Derived insensitivity:Rule-based insensitivity to contingencies propagates through equivalence

© 2017 Elsevier Inc. Rule-governed behaviours enable rapid acquisition of appropriate and often complex behaviour in novel contexts; however, this capacity can also make individuals insensitive to environmental contingencies. This problem may be exacerbated if rules propagate from one context to another through derived relational responding. Here we assessed whether insensitivity due to rule-following would transfer to stimuli that were never directly associated with that rule, by means of combinatorial entailment. Multiple reinforcement schedules (1A = VR8; 2A = DRL8) were initially presented to two groups, one receiving rules on how to behave to earn as many points as possible, the other not receiving any rule. The participants then completed a matching-to-sample task in which equivalence classes were trained in a one-to-many format (1A ⟵ 1B → 1C; 2A ⟵ 12B → 2C). Finally, the derived stimuli (1C and 2C) were presented in a second multiple-schedule task, where the associated schedules were reversed (1C = DRL8; 2C = VR8), without informing the participants. Results demonstrated that insensitivity transferred to the stimuli set in equivalence for the participants who received rules, while participants who did not receive any rule adapted quicker to the contingencies changes. Results are discussed in relation to behavioural variability and psychological inflexibility that contributes to the development and maintenance of psychological issues

Syntheses, Raman Spectroscopy and Crystal Structures of Alkali Hexa-fluoridorhenates(IV) Revisited

The A2[ReF6] (A = K, Rb and Cs) salts are isotypic and crystallize in the trigonal space group type P\overline{3}m1, adopting the K2[GeF6] structure type. Common to all A2[ReF6] structures are slightly distorted octa­hedral [ReF6]2− anions with an average Re—F bond length of 1.951 (8) Å. In those salts, symmetry lowering on the local [ReF6]2− anions from Oh (free anion) to D3d (solid-state structure) occur. The distortions of the [ReF6]2− anions, as observed in their Raman spectra, are correlated to the size of the counter-cations

Further Improvements of the P. falciparum Humanized Mouse Model

BACKGROUND: It has been shown previously that it is possible to obtain growth of Plasmodium falciparum in human erythrocytes grafted in mice lacking adaptive immune responses by controlling, to a certain extent, innate defences with liposomes containing clodronate (clo-lip). However, the reproducibility of those models is limited, with only a proportion of animals supporting longstanding parasitemia, due to strong inflammation induced by P. falciparum. Optimisation of the model is much needed for the study of new anti-malarial drugs, drug combinations, and candidate vaccines. MATERIALS/METHODS: We investigated the possibility of improving previous models by employing the intravenous route (IV) for delivery of both human erythrocytes (huRBC) and P. falciparum, instead of the intraperitoneal route (IP), by testing various immunosuppressive drugs that might help to control innate mouse defences, and by exploring the potential benefits of using immunodeficient mice with additional genetic defects, such as those with IL-2Rγ deficiency (NSG mice). RESULTS: We demonstrate here the role of aging, of inosine and of the IL-2 receptor γ mutation in controlling P. falciparum induced inflammation. IV delivery of huRBC and P. falciparum in clo-lip treated NSG mice led to successful infection in 100% of inoculated mice, rapid rise of parasitemia to high levels (up to 40%), long-lasting parasitemia, and consistent results from mouse-to-mouse. Characteristics were closer to human infection than in previous models, with evidence of synchronisation, partial sequestration, and receptivity to various P. falciparum strains without preliminary adaptation. However, results show that a major IL-12p70 inflammatory response remains prevalent. CONCLUSION: The combination of the NSG mouse, clodronate loaded liposomes, and IV delivery of huRBC has produced a reliable and more relevant model that better meets the needs of Malaria research

Use of an integrated clinical trial database to evaluate the effect of timing of drotrecogin alfa (activated) treatment in severe sepsis

INTRODUCTION: Several studies have indicated that early identification and treatment of patients with severe sepsis using standard supportive care improves outcomes. Earlier treatment with drotrecogin alfa (activated) (DrotAA) may also improve outcomes in severe sepsis. Using a recently constructed integrated severe sepsis database, our objectives in this study were to describe the influence of baseline clinical characteristics on timing of DrotAA treatment in patients with severe sepsis, to evaluate the efficacy of DrotAA with respect to timing of administration, and to examine the association between early intervention with DrotAA and patient outcomes, using adjustments for imbalances. METHODS: The database comprises data from 4,459 patients with severe sepsis (DrotAA, n = 3,228; placebo, n = 1,231) included in five clinical trials conducted in tertiary care institutions in 28 countries. Placebo data came only from randomized trials, whereas data for the DrotAA group came from randomized (PROWESS) and open-label/observational (ENHANCE) trials. RESULTS: Increased time-to-treatment with DrotAA was significantly associated with more organ dysfunction, greater need of mechanical ventilation, vasopressor use, or recent surgery. Earlier treatment was associated with higher baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Adjusted and unadjusted survival analyses suggested that compared with placebo, DrotAA treatment provided a potential survival benefit, regardless of time to treatment. Survival curves of DrotAA patients treated early compared with those treated late began to separate at 14 days. By 28 days, patients treated earlier had higher survival than those treated later (76.4% versus 73.5%, p = 0.03). Sepsis-induced multiorgan dysfunction was the most common cause of death followed by refractory shock and respiratory failure. Modeling of the treatment effect, as a function of time to treatment, suggested increased benefit with earlier treatment. CONCLUSION: Using an integrated database of five severe sepsis trials and appropriate statistical adjustments to reduce sources of potential bias, earlier treatment with DrotAA seemed to be associated with a lower risk-adjusted mortality than later treatment. These data suggest that earlier treatment with DrotAA may provide most benefit for appropriate patients

