Search

With the increase in the number of risk assessment tools and clinical algorithms in many areas of science and medicine, this Perspective article provides an overview of research findings that can assist in informing the choice of an instrument for practical use. We take the example of violence risk assessment tools in criminal justice and forensic psychiatry, where there are more than 200 such instruments and their use is typically mandated. We outline 10 key questions that researchers, clinicians and other professionals should ask when deciding what tool to use, which are also relevant for public policy and commissioners of services. These questions are based on two elements: research underpinning the external validation, and derivation or development of a particular instrument. We also recommend some guidelines for reporting drawn from consensus guidelines for research in prognostic models. [ABSTRACT FROM AUTHOR]

We studied the effect of angiotensin (ANG) peptides and their C- and N-terminal fragments, microinjected bilaterally into the hypothalamic paraventricular nucleus (PVN) of male Wistar rats, on arginine vasopressin (AVP) release into the blood and drinking. ANG II (1–8) and the C-terminal ANG III (2–8) at 0.1–100 pmol/200 nl induced a dose-dependent increase in AVP release with a maximum of 26.45±6.0 and 31.86±7.0 pg/ml, respectively, vs 1.6±2.0 pg/ml in vehicle treated controls (P<0.001). The highest dose of ANG II and ANG III also induced drinking responses of 4.3±0.78 and 2.91±0.54 ml water/15 min, respectively. Bilateral pretreatment of the PVN with the AT1 receptor antagonist losartan (4 nmol/200 nl) inhibited ANG II- and ANG III-induced AVP release and drinking. Different doses of the C-terminal ANG IV (3–8), ANG (4–8) or ANG (5–8) peptides did not induce AVP release or drinking. The N-terminal ANG (1–7) peptide induced a dose-dependent increase in AVP release (maximum 8.5±3.5 pg/ml after 100 pmol) but the effect was much less potent than that induced by the same dose of ANG II or ANG III. ANG (1–7) failed to induce a drinking response. Pretreatment of the PVN with losartan or the AT2 receptor antagonist, PD 123177 (4 nmol/200 nl), inhibited the 100 pmol ANG (1–7)-induced AVP release. The N-terminal ANG (1–4) peptide did not affect AVP release or drinking at any dose tested. Our data demonstrate that the C-terminal ANG II (1–8) and ANG III (2–8), but not shorter fragments, can induce AVP release and drinking response via AT1 receptors in the PVN. The N-terminal ANG (1–7) was less potent in stimulating AVP release than ANG II or ANG III and had no influence on drinking. Thus, the presence of both arginine2 and phenylalanine8 in the angiotensin peptide sequence appears to be important to elicit AVP release and drinking from the PVN in vivo. [ABSTRACT FROM AUTHOR]

Graph HT ht (12) Finally, a feature observed at both temperatures is the inward increase in the width of chlorite coronas around olivine. [Extracted from the article]

Serpentinite mud volcanism in the Mariana forearc provides a window into the shallow portions of an active subduction zone. Fluid–rock interactions and related mass transfers into the mantle wedge can be assessed by studying the trace element compositions of slab-derived fluids and serpentinized mantle wedge materials brought to the seafloor by the serpentinite mud volcanoes. We investigated variably serpentinized ultramafic clasts from the Yinazao, Fantangisña, and Asùt Tesoru mud volcanoes recovered on International Ocean Discovery Program Expedition 366 to examine the transfer of fluid-mobile elements (FMEs) from the slab to the wedge. These mud volcanoes sample the slab–wedge interface at depths of ~13–18 km and estimated temperatures of 80–250 °C. Our samples represent the serpentinized forearc and exhibit a multi-phase serpentinization history, as apparent from microfabrics, mineralogy, and in situ major and trace elemental analyses of distinct generations of serpentine. Initial hydration of the forearc mantle occurred under reducing conditions by Si-rich fluids. Early serpentine is characterized by generally high concentrations of Li, Sr, Rb, Cs, and Ba. Subsequent fluid–rock interactions were driven by Si-rich and FME-poor fluids and at later stages by Si- and FME-poor fluids in the mud volcano conduits, the latter of which resulted in the abundant formation of Fe-rich brucite. Iowaite and hematite indicate that less reducing conditions prevailed during the alteration of clasts after their emplacement at the seafloor. Concentrations of B are generally high but our dataset does not allow distinguishing slab- from seawater-derived B. Serpentine from the shallow-sourced Yinazao exhibits high Rb/Cs ratios of ≤37, highest concentrations of Li, but lowest Rb, Sr, Ba, and Cs contents. The serpentinizing fluids were derived from expulsion of sedimentary pore waters and by the breakdown of opal in the subducted sediments. Serpentine at the intermediate-sourced Fantangisña has Rb/Cs ratios of <10, similar Li, Sr, and Ba concentrations as Yinazao, but higher Rb and Cs contents. These patterns likely reflect dewatering and FME-release from clays in the subducted sediments. Fluids at the deeply sourced Asùt Tesoru as well originate from clay-breakdown, but increased concentrations of Rb, Sr, Cs, and Ba are further indicative of beginning dehydration of altered oceanic crust. Including data from the South Chamorro serpentinite mud volcano (18 km slab depth; Kahl et al., 2015, Lithos), we provide a detailed record of slab dehydration reactions at shallow forearc depths and the related mobilization of FMEs as well as their transport into the mantle wedge. Our study demonstrates that slab-derived fluids undergo extensive alteration during the interaction with mantle wedge peridotite. Pore waters from the serpentinite mud volcanoes hence provide incomplete insight into the processes at depth; fluid signatures at the slab–wedge interface as well as their across-forearc changes are best recorded in early hydration products such as serpentine. Unlabelled Image • Fluid-mobile element contents in mantle wedge serpentine are a function of P/T conditions in the slab. • Across-forearc changes in concentrations and ratios imply varying element sources. • Rb/Cs ratios fingerprint fluid and element sources at shallow depths. • We present a continuous record of dehydration reactions in the subducting plate. [ABSTRACT FROM AUTHOR]

BACKGROUND Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. [ABSTRACT FROM AUTHOR]