An Economist Best History Book 2017
"History as it should be written."-Barry Cunliffe,
Guardian "Scott hits the nail squarely on
the head by exposing the staggering price our ancestors paid for
...civilization and political order."-Walter Scheidel, Financial
Times Why did humans abandon hunting and gathering
for sedentary communities dependent on livestock and cereal grains,
and governed by precursors of today's states? Most people believe
that plant and animal domestication allowed humans, finally, to
settle down and form agricultural villages, towns, and states,
which made possible civilization, law, public order, and a
presumably secure way of living. But archaeological and historical
evidence challenges this narrative. The first agrarian states, says
James C. Scott, were born of accumulations of domestications: first
fire, then plants, livestock, subjects of the state, captives, and
finally women in the patriarchal family-all of which can be viewed
as a way of gaining control over reproduction. Scott explores why
we avoided sedentism and plow agriculture, the advantages of mobile
subsistence, the unforeseeable disease epidemics arising from
crowding plants, animals, and grain, and why all early states are
based on millets and cereal grains and unfree labor. He also
discusses the "barbarians" who long evaded state control, as a way
of understanding continuing tension between states and nonsubject
peoples.
For two thousand years the disparate groups that now reside in Zomia (a mountainous region the size of Europe that consists of portions of seven Asian countries) have fled the projects of the ...organized state societies that surround them-slavery, conscription, taxes, corvée labor, epidemics, and warfare. This book, essentially an "anarchist history," is the first-ever examination of the huge literature on state-making whose author evaluates why people would deliberately and reactively remain stateless. Among the strategies employed by the people of Zomia to remain stateless are physical dispersion in rugged terrain; agricultural practices that enhance mobility; pliable ethnic identities; devotion to prophetic, millenarian leaders; and maintenance of a largely oral culture that allows them to reinvent their histories and genealogies as they move between and around states.
In accessible language, James Scott, recognized worldwide as an eminent authority in Southeast Asian, peasant, and agrarian studies, tells the story of the peoples of Zomia and their unlikely odyssey in search of self-determination. He redefines our views on Asian politics, history, demographics, and even our fundamental ideas about what constitutes civilization, and challenges us with a radically different approach to history that presents events from the perspective of stateless peoples and redefines state-making as a form of "internal colonialism." This new perspective requires a radical reevaluation of the civilizational narratives of the lowland states. Scott's work on Zomia represents a new way to think of area studies that will be applicable to other runaway, fugitive, and marooned communities, be they Gypsies, Cossacks, tribes fleeing slave raiders, Marsh Arabs, or San-Bushmen.
The effectiveness of the annual influenza vaccine has declined in recent years, especially for the H3N2 component, and is a concern for global public health. A major cause for this lack in ...effectiveness has been attributed to the egg-based vaccine production process. Substitutions on the hemagglutinin glycoprotein (HA) often arise during virus passaging that change its antigenicity and hence vaccine effectiveness. Here, we characterize the effect of a prevalent substitution, L194P, in egg-passaged H3N2 viruses. X-ray structural analysis reveals that this substitution surprisingly increases the mobility of the 190-helix and neighboring regions in antigenic site B, which forms one side of the receptor binding site (RBS) and is immunodominant in recent human H3N2 viruses. Importantly, the L194P substitution decreases binding and neutralization by an RBS-targeted broadly neutralizing antibody by three orders of magnitude and significantly changes the HA antigenicity as measured by binding of human serum antibodies. The receptor binding mode and specificity are also altered to adapt to avian receptors during egg passaging. Overall, these findings help explain the low effectiveness of the seasonal vaccine against H3N2 viruses, and suggest that alternative approaches should be accelerated for producing influenza vaccines as well as isolating clinical isolates.
To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF).
The Update Committee completed a review and analysis of pertinent data ...published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness.
The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.
Although the incorporation of research biopsies into clinical trials is increasing, limited information is available about how study protocols and informed consents integrate and describe their use.
...All therapeutic clinical trials in which image-guided research biopsies were performed from January 1, 2005, to October 1, 2010, were identified from an interventional radiology database. Data from study protocols and informed consents were extracted and analyzed. Procedural complications were recorded.
