The United States and Israel: the risk of growing apart; if illiberal democracy prevails in Israel, the special relationship may not survive

United States Secretary of State Mike Pompeo’s assertion that “the establishment of Israeli civilian settlements in the West Bank is not per se inconsistent with inter­national law” is merely the latest example of how US and Israeli policies have marched almost in lockstep since Donald Trump’s inauguration as president. However, the United States and Israel have shared an intense and intimate relationship that long predates the Trump Administration and goes beyond the chemistry of individual leaders. In many respects, in fact, that relationship is unique in American foreign rela­tions and uniquely critical to Israeli security. It is grounded in a shared narra­tive of biblically inspired frontier societies that have gathered in immigrants and refu­gees, tamed the wilderness, and built liberal democracy. This explains the broadly recep­tive environment in the United States for the message of US-Israeli commonality. Never­theless, the durability of the relationship is not guaranteed. If the societies and politi­cal cultures of the two countries either continue to develop along parallel, illiberal lines or shift simultaneously in a more liberal direction, the connection be­tween them will be preserved, or even strengthened. However, if they diverge, and especially if Israel maintains its rightward drift while America moves in an opposite direction, the normative foundation of the relationship will erode, with ominous implications for Israel. (author's abstract

Chaos and Quantum Thermalization

We show that a bounded, isolated quantum system of many particles in a specific initial state will approach thermal equilibrium if the energy eigenfunctions which are superposed to form that state obey {\it Berry's conjecture}. Berry's conjecture is expected to hold only if the corresponding classical system is chaotic, and essentially states that the energy eigenfunctions behave as if they were gaussian random variables. We review the existing evidence, and show that previously neglected effects substantially strengthen the case for Berry's conjecture. We study a rarefied hard-sphere gas as an explicit example of a many-body system which is known to be classically chaotic, and show that an energy eigenstate which obeys Berry's conjecture predicts a Maxwell--Boltzmann, Bose--Einstein, or Fermi--Dirac distribution for the momentum of each constituent particle, depending on whether the wave functions are taken to be nonsymmetric, completely symmetric, or completely antisymmetric functions of the positions of the particles. We call this phenomenon {\it eigenstate thermalization}. We show that a generic initial state will approach thermal equilibrium at least as fast as $O(\hbar/\Delta)t^{-1}$, where $\Delta$ is the uncertainty in the total energy of the gas. This result holds for an individual initial state; in contrast to the classical theory, no averaging over an ensemble of initial states is needed. We argue that these results constitute a new foundation for quantum statistical mechanics.Comment: 28 pages in Plain TeX plus 2 uuencoded PS figures (included); minor corrections only, this version will be published in Phys. Rev. E; UCSB-TH-94-1

‘In shape and mind transformed’? Televised teaching and learning Shakespeare

Reality television offers the BBC the opportunity to fulfil its dual imperatives of education and entertainment, frequently constructed as anathematic. This article considers three recent examples of televised teaching and learning Shakespeare: When Romeo Met Juliet, Macbeth, the movie star and me, and Off By Heart: Shakespeare. It demonstrates the programmes’ fit with the reality genre through their common ingredients of authenticity, contained locations, hybridity, experts, fallible and flawed participants, articulation and reconciliation of social difference. Moreover, all three share an emphasis on a reality television staple: transformation, in terms of the participants’ knowledge, skills and personal growth, but also in relation to television audiences and the British education system. The programmes might thus usefully be understood as part of a reality television subgenre, evolving in Britain since the late 1970s, of Shmake-over. This article is published as part of a collection to commemorate the 400th anniversary of William Shakespeare’s death

Reducing the impact of physical inactivity: evidence to support the case for targeting people with chronic mental and physical conditions

Background : Recent evidence suggests that small increases in the physical activity of those considered least active can have a bigger health impact than raising levels of those already achieving or close to achieving recommendations. Profiling the characteristics of those who are least active allows for appropriate targeting of interventions. This study therefore examined the characteristics of people in the lowest physical activity bracket. Methods : Data were taken from the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funded ‘South Yorkshire Cohort’, a longitudinal observational dataset of residents of South Yorkshire, England. Five separate outcomes based on a shortened version of the GPPAQ were used to represent the lowest levels of physical activity. Potential predictors examined were age, sex, body mass index, ethnicity, chronic conditions, current employment and deprivation. Descriptive statistics and logistic regression were conducted. Results : Individuals with chronic mental and physical conditions (fatigue, insomnia, anxiety, depression, diabetes, breathing problems, high blood pressure, heart disease, stroke and cancer) were more likely to report the lowest levels of physical activity across all five outcomes. Demographic variations were also observed. Conclusions : Targeting people with chronic mental and physical conditions has the potential to reduce the impact of physical inactivity.</p

Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication

Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies

Objective To compare the safety and efficacy of overnight closed loop delivery of insulin (artificial pancreas) with conventional insulin pump therapy in adults with type 1 diabetes

Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTS: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance

Effect of Hypoglycemia on Inflammatory Responses and the Response to Low Dose Endotoxemia in Humans

Context: Hypoglycemia is emerging as a risk for cardiovascular events in diabetes. We hypothesized that hypoglycemia activates the innate immune system, which is known to increase cardiovascular risk. Objective: To determine whether hypoglycemia modifies subsequent innate immune system responses. Design and Setting: Single-blinded, prospective study of three independent parallel groups. Participants and Interventions: Twenty-four healthy participants underwent either a hyperinsulinemic-hypoglycemic (2.5 mmol/l), euglycemic (6.0 mmol/l) or sham-saline clamp (n=8 for each group). Forty-eight hours later, all participants received low-dose (0.3 ng/kg) intravenous endotoxin. Main outcome measures: We studied in-vivo monocyte mobilization and monocyte-platelet interactions. Results: Hypoglycemia increased total leucocytes (9.98±1.14 x109/l vs euglycemia: 4.38±0.53 x109/l; P<0.001 vs sham-saline: 4.76±0.36 x109/l; P<0.001) (mean±SEM), mobilized proinflammatory intermediate monocytes (42.20±7.52/μl vs euglycemia: 20.66±3.43/μl; P<0.01 vs sham-saline: 26.20±3.86/μl; P<0.05) and non-classical monocytes (36.16±4.66/μl vs euglycemia: 12.72±2.42/μl; P<0.001 vs sham-saline: 19.05±3.81/μl; P<0.001). Following hypoglycemia vs euglycemia, platelet aggregation to agonist (AUC) increased (73.87±7.30 vs 52.50±4.04; P<0.05) and formation of monocyte-platelet aggregates increased (96.05±14.51/μl vs 49.32±6.41/μl; P<0.05). Within monocyte subsets, hypoglycemia increased aggregation of intermediate monocytes (10.51±1.42/μl vs euglycemia: 4.19±1.08/μl; P<0.05 vs sham-saline: 3.81±1.42/μl; P<0.05) and non-classical monocytes (9.53±1.08/μl vs euglycemia: 2.86±0.72/μl; P<0.01 vs sham-saline: 3.08±1.01/μl; P<0.05) with platelets compared to controls. Hypoglycemia led to greater leucocyte mobilization in response to subsequent low-dose endotoxin challenge (10.96±0.97 vs euglycemia: 8.21±0.85 x109/l; P<0.05). Conclusions: Hypoglycemia mobilizes monocytes, increases platelet reactivity, promotes interaction between platelets and proinflammatory monocytes, and potentiates the subsequent immune response to endotoxin. These changes may contribute towards increased cardiovascular risk observed in people with diabetes