Reduced mechanical efficiency in left-ventricular trabeculae of the spontaneously hypertensive rat.

Long-term systemic arterial hypertension, and its associated compensatory response of left-ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left-ventricular trabeculae from SHR-F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR-NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR-F differed little from that of the SHR-NF, both SHR groups performed less stress-length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca(2+) cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension-induced left-ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced

The effect of flexible assertive community treatment in Denmark: a quasi-experimental controlled study

BACKGROUND: Flexible assertive community treatment (FACT) is a community-based treatment model for patients with severe mental illness that has been widely implemented despite little evidence for its effectiveness. We aimed to evaluate the effect of FACT on mental health care outcomes compared with treatment from standard community mental health teams (CMHTs) or assertive community treatment (ACT) teams in Denmark. METHODS: We did a quasi-experimental, propensity-score matched, controlled study in five FACT teams, four ACT teams, and five CMHTs in the Capital Region of Denmark. The FACT teams were established on May 1, 2016 (the index date). Patients were identified through the Danish Psychiatric Register and the study population consisted of all patients receiving care from any of these teams on the index date. Assignment to treatment was based on administrative considerations and was not done by the researchers. Patient data were collected from Danish registers. The primary outcome was analysed in the intention-to-treat population and compared mental health care outcomes (psychiatric admissions and bed days, outpatient contacts, self-harm, coercion, and death by any cause) for patients under the care of CMHTs or ACT teams that were reconfigured to FACT teams (CMHT-FACT or ACT-FACT) with patients who remained under the care of CMHTs and ACT teams. Patients who received FACT were matched using propensity scores with control patients from CMHTs and ACT teams to balance differences in baseline characteristics. FINDINGS: On May 1, 2016, 2034 individuals (887 in the CMHT-FACT group, 887 in the matched CMHT group, 130 in the ACT-FACT group, 130 in the matched ACT group) were enrolled and were followed up from Nov 1, 2016, to Nov 1, 2018. The number of outpatient contacts was higher for patients receiving FACT than for those in the control groups (CMHT-FACT vs CMHT: incidence rate ratio 1·15; 95 % CI 1·10-1·20; ACT-FACT vs ACT: 1·15; 1·03-1·29). Patients receiving FACT had fewer admissions than those in the control groups (CMHT-FACT vs CMHT: 0·84; 0·76-0·92; ACT-FACT vs ACT: 0·71; 0·59-0·85). However, there were no significant differences in total inpatient days, use of coercion, episodes of self-harm, or deaths. INTERPRETATION: To our knowledge, this is the first study to investigate the effect of FACT compared with treatment from a CMHT or ACT team. Our results suggest that FACT can provide a more intensive approach in terms of increased outpatient contacts than CMHT care or ACT. FACT requires further evaluation through randomised controlled trials that include a cost-effectiveness component before wider implementation. FUNDING: Mental Health Services in the Capital Region of Denmark

Calorie Restriction Attenuates Terminal Differentiation of Immune Cells

Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a-CD44locells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b-CD27+cells and correspondingly lower proportions of highly differentiated CD11b+CD27-NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations

Are environmental characteristics in the municipal eldercare, more closely associated with frequent short sick leave spells among employees than with total sick leave: a cross-sectional study

Background: It has been suggested that frequent-, short-term sick leave is associated with work environment factors, whereas long-term sick leave is associated mainly with health factors. However, studies of the hypothesis of an association between a poor working environment and frequent short spells of sick leave are few and results are inconsistent. Therefore, we aimed to explore associations between self-reported psychosocial work factors and workplace-registered frequency and length of sick leave in the eldercare sector. Methods: Employees from the municipal eldercare in Aarhus (N = 2,534) were included. In 2005, they responded to a work environment questionnaire. Sick leave records from 2005 were dichotomised into total sick leave days (0–14 and above 14 days) and into spell patterns (0–2 short, 3–9 short, and mixed spells and 1–3 long spells). Logistic regression models were used to analyse associations; adjusted for age, gender, occupation, and number of spells or sick leave length. Results: The response rate was 76%; 96% of the respondents were women. Unfavourable mean scores in work pace, demands for hiding emotions, poor quality of leadership and bullying were best indicated by more than 14 sick leave days compared with 0–14 sick leave days. For work pace, the best indicator was a long-term sick leave pattern compared with a non-frequent short-term pattern. A frequent short-term sick leave pattern was a better indicator of emotional demands (1.62; 95% CI: 1.1-2.5) and role conflict (1.50; 95% CI: 1.2-1.9) than a short-term non-frequent pattern. Age (= 40 years) statistically significantly modified the association between the 1–3 long-term sick leave spell pattern and commitment to the workplace compared with the 3–9 frequent short-term pattern. Conclusions: Total sick leave length and a long-term sick leave spell pattern were just as good or even better indicators of unfavourable work factor scores than a frequent short-term sick leave pattern. Scores in commitment to the workplace and quality of leadership varied with sick leave pattern and age. Thus, different sick leave measures seem to be associated with different work environment factors. Further studies on these associations may inform interventions to improve occupational health care

