Acquired Brain Injury and Interventions in the Offender Population: A Systematic Review

Background and Aims: The prevalence of acquired brain injury (ABI) in offender populations appears much higher than in the general population, being estimated at 50% compared to 12%, respectively. Taking into account ABI-related cognitive and social impairments or behavioral changes in forensic treatments might be relevant and may improve treatment outcomes. The aim of the current review is to summarize and integrate the literature on psychological interventions or treatments for consequences of ABI in the forensic setting. Reviewing this literature could provide crucial information for improving treatment options for offenders with ABI, which may contribute to reducing recidivism. Methods: The PubMed/MEDLINE, PsychInfo, CINAHL, COCHRANE, and Web of Science databases were searched for studies in adult offenders with ABI that evaluated the effect of psychological interventions with a focus on ABI-related impairments and recidivism. Results: This review identified four intervention studies that met the inclusion criteria. These included an adult population (≥18-year-old) in a forensic setting (given the focus of the current review on treatment, defined here as an environment in which offenders are treated while being incarcerated or as outpatients), non-pharmacological treatments and were published in English or Dutch between 2005 and 2020. All studies reported some positive effects of the intervention on interpersonal behavior, cognition and recidivism. The aspects of the interventions that seemed most beneficial included personalized treatment and re-entry plans, support for the individual and their environment and psychoeducation about the effects of ABI. Discussion: Although positive effects were reported in the studies reviewed, all studies had methodological limitations in terms of sample size, study design and outcome measures which affects the strength of the evidence. This limits strong conclusions and generalizability to the entire offender population. Conclusion: Despite high prevalence of ABI in offender populations, interventions in forensic settings seldom address the effect of ABI. The few studies that did take ABI into account reported positive effects, but those results should be interpreted with caution. Future studies are warranted, since this does seem an important venue to improve treatment, which could eventually contribute to reducing recidivism

Temperature Dependence of Facet Ridges in Crystal Surfaces

The equilibrium crystal shape of a body-centered solid-on-solid (BCSOS) model on a honeycomb lattice is studied numerically. We focus on the facet ridge endpoints (FRE). These points are equivalent to one dimensional KPZ-type growth in the exactly soluble square lattice BCSOS model. In our more general context the transfer matrix is not stochastic at the FRE points, and a more complex structure develops. We observe ridge lines sticking into the rough phase where thesurface orientation jumps inside the rounded part of the crystal. Moreover, the rough-to-faceted edges become first-order with a jump in surface orientation, between the FRE point and Pokrovsky-Talapov (PT) type critical endpoints. The latter display anisotropic scaling with exponent $z=3$ instead of familiar PT value $z=2$.Comment: 12 pages, 19 figure

Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models

RASopathies, characterized by germline mutations in genes encoding proteins of the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest themselves with a varying severity of intellectual disability. However, it is unclear to what extent they share the same downstream pathophysiology that underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy caused by activating mutations in the HRAS gene. Here we investigated the mechanisms underlying the cognitive deficits of HRas G12V/G12V mice. HRas G12V/G12V mice showed robust upregulation of ERK signaling, neuronal hypertrophy, increased brain volume, spatial learning deficits, and impaired mGluR-dependent long-term depression (LTD). In contrast, long-term potentiation (LTP), which is affected in other RASopathy mouse models was unaffected. Treatment with lovastatin, a HMG-CoA-Reductase inhibitor which has been shown to rescue the behavioral phenotypes of mouse models of NF1 and Noonan syndrome, was unable to restore ERK signaling and the cognitive deficits of HRas G12V/G12V mice. Administration of a potent mitogen-activated protein kinase (MEK) inhibitor rescued the ERK upregulation and the mGluR-LTD deficit of HRas G12V/G12V mice, but failed to rescue the cognitive deficits. Taken together, this study indicates that the fundamental molecular and cellular mechanisms underlying the cognitive aspects of different RASopathies are remarkably distinct, and may require disease specific treatments

In vivo Raman spectroscopy for bladder cancer detection using a superficial Raman probe compared to a nonsuperficial Raman probe

Raman spectroscopy is promising as a noninvasive tool for cancer diagnosis. A superficial Raman probe might improve the classification of bladder cancer, because information is gained solely from the diseased tissue and irrelevant information from deeper layers is omitted. We compared Raman measurements of a superficial to a nonsuperficial probe, in bladder cancer diagnosis. Two-hundred sixteen Raman measurements and biopsies were taken in vivo from at least one suspicious and one unsuspicious bladder location in 104 patients. A Raman classification model was constructed based on histopathology, using a principal-component fed linear-discriminant-analysis and leave-one-person-out cross-validation. The diagnostic ability measured in area under the receiver operating characteristics curve was 0.95 and 0.80, the sensitivity was 90% and 85% and the specificity was 87% and 88% for the superficial and the nonsuperficial probe, respectively. We found inflammation to be a confounder and additionally we found a gradual transition from benign to low-grade to high-grade urothelial carcinoma. Raman spectroscopy provides additional information to histopathology and the diagnostic value using a superficial probe. </p

