Children with cerebral palsy: severity and trends over time

Increasingly, more very-low-birthweight infants in the developed world are now expected to survive the neonatal period than was previously the case. There are concerns that there may be a related increase in the number of infants developing severe sensorimotor impairments. Pooled data from five registers contributing to the UK Network of Cerebral Palsy Registers, Surveys and Databases were used to identify patterns of motor impairment in relation to additional impairments and to birthweight, and to assess whether prevalence of cerebral palsy (CP) by birthweight and by severity of motor impairment had changed over time. Low-birthweight infants are at greater risk of developing CP than larger-birthweight babies. The CP rate amongst children with birthweights <2500 g was significantly higher at 16 per 1000 livebirths [95% confidence interval (CI) 14.9, 16.2] than 1.2 per 1000 livebirths [95% CI 11, 1.2] for normal-birthweight children. Despite being at greater risk of developing CP, smaller-birthweight babies are proportionately less likely to develop the most severe forms of motor impairment. Of those born weighing ≥2500 g, 23% compared with 15% weighing <1000 g (P < 0.001) were in the most severely motor impaired group. Severe motor impairment is associated with higher levels of additional impairments. CP rates for each motor impairment group in the 1990s were similar to those in the late 1970s. Rates of CP among infants born below normal birthweight are high but have decreased over time. The CP rate for infants weighing 1000–1499 g at birth decreased from around 180 per 1000 livebirths in 1979 to around 50 per 1000 livebirths from the early 1990s onwards.

Systemic Family Therapy for Families who have Experienced Trauma: A Randomised Controlled Trial

This paper describes a randomised controlled trial (RCT) investigation of the added value of systemic family therapy (SFT) over individually focused cognitive behavioural therapy (CBT) for families in which one or more members has suffered trauma and been referred to a community-based psychotherapy centre. The results illustrate how an apparently robust design can be confounded by high attrition rates, low average number of therapeutic sessions and poor protocol adherence. The paper highlights a number of general and specific lessons regarding the resources and processes involved that can act as a model for those planning to undertake studies of this type and scope. A key message is that the challenges of conducting RCTs in ‘real world’ settings should not be underestimated. The wider implications in relation to the place of RCTs within the creation of the evidence base for complex psycho-social interventions is discussed and the current movement towards a phased mixed-methods approach, including the appropriate use of RCTs, which some might argue is a return to the original vision of evidence-based practice (EBP), is affirmed.

Differential expression of steroid 5 alpha-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

The biological role of steroid 5 alpha-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor beta 1 (TGFB1), endothelin (EDN1), TGF alpha (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 mu M). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors. Endocrine-Related Cancer (2010) 17 757-770

Childhood Trauma and Hippocampal and Amygdalar Volumes in First-Episode Psychosis

Objective: A history of childhood trauma is common in individuals who later develop psychosis. Similar neuroanatomical abnormalities are observed in people who have been exposed to childhood trauma and people with psychosis. However, the relationship between childhood trauma and such abnormalities in psychosis has not been investigated. This study aimed to explore the association between the experience of childhood trauma and hippocampal and amygdalar volumes in a first-episode psychosis (FEP) population. Methods: The study employed an observational retrospective design. Twenty-one individuals, who had previously undergone magnetic resonance imaging procedures as part of the longitudinal Northern Ireland First-Episode Psychosis Study, completed measures assessing traumatic experiences and were included in the analysis. Data were subject to correlation analyses (rand rob). Potential confounding variables (age at FEP and delay to scan from recruitment) were selected a priori for inclusion in multiple regression analyses. Results: There was a high prevalence of lifetime (95%) and childhood (76%) trauma in the sample. The experience of childhood trauma was a significant predictor of left hippocampal volume, although age at FEP also significantly contributed to this model. There was no significant association between predictor variables and right hippocampal volume. The experience of childhood trauma was a significant predictor of right and total amygdalar volumes and the hippocampal/amygdalar complex volume as a whole. Conclusions: The findings indicate that childhood trauma is associated with neuroanatomical measures in FEP. Future research controlling for childhood traumatic experiences may contribute to explaining brain morphology in people with psychosis.

Conceptual and Perceptual Priming and Dissociation in Chronic Posttraumatic Stress Disorder.

Cognitive models of posttraumatic stress disorder (PTSD) assert that memory processes play a significant role in PTSD (see e.g., Ehlers & Clark, 2000). Intrusive reexperiencing in PTSD has been linked to perceptual processing of trauma-related material with a corresponding hypothesized lack of conceptual processing. In an experimental study that included clinical participants with and without PTSD (N = 50), perceptual priming and conceptual priming for trauma-related, general threat, and neutral words were investigated in a population with chronic trauma-induced complaints as a result of the Troubles in Northern Ireland. The study used a new version of the word-stem completion task (Michael, Ehlers, & Halligan, 2005) and a word-cue association task. It also assessed the role of dissociation in threat processing. Further evidence of enhanced perceptual priming in PTSD for trauma stimuli was found, along with evidence of lack of conceptual priming for such stimuli. Furthermore, this pattern of priming for trauma-related words was associated with PTSD severity, and state dissociation and PTSD group made significant contributions to predicting perceptual priming for trauma words. The findings shed light on the importance of state dissociation in trauma-related information processing and posttraumatic symptoms.

Intravenous tolerance effectively overcomes enhanced pro-inflammatory responses and EAE severity in the absence of IL-12 receptor signaling

Intravenous (i.v.) administration of autoantigen effectively induces Ag-specific tolerance against experimental autoimmune encephalomyelitis (EAE). We and others have shown enhanced EAE severity in mice lacking IL-12 or its receptor, strongly suggesting an immunoregulatory effect of IL-12 signaling. To examine the role of IL-12 responsiveness in autoantigen-induced tolerance in EAE, we administered autoantigen i.v. in two distinct treatment regimes to wildtype and IL-12Rβ2(-/-) mice, immunized to develop EAE. Administration at the induction phase suppressed EAE in wildtype and IL-12Rβ2(-/-) mice however the effect was somewhat less potent in the absence of IL-12Rβ2. Expression of pro-inflammatory cytokines such as IFN-γ, IL-17 and IL-2, was inhibited in wild-type tolerized mice but less so in IL-12Rβ2(-/-) mice. I.v. antigen was also effective in suppressing disease in both genotypes when given during the clinical phase of disease with similar CNS inflammation, demyelination and peripheral inflammatory cytokine profiles observed in both genotypes. There was however a mild impact of a lack of IL-12 signaling on Treg induction during tolerance induction compared to WT mice in this treatment regime. These findings show that the enhanced severity of EAE that occurs in the absence of IL-12 signaling can be effectively overcome by i.v. autoantigen, indicating that this therapeutic effect is not primarily mediated by IL-12 and that i.v. tolerance could be a powerful approach in suppressing severe and aggressive MS.

Severity staging by early features of age-related maculopathy exhibits weak relationships with functional deficits on SWS grating acuity

To examine the relationship between short-wavelength-sensitive (SWS) resolution acuity and epidemiologically defined stages of early age-related maculopathy (ARM).