including the emergence of new governance dynamics; others discuss heterogenous forms of resistance and the potential for building a more inclusive, just, and tolerant society in the future of Myanmar. The volume also explores the economic crisis caused by the pandemic and the coup and its devastating effects on people's lives and livelihoods: the authors provide a deep dive into the impacts of restrictive COVID-19 prevention measures on local communities, the growing livelihoods crisis since the coup, and the impacts of both crises on foreign trade and investment. Scaling up from that local perspective, the book also looks at Myanmar's history of foreign relations, the response of the international community to the coup and the challenges faced by foreign governments and regional bodies in navigating the deteriorating political situation. Held together, the volume highlights the ongoing state of crisis in Myanmar, its impact on society and the possibilities for recovery and reform, amidst a powerful new revolutionary movement. Beyond providing crucial insights to Southeast Asian area specialists, the book offers deep insights into the way that multiple crises interact, amplify one another, and open up possibilities for hope amidst tragedy.

In Myanmar, the idea of ‘indigeneity’ has been mobilised in two radically different ways. Ethnonationalist groups such as the Chin National Front and the Karen National Union have utilised the concept to lobby for increased autonomy in international forums such as the United Nations, while the Burmese state has used the idea of indigeneity (or native-ness, typically translated as taingyinthar in Burmese) to exclude certain minorities — most prominently the Rohingya — by explicitly striking them from the official list of Myanmar's ‘national races’. To clarify how this definitional tension has developed, this article will situate the competing Burmese appeals to indigeneity within the history of international indigeneity politics, and compare the Burmese ‘Indigenous situation’ to other Asian countries that have addressed the question of who counts and does not count as Indigenous.

Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53 , CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification. Comprehensive integration of mutational and structural alterations in clinically-annotated DLBCL patient samples provides a novel molecular classification of the disease.

Background Scaling up evidence-based interventions to improve physical activity (PA) is important for enhancing health outcomes. The Healthy4U (H4U) program, initially successful in improving PA and health outcomes among ambulatory hospital patients, was expanded from one regional hospital to five rural hospitals. This study retrospectively examines the feasibility of implementing H4U at Scale (H4U-AS) over 12 months. Methods A feasibility implementation evaluation was conducted retrospectively using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. The following variables were assessed within each RE-AIM domain: Reach: Number of program participants. Effectiveness: Measured changes in PA (Metabolic Equivalent of Task minutes (MET-mins/week)), sedentary behaviour (hours/day spent seated), fruit and vegetable intake (serves/day), and nicotine dependence score (Fagerström Test for Nicotine Dependence (FTND)) using paired t-tests or Wilcoxon signed-rank tests. Adoption: Type of setting, program integration, and behaviour change training uptake. Implementation: Participant and hospital recruitment adherence. Maintenance: Continuation of the program. Results Reach: In total, 37 participants were recruited during the 6-month recruitment period; pre- and post-data were available for 33. Effectiveness: PA increased from a median of 460 MET-mins/week to 840 ( p  < 0.001). Sedentary behaviour decreased from 8.0 h/day to 7.0 ( p  < 0.001). Vegetable intake increased from 3.0 serves/day to 3.5 ( p  = 0.001). Fruit intake did not change significantly ( p  = 0.228). Nicotine dependence decreased non-significantly from 5.0 to 4.5 ( p  = 0.08). Adoption: The program was successfully implemented in five rural hospitals; feedback from hospital representatives indicated that recruitment procedures were integrated into existing hospital workflows. To support recruitment, processes were adapted to include mailing out invites to people on elective surgery wait lists. Implementation: 86% of participants completed the minimum 4 of 6 available sessions, and all hospitals recruited during the program period. Maintenance: Funding for the project was not available beyond the 12-month period. As a result, recruitment into the program was ceased. Conclusion H4U-AS suggests that implementing an evidence-based PA intervention from one regional hospital to five rural hospitals may be feasible. Participants improved PA and dietary behaviours. However, limited participant recruitment during the short recruitment period, and funding cessation, impacted the extent to which the program could be offered and evaluated at scale.

