A modular approach to prepare enantioenriched cyclobutanes: synthesis of (+)-rumphellaone A

A modular synthesis of enantioenriched polyfunctionalized cyclobutanes was developed that features an 8-aminoquinolinamide directed C–H arylation reaction. The C–H arylation products were derivatized through subsequent decarboxylative coupling processes. This synthetic strategy enabled a 9-step enantioselective total synthesis of the antiproliferative meroterpenoid (+)-rumphellaone A

Chemoselective Alteration of Fluorophore Scaffolds as a Strategy for the Development of Ratiometric Chemodosimeters

Ratiometric sensors generally couple binding events or chemical reactions at a distal site to changes in the fluorescence of a core fluorophore scaffold. However, such approaches are often hindered by spectral overlap of the product and reactant species. We provide a strategy to design ratiometric sensors that display dramatic spectral shifts by leveraging the chemoselective reactivity of novel functional groups inserted within fluorophore scaffolds. As a proof-of-principle, fluorophores containing a borinate (RF620) or silanediol (SiOH2R) functionality at the bridging position of the xanthene ring system are developed as endogenous H2O2 sensors. Both these fluorophores display far-red to near-infrared excitation and emission prior to reaction. Upon oxidation by H2O2 both sensors are chemically converted to tetramethylrhodamine, producing significant (≥66 nm) blue-shifts in excitation and emission maxima. This work provides a new concept for the development of ratiometric probes

A modular approach to prepare enantioenriched cyclobutanes: synthesis of (+)-rumphellaone A

A modular synthesis of enantioenriched polyfunctionalized cyclobutanes was developed that features an 8-aminoquinolinamide directed C–H arylation reaction. The C–H arylation products were derivatized through subsequent decarboxylative coupling processes. This synthetic strategy enabled a 9-step enantioselective total synthesis of the antiproliferative meroterpenoid (+)-rumphellaone A

Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B

(+)-Psiguadial B is a diformyl phloroglucinol meroterpenoid that exhibits antiproliferative activity against the HepG2 human hepatoma cancer cell line. This full account details the evolution of a strategy that culminated in the first enantioselective total synthesis of (+)-psiguadial B. A key feature of the synthesis is the construction of the trans-cyclobutane motif by a Wolff rearrangement with in situ catalytic, asymmetric trapping of the ketene. An investigation of the substrate scope of this method to prepare enantioenriched 8-aminoquinolinamides is disclosed. Three routes toward (+)-psiguadial B were evaluated that featured the following key steps: (1) an ortho-quinone methide hetero-Diels–Alder cycloaddition to prepare the chroman framework, (2) a Prins cyclization to form the bridging bicyclo[4.3.1]decane system, and (3) a modified Norrish–Yang cyclization to generate the chroman. Ultimately, the successful strategy employed a ring-closing metathesis to form the seven-membered ring and an intramolecular O-arylation reaction to complete the polycyclic framework of the natural product

The presence and predictors of complicated grief symptoms in perinatally-bereaved mothers from a bereavement support organization

The present study investigated the presence and possible predictors of complicated grief symptoms in perinatally-bereaved mothers (N = 121) up to 5 years post-bereavement. The presence of complicated grief scores in the clinical range was 12.4%, which is higher than in many other bereaved populations, and the presence of other living children may protect against the development of complicated grief symptoms. The majority of the women were able to negotiate a perinatal loss without developing complicated grief; however, there remains an important group of women who up to 5 years later score in the clinical range for complicated grief symptoms

The DIAMOND Initiative: Implementing Collaborative Care for Depression in 75 Primary Care Clinics

