Seeing and believing: Observing desistance-focused practice and enduring values in the National Probation Service

This article focuses on the feasibility of using a desistance-focused approach in the National Probation Service (NPS) in the post-Transforming Rehabilitation (TR) context. Findings are drawn from an exploratory study undertaken in one NPS Division, which used triangulation of three data collection methods; observations of one-to-one supervision sessions, documentary analysis and practitioner focus groups. Findings show that practitioners use elements of a desistance-focussed approach, although not exclusively. Values based upon belief in the capacity to change and the need to offer support endure, despite mass organisational upheaval. The article concludes by suggesting that this 'enduring habitus' of probation could be an enabler for a desistance-focused approach but instrumentalism in policy and practice is a significant barrier

Angiotensin II for the Treatment of Vasodilatory Shock

BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843.)Peer reviewe

Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries

Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ΔG for guest binding and the guest’s surface area: the change in ΔG for binding is 0.3 kJ mol–1 Å–2, corresponding to 5 kJ mol–1 for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation. The highest association constant is K = 1.2 × 106 M–1 for cycloundecanone, whose volume is approximately 50% of the cavity volume; for larger C12 and C13 cyclic ketones, the association constant progressively decreases as the guests become too large. For a series of C10 aliphatic ketones differing in shape but not size, ΔG for guest binding showed no correlation with surface area. These guests are close to the volume limit of the cavity (cf. Rebek’s 55% rule), so the association constant is sensitive to shape complementarity, with small changes in guest structure resulting in large changes in binding affinity. The most flexible members of this series (linear aliphatic ketones) did not bind, whereas the more preorganized cyclic ketones all have association constants of 104–105 M–1. A crystal structure of the cage·cycloundecanone complex shows that the guest carbonyl oxygen is directed into a binding pocket defined by a convergent set of CH groups, which act as weak hydrogen-bond donors, and also shows close contacts between the exterior surface of the disc-shaped guest and the interior surface of the pseudospherical cage cavity despite the slight mismatch in shape

An Interconverting Family of Coordination Cages and a meso-Helicate; Effects of Temperature, Concentration, and Solvent on the Product Distribution of a Self-Assembly Process

The self-assembly between a water-soluble bis-bidentate ligand L^18w and Co­(II) salts in water affords three high-spin Co­(II) products: a dinuclear <i>meso</i>-helicate [Co₂(L^18w)₃]­X₄; a tetrahedral cage [Co₄(L^18w)₆]­X₈; and a dodecanuclear truncated-tetrahedral cage [Co₁₂(L^18w)₁₈]­X₂₄ (X = BF₄ or ClO₄). All three products were crystallized under different conditions and structurally characterized. In [Co₂(L^18w)₃]­X₄ all three bridging ligands span a pair of metal ions; in the two larger products, there is a metal ion at each vertex of the Co₄ or Co₁₂ polyhedral cage array with a bridging ligand spanning a pair of metal ions along every edge. All three structural types are known: what is unusual here is the presence of all three from the same reaction. The assemblies <b>Co</b>_<b>2</b>, <b>Co</b>_<b>4</b>, and <b>Co</b>_<b>12</b> are in slow equilibrium (hours/days) in aqueous solution, and this can be conveniently monitored by ¹H NMR spectroscopy because (i) the paramagnetism of Co­(II) disperses the signals over a range of ca. 200 ppm and (ii) the different symmetries of the three species give characteristically different numbers of independent ¹H NMR signals, which makes identification easy. From temperature- and concentration-dependent ¹H NMR studies it is clear that increasing temperature and increasing dilution favors fragmentation to give a larger proportion of the smaller assemblies for entropic reasons. High concentrations and low temperature favor the larger assembly despite the unfavorable entropic and electrostatic factors associated with its formation. We suggest that this arises from the hydrophobic effect: reorganization of several smaller complexes into one larger one results in a smaller proportion of the hydrophobic ligand surface being exposed to water, with a larger proportion of the ligand surface protected in the interior of the assembly. In agreement with this, ¹H NMR spectra in a nonaqueous solvent (MeNO₂) show formation of only [Co₂(L^18w)₃]­X₄ because the driving force for reorganization into larger assemblies is now absent. Thus, we can identify the contributions of temperature, concentration, and solvent on the result of the metal/ligand self-assembly process and have determined the speciation behavior of the <b>Co</b>_<b>2</b>/<b>Co</b>_<b>4</b>/<b>Co</b>_<b>12</b> system in aqueous solution