Glucocorticoids (GC) elicit skeletal muscle capillary rarefaction, which can subsequently impair blood distribution and muscle function; however, the mechanisms have not been established. We hypothesized that CORT would inhibit endothelial cell survival signals but that treatment with the alpha-1 adrenergic receptor inhibitor prazosin, which leads to angiogenesis in skeletal muscle of healthy rats, would reverse these effects and induce angiogenesis within the skeletal muscle of corticosterone (CORT)-treated rats. Male Sprague Dawley rats were implanted subcutaneously with CORT pellets (400 mg/rat), with or without concurrent prazosin treatment (50mg/L in drinking water), for 1 or 2 weeks. Skeletal muscle capillary rarefaction, as indicated by a significant reduction in capillary-to-fiber ratio (C:F), occurred after 2 weeks of CORT treatment. Concurrent prazosin administration prevented this capillary rarefaction in CORT-treated animals but did not induce angiogenesis or arteriogenesis as was observed with prazosin treatment in control rats. CORT treatment reduced the mRNA level of Angiopoietin-1 (Ang-1), which was partially offset in the muscles of rats that received 2 weeks of co-treatment with prazosin. In 2W CORT animals, prazosin treatment elicited a significant increase in vascular endothelial growth factor-A (VEGF-A) mRNA and protein. Conversely prazosin did not rescue CORT-induced reductions in transforming growth factor beta-1 (TGFβ1 and matrix metalloproteinase-2 (MMP-2) mRNA. To determine if CORT impaired shear stress dependent signaling, cultured rat skeletal muscle endothelial cells were pre-treated with CORT (600nM) for 48 hours, then exposed to 15 dynes/cm2 shear stress or maintained with no flow. CORT blunted the shear stress-induced increase in pSer473 Akt, while pThr308 Akt, ERK1/2 and p38 phosphorylation and nitric oxide (NO) production were unaffected. This study demonstrates that GC-mediated capillary rarefaction is associated with a reduction in Ang-1 mRNA within the skeletal muscle microenvironment and that concurrent prazosin treatment effectively increases VEGF-A levels and prevents capillary loss.

Osteoporosis and low bone mass are currently estimated to be a major public health risk affecting > 50% of the female population over the age of 50. Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. FPPS, a key branchpoint of the mevalonate pathway, catalyzes the successive condensation of isopentenyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. To understand the molecular events involved in inhibition of FPPS by N-BPs, we used protein crystallography, enzyme kinetics, and isothermal titration calorimetry. We report here high-resolution x-ray structures of the human enzyme in complexes with risedronate and zoledronate, two of the leading N-BPs in clinical use. These agents bind to the dimethylallyl/ geranyl pyrophosphate ligand pocket and induce a conformational change. The interactions of the N-BP cyclic nitrogen with Thr-201 and Lys-200 suggest that these inhibitors achieve potency by positioning their nitrogen in the proposed carbocation-binding site. Kinetic analyses reveal that inhibition is competitive with geranyl pyrophosphate and is of a slow, tight binding character, indicating that isomerization of an initial enzyme-inhibitor complex occurs with inhibitor binding. Isothermal titration calorimetry indicates that binding of N-BPs to the apoenzyme is entropydriven, presumably through desolvation entropy effects. These experiments reveal the molecular binding characteristics of an important pharmacological target and provide a route for further optimization of these important drugs.

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient’s skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies. A cancer genome The technologies that made it possible to characterize individual African and Chinese genomes have broad application in the biomedical field. A demonstration of what can be achieved in a medical context is the first comprehensive sequence of an individual cancer genome, for a patient with acute myeloid leukaemia. By comparing DNA from cancer and normal tissue from the same individual, ten mutations of possible relevance for pathogenesis were identified. As well as pointing to genes that may respond to targeted therapy, this work is a step towards the long-term goal of establishing the contextual relevance of such mutants, a process that will involve the analysis of many more personal genomes.