Background: The many randomized trials of the collaborative care model for improving depression in primary care have not described the implementation and maintenance of this model. This paper reports how and the degree to which collaborative care process changes were implemented and maintained for the 75 primary care clinics participating in the DIAMOND Initiative (Depression Improvement Across Minnesota–Offering a New Direction). Methods: Each clinic was trained to implement seven components of the model and participated in ongoing evaluation and facilitation activities. For this study, assessment of clinical process implementation was accomplished via completion of surveys by the physician leader and clinic manager of each clinic site at three points in time. The physician leader of each clinic completed a survey measure of the presence of various practice systems prior to and one and two years after implementation. Clinic managers also completed a survey of organizational readiness and the strategies used for implementation. Results: Survey response rates were 96% to 100%. The systems survey confirmed a very high degree of implementation (with large variation) of DIAMOND depression practice systems (mean of 24.4 ± 14.6%) present at baseline, 57.0 ± 21.0% at one year (P = \u3c0.0001), and 55.9 ± 21.3% at two years. There was a similarly large increase (and variation) in the use of various quality improvement strategies for depression (mean of 29.6 ± 28.1% at baseline, 75.1 ± 22.3% at one year (P = \u3c0.0001), and 74.6 ± 23.0% at two years. Conclusions: This study demonstrates that under the right circumstances, primary care clinics that are prepared to implement evidence-based care can do so if financial barriers are reduced, effective training and facilitation are provided, and the new design introduces the specific mental models, new care processes, and workers and expertise that are needed. Implementation was associated with a marked increase in the number of improvement strategies used, but actual care and outcomes data are needed to associate these changes with patient outcomes and patient-reported care

Self-reported interoceptive deficits in eating disorders: A meta-analysis of studies using the eating disorder inventory

This document is the Accepted Manuscript version of the following article: Paul M. Jenkinson, Lauren Taylor, Keith R. Laws, ‘Self-reported interoceptive deficits in eating disorders: A meta-analysis of studies using the eating disorder inventory’, Journal of Psychosomatic Research, Vol. 110: 38-45, July 2018, under embargo until 19 April 2019. The Version of Record is available online at DOI: https://doi.org/10.1016/j.jpsychores.2018.04.005Objective: An impairment of the ability to sense the physiological condition of the body – interoception – has long been proposed as central to the onset and maintenance of eating disorders. More recent attention to this topic has generally indicated the presence of interoceptive deficits in individuals with an eating disorder diagnosis; however, possible links with specific diagnosis, BMI, age, illness duration, depression, and alexithymia remain unclear from individual studies. This meta-analysis aimed to provide a necessary quantitative overview of self-reported interoceptive deficits in eating disorder populations, and the relationship between these deficits and the previously mentioned factors. Methods: Using a random effects model, our meta-analysis assessed the magnitude of differences in interoceptive abilities as measured using the Eating Disorder Inventory in 41 samples comparing people with eating disorders (n=4308) and healthy controls (n=3459). Follow-up and moderator analysis was conducted, using group comparisons and meta-regressions. Results: We report a large pooled effect size of 1.62 for eating disorders with some variation between diagnostic groups. Further moderator analysis showed that BMI, age and alexithymia were significant predictors of overall effect size. Conclusion: This meta-analysis is the first to confirm that large interoceptive deficits occur in a variety of eating disorders and crucially, in those who have recovered. These deficits may be useful in identifying and distinguishing eating disorders. Future research needs to consider both objective and subjective measures of interoception across different types of eating disorders and may fruitfully examine interoception as a possible endophenotype and target for treatment.Peer reviewe

The SuperCam Remote Sensing Instrument Suite for Mars 2020

International audienceThe Mars 2020 rover, essentially a structural twin of MSL, is being built to a) characterize the geology and history of a new landing site on Mars, b) find and characterize ancient habitable environments, c) cache samples for eventual return to Earth, and d) demonstrate in-situ production of oxygen needed for human exploration. Remote-sensing instrumentation is needed to support the first three of these goals [1]. The SuperCam instrument meets these needs with a range of instrumentation including the highest-resolution remote imaging on the rover, two different techniques for determining mineralogy , and one technique to provide elemental compositions. All of these techniques are co-boresighted, providing rapid comprehensive characterization. In addition, for targets within 7 meters of the rover the laser shock waves brush away the dust, providing cleaner surfaces for analysis. SuperCam will use an advanced version of the AEGIS robotic target selection software