A total of 57 clinical trials were identified, of which 38 (67%) contained at least one mandatory biopsy. The analysis of the research biopsy tumor tissue was a study end point in 95% of trials. The primary indication for a research biopsy was for integral biomarker analysis in 32% and for correlative science in 68% of trials. A statistical analytic plan for the correlative science research biopsy tumor tissue was mentioned in 26%, described as exploratory in 51%, and not mentioned in 23% of trials. For studies with mandatory biopsies, biopsy was an eligibility criterion in 71% of trials, and a statistical justification for the research biopsy sample size was present in 50% of trials. A total of 745 research biopsies were performed on 576 patients. Overall and major complication rates were 5.2% (39 of 745 biopsies) and 0.8% (six of 745 biopsies), respectively. Complication rates for intrathoracic and abdominal/pelvic solid organ biopsies were 17.1% (36 of 211 biopsies) and 1.6% (three of 189 biopsies), respectively. Site-stratified research biopsy-related risks were discussed in five consents.
A better representation of the risks and benefits of research biopsies in study protocols and informed consents is needed.
Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in ...advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501). We report results of the second prespecified interim analysis (150 events).
Patients with ALK inhibitor-naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected.
Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio HR, 0.49 95% CI, 0.35 to 0.68; log-rank
< .0001; median, 24.0
11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4
9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 95% CI, 0.49 to 1.00; log-rank
= .049). Brigatinib daily area under the plasma concentration-time curve was not a predictor of PFS (HR, 1.005 95% CI, 0.98 to 1.031;
= .69).
Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.
Tissue engineering is a rapidly advancing field in regenerative medicine, with much research directed towards the production of new biomaterial scaffolds with tailored properties to generate ...functional tissue for specific applications. Recently, principles of sustainability, eco-efficiency and green chemistry have begun to guide the development of a new generation of materials, such as cellulose, as an alternative to conventional polymers based on conversion of fossil carbon (e.g., oil) and finding technologies to reduce the use of animal and human derived biomolecules (e.g., foetal bovine serum). Much of this focus on cellulose is due to it possessing the necessary properties for tissue engineering scaffolds, including biocompatibility, and the relative ease with which its characteristics can be tuned through chemical modification to adjust mechanical properties and to introduce various surface modifications. In addition, the sustainability of producing and manufacturing materials from cellulose, as well as its modest cost, makes cellulose an economically viable feedstock. This review focusses specifically on the use of modified cellulose materials for tissue culturing applications. We will investigate recent techniques used to promote scaffold function through physical, biochemical and chemical scaffold modifications, and describe how these have been utilised to reduce reliance on the addition of matrix ligands such as foetal bovine serum.
Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells ...were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.
FTO, an mRNA N6-methyladenosine (m6A) demethylase, was reported to promote leukemogenesis. Using structure-based rational design, we have developed two promising FTO inhibitors, namely FB23 and ...FB23-2, which directly bind to FTO and selectively inhibit FTO's m6A demethylase activity. Mimicking FTO depletion, FB23-2 dramatically suppresses proliferation and promotes the differentiation/apoptosis of human acute myeloid leukemia (AML) cell line cells and primary blast AML cells in vitro. Moreover, FB23-2 significantly inhibits the progression of human AML cell lines and primary cells in xeno-transplanted mice. Collectively, our data suggest that FTO is a druggable target and that targeting FTO by small-molecule inhibitors holds potential to treat AML.
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•Structure-guided design and optimization yield potent FTO inhibitors•mRNA m6A acts as the major effector of the inhibitor/FTO axis in AML cells•FTO inhibitor FB23-2 displays therapeutic effects in PDX AML models•Targeting epitranscriptomic RNA methylation holds potential to treat AML
Huang et al. use structure-based rational design to develop FB23-2, an inhibitor of the mRNA m6A demethylase FTO. FB23-2 suppresses proliferation and promotes the differentiation of acute myeloid leukemia (AML) cells and prolongs survival of patient-derived AML mouse models.
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