Quantum Chromodynamics, the theory of quarks and gluons, whose interactions can be described by a local SU(3) gauge symmetry with charges called “color quantum numbers”, is reviewed; the goal of this review is to provide advanced Ph.D. students a comprehensive handbook, helpful for their research. When QCD was “discovered” 50 years ago, the idea that quarks could exist, but not be observed, left most physicists unconvinced. Then, with the discovery of charmonium in 1974 and the explanation of its excited states using the Cornell potential, consisting of the sum of a Coulomb-like attraction and a long range linear confining potential, the theory was suddenly widely accepted. This paradigm shift is now referred to as the November revolution . It had been anticipated by the observation of scaling in deep inelastic scattering, and was followed by the discovery of gluons in three-jet events. The parameters of QCD include the running coupling constant, α s ( Q 2 ) , that varies with the energy scale Q 2 characterising the interaction, and six quark masses. QCD cannot be solved analytically, at least not yet, and the large value of α s at low momentum transfers limits perturbative calculations to the high-energy region where Q 2 ≫ Λ QCD 2 ≃ (250 MeV) 2 . Lattice QCD (LQCD), numerical calculations on a discretized space-time lattice, is discussed in detail, the dynamics of the QCD vacuum is visualized, and the expected spectra of mesons and baryons are displayed. Progress in lattice calculations of the structure of nucleons and of quantities related to the phase diagram of dense and hot (or cold) hadronic matter are reviewed. Methods and examples of how to calculate hadronic corrections to weak matrix elements on a lattice are outlined. The wide variety of analytical approximations currently in use, and the accuracy of these approximations, are reviewed. These methods range from the Bethe–Salpeter, Dyson–Schwinger coupled relativistic equations, which are formulated in both Minkowski or Euclidean spaces, to expansions of multi-quark states in a set of basis functions using light-front coordinates, to the AdS/QCD method that imbeds 4-dimensional QCD in a 5-dimensional deSitter space, allowing confinement and spontaneous chiral symmetry breaking to be described in a novel way. Models that assume the number of colors is very large, i.e. make use of the large N c -limit, give unique insights. Many other techniques that are tailored to specific problems, such as perturbative expansions for high energy scattering or approximate calculations using the operator product expansion are discussed. The very powerful effective field theory techniques that are successful for low energy nuclear systems (chiral effective theory), or for non-relativistic systems involving heavy quarks, or the treatment of gluon exchanges between energetic, collinear partons encountered in jets, are discussed. The spectroscopy of mesons and baryons has played an important historical role in the development of QCD. The famous X,Y,Z states – and the discovery of pentaquarks – have revolutionized hadron spectroscopy; their status and interpretation are reviewed as well as recent progress in the identification of glueballs and hybrids in light-meson spectroscopy. These exotic states add to the spectrum of expected q q ¯ mesons and qqq baryons. The progress in understanding excitations of light and heavy baryons is discussed. The nucleon as the lightest baryon is discussed extensively, its form factors, its partonic structure and the status of the attempt to determine a three-dimensional picture of the parton distribution. An experimental program to study the phase diagram of QCD at high temperature and density started with fixed target experiments in various laboratories in the second half of the 1980s, and then, in this century, with colliders. QCD thermodynamics at high temperature became accessible to LQCD, and numerical results on chiral and deconfinement transitions and properties of the deconfined and chirally restored form of strongly interacting matter, called the Quark–Gluon Plasma (QGP), have become very precise by now. These results can now be confronted with experimental data that are sensitive to the nature of the phase transition. There is clear evidence that the QGP phase is created. This phase of QCD matter can already be characterized by some properties that indicate, within a temperature range of a few times the pseudocritical temperature, the medium behaves like a near ideal liquid. Experimental observables are presented that demonstrate deconfinement. High and ultrahigh density QCD matter at moderate and low temperatures shows interesting features and new phases that are of astrophysical relevance. They are reviewed here and some of the astrophysical implications are discussed. Perturbative QCD and methods to describe the different aspects of scattering processes are discussed. The primary parton–parton scattering in a collision is calculated in perturbative QCD with increasing complexity. The radiation of soft gluons can spoil the perturbative convergence, this can be cured by resummation techniques, which are also described here. Realistic descriptions of QCD scattering events need to model the cascade of quark and gluon splittings until hadron formation sets in, which is done by parton showers. The full event simulation can be performed with Monte Carlo event generators, which simulate the full chain from the hard interaction to the hadronic final states, including the modelling of non-perturbative components. The contribution of the LEP experiments (and of earlier collider experiments) to the study of jets is reviewed. Correlations between jets and the shape of jets had allowed the collaborations to determine the “color factors” – invariants of the SU(3) color group governing the strength of quark–gluon and gluon–gluon interactions. The calculated jet production rates (using perturbative QCD) are shown to agree precisely with data, for jet energies spanning more than five orders of magnitude. The production of jets recoiling against a vector boson, W ± or Z , is shown to be well understood. The discovery of the Higgs boson was certainly an important milestone in the development of high-energy physics. The couplings of the Higgs boson to massive vector bosons and fermions that have been measured so far support its interpretation as mass-generating boson as predicted by the Standard Model. The study of the Higgs boson recoiling against hadronic jets (without or with heavy flavors) or against vector bosons is also highlighted. Apart from the description of hard interactions taking place at high energies, the understanding of “soft QCD” is also very important. In this respect, Pomeron – and Odderon – exchange, soft and hard diffraction are discussed. Weak decays of quarks and leptons, the quark mixing matrix and the anomalous magnetic moment of the muon are processes which are governed by weak interactions. However, corrections by strong interactions are important, and these are reviewed. As the measured values are incompatible with (most of) the predictions, the question arises: are these discrepancies first hints for New Physics beyond the Standard Model? This volume concludes with a description of future facilities or important upgrades of existing facilities which improve their luminosity by orders of magnitude. The best is yet to come!