Diagnostic value of the Dutch version of the MCclean Screening instrument for BPD (MSI-BPD)

Borderline personality disorder (BPD) often goes unrecognized, and therefore a short but accurate screening tool is desired. The present study investigated the psychometric properties of the 10-item McLean Screening Instrument for BPD (MSI-BPD) in 159 well-diagnosed female participants. The MSI-BPD showed excellent internal consistency (alpha = .90). When compared to BPD diagnoses based on a structured clinical interview (SCID-II), the MSI-BPD showed substantial congruent validity (receiver operating characteristic area under the curve = 0.96). The cutoff point proposed by the developers of the MSI-BPD (7 or more) showed high specificity (.96) and good sensitivity (.71). The optimal cutoff point in the present study (5 or more) showed somewhat lower specificity (.86), but importantly better sensitivity (.94). Taken together, the Dutch version of the MSI-BPD demonstrated good psychometric properties for a screening tool

Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation

Leucine-rich repeat kinase 2 (LRRK2) kinase activity is increased in several pathogenic mutations, including the most common mutation, G2019S, and is known to play a role in Parkinson’s disease (PD) pathobiology. This has stimulated the development of potent, selective LRRK2 kinase inhibitors as one of the most prevailing disease-modifying therapeutic PD strategies. Although several lines of evidence support beneficial effects of LRRK2 kinase inhibitors, many questions need to be answered before clinical applications can be envisaged. Using six different LRRK2 kinase inhibitors, we show that LRRK2 kinase inhibition induces LRRK2 dephosphorylation and can reduce LRRK2 protein levels of overexpressed wild type and G2019S, but not A2016T or K1906M, LRRK2 as well as endogenous LRRK2 in mouse brain, lung and kidney. The inhibitor-induced reduction in LRRK2 levels could be reversed by proteasomal inhibition, but not by lysosomal inhibition, while mRNA levels remained unaffected. In addition, using LRRK2 S910A and S935A phosphorylation mutants, we show that dephosphorylation of these sites is not required for LRRK2 degradation. Increasing our insight in the molecular and cellular consequences of LRRK2 kinase inhibition will be crucial in the further development of LRRK2-based PD therapies

An Investigation of the Seismic Response of Earthen Levees with Cutoff Walls with a Focus on the Development of a High Performance Cutoff Wall Material.

In recent years, flood protection systems across the nation have undergone extensive investigation into their current state and adequacy regarding various potential hazards. These investigations have revealed that 1) many existing levees are vulnerable to excessive under- and through-seepage due to the insufficient state or length of their cutoff walls, and 2) seismic activity poses serious risks to many existing levees. Traditional cutoff walls (e.g. slurry-type walls and steel sheet pile walls) have a variety of shortcomings, particularly for levees in seismic regions. This project investigates the feasibility of using a new cutoff wall material that overcomes many of the shortcomings associated with traditional cutoff wall materials. The proposed cutoff wall material is from a family of high performance fiber-reinforced cementitious materials called Engineered Cementitious Composites (ECC). ECC possesses several characteristics that make it ideal for use as a cutoff wall material in seismic regions, including high tensile ductility and small crack width, among others. The initial portion of this study focuses on characterizing the dynamic response of levees with conventional cutoff walls. Two sets of parametric analyses are conducted to investigate how the presence of a cutoff wall affects the dynamic response of a levee and what type of demands are placed on the cutoff wall during the seismic event. One set of analyses is conducted for levees founded on non-liquefiable soils and the other is for levees founded on liquefiable soils. In collaboration with materials science researchers, an ECC material is then tailored for use in the construction of levee cutoff walls. The results of materials testing on the resulting candidate mix design are then used as input in further numerical modeling, in which the dynamic response of levees with ECC cutoff walls is investigated. These analyses are used to assess the feasibility of the candidate mix design. Conclusions regarding the feasibility of using such a material for levee cutoff walls are presented, with recommendations for a candidate ECC mix. Also, revisions to existing levee seismic design guidelines are proposed, based on the results of the parametric analyses of the dynamic response of levees with conventional cutoff wallsPHDCivil EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/110458/1/ajimlobb_1.pd

Schema therapy for chronic depression: Results of a multiple single case series

Background and Objectives: The aim of this study was to test the effects of individual schema therapy (ST) for patients with chronic depression. Methods: Using a multiple-baseline single case series design, patients with chronic major depressive disorder (N = 25) first entered a 6 to 24 weeks baseline phase; this phase functioned as a no-treatment control condition. Then, patients started a 12 week exploration phase during which symptoms and underlying schemas were explored; this phase functioned as an attention control condition. Next, patients received up to 65 sessions of individual ST. The Beck Depression Inventory II (BDI-II) and the Quick Inventory of Depressive Symptomatology (QIDS) were the primary outcome measures. The BDI-II was assessed once a week during all phases of the study resulting in 100 repeated assessments per participant on average. Mixed regression analysis was used to contrast change in symptoms during the intervention with change in symptoms during the baseline and exploration control phases. Results: When compared to the no-treatment control period, the intervention had a significant, large effect on depressive symptoms (Cohen’s d BDI-II = 1.30; Cohen’s d QIDS = 1.22). Effects on secondary continuous outcomes were moderate to large. Limitations: The small sample size and lack of a control group. Conclusions: These findings provide evidence that ST might be an effective treatment for patients with chronic depression