Random qubit-states and how best to measure them

We consider the problem of measuring a single qubit, known to have been prepared in either a randomly selected pure state or a randomly selected real pure state. We seek the measurements that provide either the best estimate of the state prepared or maximise the accessible information. Surprisingly, any sensible measurement turns out to be optimal. We discuss the application of these ideas to multiple qubits and higher-dimensional systems

Crystal structures of Λ-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes

The ruthenium complex [Ru(phen)2(dppz)] (where phen is a phenanthroline and dppz a dipyridyl–phenazine ligand) is known as a ‘light switch’ complex because its luminescence in solution is significantly enhanced in the presence of DNA. This property is poised to serve in diagnostic and therapeutic applications, but its binding mode with DNA needs to be elucidated further. Here, we describe the crystal structures of the L enantiomer bound to two oligonucleotide duplexes. The dppz ligand intercalates symmetrically and perpendicularly from the minor groove of the d(CCGGTACCGG)2 duplex at the central TA/TA step, but not at the central AT/AT step of d(CCGGATCCGG)2. In both structures, however, a second ruthenium complex links the duplexes through the combination of a shallower angled intercalation into the C1C2/G9G10 step at the end of the duplex, and semi-intercalation into the G3G4 step of an adjacent duplex. The TA/TA specificity of the perpendicular intercalation arises from the packing of phenanthroline ligands against the adenosine residue

Ab-initio Quantum Enhanced Optical Phase Estimation Using Real-time Feedback Control

Optical phase estimation is a vital measurement primitive that is used to perform accurate measurements of various physical quantities like length, velocity and displacements. The precision of such measurements can be largely enhanced by the use of entangled or squeezed states of light as demonstrated in a variety of different optical systems. Most of these accounts however deal with the measurement of a very small shift of an already known phase, which is in stark contrast to ab-initio phase estimation where the initial phase is unknown. Here we report on the realization of a quantum enhanced and fully deterministic phase estimation protocol based on real-time feedback control. Using robust squeezed states of light combined with a real-time Bayesian estimation feedback algorithm, we demonstrate deterministic phase estimation with a precision beyond the quantum shot noise limit. The demonstrated protocol opens up new opportunities for quantum microscopy, quantum metrology and quantum information processing.Comment: 5 figure

General framework for estimating the ultimate precision limit in noisy quantum-enhanced metrology

The estimation of parameters characterizing dynamical processes is central to science and technology. The estimation error changes with the number N of resources employed in the experiment (which could quantify, for instance, the number of probes or the probing energy). Typically, it scales as 1/N^(1/2). Quantum strategies may improve the precision, for noiseless processes, by an extra factor 1/N^(1/2). For noisy processes, it is not known in general if and when this improvement can be achieved. Here we propose a general framework for obtaining attainable and useful lower bounds for the ultimate limit of precision in noisy systems. We apply this bound to lossy optical interferometry and atomic spectroscopy in the presence of dephasing, showing that it captures the main features of the transition from the 1/N to the 1/N^(1/2) behaviour as N increases, independently of the initial state of the probes, and even with use of adaptive feedback.Comment: Published in Nature Physics. This is the revised submitted version. The supplementary material can be found at http://www.nature.com/nphys/journal/v7/n5/extref/nphys1958-s1.pd

Bayesian Conditioning, the Reflection Principle, and Quantum Decoherence

The probabilities a Bayesian agent assigns to a set of events typically change with time, for instance when the agent updates them in the light of new data. In this paper we address the question of how an agent's probabilities at different times are constrained by Dutch-book coherence. We review and attempt to clarify the argument that, although an agent is not forced by coherence to use the usual Bayesian conditioning rule to update his probabilities, coherence does require the agent's probabilities to satisfy van Fraassen's [1984] reflection principle (which entails a related constraint pointed out by Goldstein [1983]). We then exhibit the specialized assumption needed to recover Bayesian conditioning from an analogous reflection-style consideration. Bringing the argument to the context of quantum measurement theory, we show that "quantum decoherence" can be understood in purely personalist terms---quantum decoherence (as supposed in a von Neumann chain) is not a physical process at all, but an application of the reflection principle. From this point of view, the decoherence theory of Zeh, Zurek, and others as a story of quantum measurement has the plot turned exactly backward.Comment: 14 pages, written in memory of Itamar Pitowsk