Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean=35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.Molecular Psychiatry advance online publication, 15 April 2014; doi:10.1038/mp.2014.33.

Improved contact load-bearing capacity of ultra-fine grained titanium : Multilayering and grading

The contact load-bearing response and surface damage resistance of multilayered hierarchical structured (MHSed) titanium were determined and compared to monolithic nanostructured titanium. The MHS structure was formed by combining cryorolling with a subsequent Surface Mechanical Attrition Treatment (SMAT) producing a surface structure consisted of an outer amorphous layer containing nanocrystals, an inner nanostructured layer and finally an ultra-fine grained core. The combination of a hard outer layer, a gradual transition layer and a compliant core results in reduced indentation depth, but a deeper and more diffuse sub-surface plastic deformation zone, compared to the monolithic nanostructured Ti. The redistribution of surface loading between the successive layers in the MHS Ti resulted in the suppression of cracking, whereas the monolithic nanograined (NG) Ti exhibited sub-surface cracks at the boundary of the plastic strain field. Finite element models with discrete layers and mechanically graded layersrepresenting the MHS system confirmed the absence of cracking and revealed a 38% decrease in shear stress in the sub-surface plastic strain field, compared to the monolithic NG Ti. Further, the mechanical gradation achieves a more gradual stress distribution which mitigates the interface failure and increases the interfacial toughness, thus providing strong resistance to loading damage. © 2014 Elsevier Ltd.

Prosecutors’ perceptions on improving child witness interviews about abuse

This edited volume reviews the latest research on investigative interviewing in order to provide insights on the psychological processes of the person being interviewed as well as to offer guidelines for conducting credible and useful ...

Witness recall across repeated interviews in a case of repeated abuse.

In this illustrative case study we examine the three forensic interviews of a girl who experienced repeated sexual abuse from ages 7 to 11. She disclosed the abuse after watching a serialized television show that contained a storyline similar to her own experience. This triggered an investigation that ended in successful prosecution of the offender. Because this case involved abuse that was repeated on a weekly basis for 4 years we thus investigated the degree to which the child's narrative reflected specific episodes or generic accounts, and both the interviewer's and child's attempts to elicit and provide, respectively, specific details across the 3 interviews collected in a 1 month period. Across the 3 interviews, the child's account was largely generic, yet on a number of occasions she provided details specific to individual incidents (episodic leads) that could have been probed further. As predicted: earlier interviews were characterized more by episodic than generic prompts and the reverse was true for the third interview; the child often responded using the same style of language (episodic or generic) as the interviewer; and open questions yielded narrative information. We discuss the importance of adopting children's words to specify occurrences, and the potential benefits of permitting generic recall in investigative interviews on children's ability to provide episodic leads. Despite the fact that the testimony was characterized by generic information about what usually happened, rather than specific episodic details about individual occurrences, this case resulted in successful prosecution.

Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean=35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.

Dynamic weight-bearing assessment of pain in knee osteoarthritis: a reliability and agreement study

Purpose: To evaluate the reliability, agreement and smallest detectable change in a measurement instrument for pain and function in knee osteoarthritis; the Dynamic weight-bearing Assessment of Pain (DAP). Methods: The sample size was set to 20 persons, recruited from the outpatient osteoarthritis clinic at Frederiksberg Hospital, Copenhagen. Two physiotherapists tested all participants during two visits; at the first visit, one single DAP (including four scores) was conducted by rater one; at the second visit, DAP was conducted by both raters one and two in randomized order with concealed allocation. The time interval was approximately 1.5 h. Measurement error was estimated by standard error of measurement (SEM). The intra- and inter-rater reliability was estimated by Intra-class Correlation Coefficients for agreement based on a two-way ANOVA with random effects (single measures ICC 2.1). Smallest detectable change (SDC) and limits of agreement were calculated.Results: The pain score showed excellent reliability in terms of ICC (intra-rater 0.93, CI 0.83–0.97, inter-rater 0.91, CI 0.78–0.96), low SEM (intra-rater 0.70, inter-rater 0.86, on a scale from 0 to 10), and acceptable SDC for intra-rater test (1.95). The three knee bend scores all had ICC above 0.50, showing fair-to-good reliability. None of the knee bend scores showed acceptable SEM and SDC. Conclusions: The reproducibility of the DAP pain score meets the demands for use in clinical practice and research. The total knee bend could be useful for motivational purpose in clinical use. Testing of other psychometric properties of the DAP is pending.

Were the National Socialists a Völkisch Party? Paganism, Christianity, and the Nazi christmas

A trend in studies about National Socialism and religion in recent years argues for a deliberate distinction between the Nazi Party (NSDAP) and the antisemitic völkisch movement of nineteenth-century Germany. This article challenges that contention. Several researchers have published comprehensive studies on the heterogeneous nature of Christian responses to the Nazis, but a comparable approach looking at how the Nazis viewed religion has not yet been undertaken. A study of the latter type is certainly necessary, given that one of the consistent features of the völkisch movement was its diversity. As Roger Griffin has argued, a “striking feature of the sub-culture . . . was just how prolific and variegated it was . . . [T]he only denominator common to all was the myth of national rebirth.” In short, the völkisch movement contained a colorful, varied, and often bewildering range of religious beliefs.

Altered response of the anterolateral abdominal muscles to simulated weight-bearing in subjects with low back pain

An important aspect of neuromuscular control at the lumbo-pelvic region is stabilization. Subjects with low back pain (LBP) have been shown to exhibit impairments in motor control of key muscles which contribute to stabilization of the lumbo-pelvic region. However, a test of automatic recruitment that relates to function has been lacking. A previous study used ultrasound imaging to show that healthy subjects automatically recruited the transversus abdominis (TrA) and internal oblique (IO) muscles in response to a simulated weight-bearing task. This task has not been investigated in subjects with LBP. The aim of this study was to compare the automatic recruitment of the abdominal muscles among subjects with and without LBP in response to the simulated weight-bearing task. Twenty subjects with and without LBP were tested. Real-time ultrasound imaging was used to assess changes in thickness of the TrA and internal oblique IO muscles as well as lateral movement ("slide") of the anterior fascial insertion of the TrA muscle. Results showed that subjects with LBP showed significantly less shortening of the TrA muscle (P < 0.0001) and greater increases in thickness of the IO muscle (P = 0.002) with the simulated weight-bearing task. There was no significant difference between groups for changes in TrA muscle thickness (P = 0.055). This study provides evidence of changes in motor control of the abdominal muscles in subjects with LBP. This test may provide a functionally relevant and non-invasive method to investigate the automatic recruitment of the abdominal muscles in people with and without LBP.