Thermal Analysis of Benzotriazolium Perrhenate and Its Implication to Rhenium Metal

The thermal analysis behavior of C6H6N3[ReO4] was studied by simultaneous thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) up to 700 °C under argon. Such analysis afforded rhenium metal, which was characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) spectroscopy. XRD peak broadening due to crystallite size and lattice strain was analyzed by both Williamson-Hall (W-H) and Debye-Scherrer (D-S) methods. Efforts to isolate Re metal from the thermal treatment of benzotriazole (BTA = C6H5N3) with NH4ReO4 and Re2O7 under various atmospheres and temperatures are also reported. The results provide a significant insight into the chemistry of group VII transition metals, investigate the potential use of benzotriazole as a reducing agent for metal productions, and demonstrate a successful convenient method for rhenium metal production, which could be applied to other refractory metals

Cerebral microcirculation is impaired during sepsis: an experimental study

INTRODUCTION: Pathophysiology of brain dysfunction due to sepsis remains poorly understood. Cerebral microcirculatory alterations may play a role; however, experimental data are scarce. This study sought to investigate whether the cerebral microcirculation is altered in a clinically relevant animal model of septic shock. METHODS: Fifteen anesthetized, invasively monitored, and mechanically ventilated female sheep were allocated to a sham procedure (n = 5) or sepsis (n = 10), in which peritonitis was induced by intra-abdominal injection of autologous faeces. Animals were observed until spontaneous death or for a maximum of 20 hours. In addition to global hemodynamic assessment, the microcirculation of the cerebral cortex was evaluated using Sidestream Dark-Field (SDF) videomicroscopy at baseline, 6 hours, 12 hours and at shock onset. At least five images of 20 seconds each from separate areas were recorded at each time point and stored under a random number to be analyzed, using a semi-quantitative method, by an investigator blinded to time and condition. RESULTS: All septic animals developed a hyperdynamic state associated with organ dysfunction and, ultimately, septic shock. In the septic animals, there was a progressive decrease in cerebral total perfused vessel density (from 5.9 ± 0.9 at baseline to 4.8 ± 0.7 n/mm at shock onset, P = 0.009), functional capillary density (from 2.8 ± 0.4 to 2.1 ± 0.7 n/mm, P = 0.049), the proportion of small perfused vessels (from 95 ± 3 to 85 ± 8%, P = 0.02), and the total number of perfused capillaries (from 22.7 ± 2.7 to 17.5 ± 5.2 n/mm, P = 0.04). There were no significant changes in microcirculatory flow index over time. In sham animals, the cerebral microcirculation was unaltered during the study period. CONCLUSIONS: In this model of peritonitis, the cerebral microcirculation was impaired during sepsis, with a significant reduction in perfused small vessels at the onset of septic shock. These alterations may play a role in the pathogenesis of septic encephalopathy

The homotopy type of the loops on (n−1)(n-1)-connected (2n+1)(2n+1)-manifolds

For $n\geq 2$ we compute the homotopy groups of $(n-1)$-connected closed manifolds of dimension $(2n+1)$. Away from the finite set of primes dividing the order of the torsion subgroup in homology, the $p$-local homotopy groups of $M$ are determined by the rank of the free Abelian part of the homology. Moreover, we show that these $p$-local homotopy groups can be expressed as a direct sum of $p$-local homotopy groups of spheres. The integral homotopy type of the loop space is also computed and shown to depend only on the rank of the free Abelian part and the torsion subgroup.Comment: Trends in Algebraic Topology and Related Topics, Trends Math., Birkhauser/Springer, 2018. arXiv admin note: text overlap with arXiv:1510.0519

The nonhuman condition: Radical democracy through new materialist lenses

This Critical Exchange explores the nonhuman condition. It asks: What are the implications of decentering the human subject via a new materialist reading of radical democracy? Does this reading dilute political agency? Or should this be seen, on the contrary, as an invitation for new voices and demands to enter into democratic assemblages? How might engagement with the more-than-human disrupt or extend theories of radical democracy? In our introductory contribution, we engage with the radical democratic human subject and explore new materialist thinking and its challenge to anthropocentrism. We offer a preliminary answer to how democratic agency is reconfigured under the nonhuman condition. While these questions have no final answers, we show that engaging with them opens a fruitful conversation about the limits and content of radical democracy