Rijkswaterstaat:Guardian of the Dutch Delta

Founded in 1798, Rijkswaterstaat, the Dutch government’s agency for infrastructural works, brought flood security, navigable waterways and highways to the Netherlands. It is an iconic institution within Dutch society, best known for its ‘battle against the water’. The Zuiderzee Works (1920–1968) and the Delta Works (1954–1997) brought worldwide acclaim. This chapter tells the story of a humble semi-military organization that developed into a formidable institution of civil engineers with a strong technocratic mission mystique. It also recounts the institutional crisis the agency experienced in the 1970s–1990s when it was too slow to adapt to major sociocultural and political changes. To ride the waves of change, it eventually developed several proactive adaptation strategies and reinvented its mission mystique in managerial terms. Adaptation to climate change now presents another key challenge, for which Rijkswaterstaat will have to develop a new ‘social license to operate’

The effects of high frequency subthalamic stimulation on balance performance and fear of falling in patients with Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Balance impairment is one of the most distressing symptoms in Parkinson's disease (PD) even with pharmacological treatment (levodopa). A complementary treatment is high frequency stimulation in the subthalamic nucleus (STN). Whether STN stimulation improves postural control is under debate. The aim of this study was to explore the effects of STN stimulation alone on balance performance as assessed with clinical performance tests, subjective ratings of fear of falling and posturography.</p> <p>Methods</p> <p>Ten patients (median age 66, range 59–69 years) with bilateral STN stimulation for a minimum of one year, had their anti-PD medications withdrawn overnight. Assessments were done both with the STN stimulation turned OFF and ON (start randomized). In both test conditions, the following were assessed: motor symptoms (descriptive purposes), clinical performance tests, fear of falling ratings, and posturography with and without vibratory proprioceptive disturbance.</p> <p>Results</p> <p>STN stimulation alone significantly (p = 0.002) increased the scores of the Berg balance scale, and the median increase was 6 points. The results of all timed performance tests, except for sharpened Romberg, were significantly (p ≤ 0.016) improved. The patients rated their fear of falling as less severe, and the total score of the Falls-Efficacy Scale(S) increased (p = 0.002) in median with 54 points. All patients completed posturography when the STN stimulation was turned ON, but three patients were unable to do so when it was turned OFF. The seven patients with complete data showed no statistical significant difference (p values ≥ 0.109) in torque variance values when comparing the two test situations. This applied both during quiet stance and during the periods with vibratory stimulation, and it was irrespective of visual input and sway direction.</p> <p>Conclusion</p> <p>In this sample, STN stimulation alone significantly improved the results of the clinical performance tests that mimic activities in daily living. This improvement was further supported by the patients' ratings of fear of falling, which were less severe with the STN stimulation turned ON. Posturography could not be performed by three out of the ten patients when the stimulation was turned OFF. The posturography results of the seven patients with complete data showed no significant differences due to STN stimulation.</p

The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

Contains fulltext : 81280.pdf (publisher's version ) (Open Access)BACKGROUND: Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH), the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. METHODS: We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. RESULTS: A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. CONCLUSION: The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL

An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2−/− γc−/− mouse

The occurrence of metastases is a critical determinant of the prognosis for breast cancer patients. Effective treatment of breast cancer metastases is hampered by a poor understanding of the mechanisms involved in the formation of these secondary tumor deposits. To study the processes of metastasis, valid in vivo tumor metastasis models are required. Here, we show that increased expression of the EGF receptor in the MTLn3 rat mammary tumor cell-line is essential for efficient lung metastasis formation in the Rag mouse model. EGFR expression resulted in delayed orthotopic tumor growth but at the same time strongly enhanced intravasation and lung metastasis. Previously, we demonstrated the critical role of NK cells in a lung metastasis model using MTLn3 cells in syngenic F344 rats. However, this model is incompatible with human EGFR. Using the highly metastatic EGFR-overexpressing MTLn3 cell-line, we report that only Rag2−/−γc−/− mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland. In contrast, in nude and SCID mice, the remaining innate immune cells reduce MTLn3 lung metastasis formation. Furthermore, we confirm this finding with the orthotopic transplantation of the 4T1 mouse mammary tumor cell-line. Thus, we have established an improved in vivo model using a Rag2−/− γc−/− mouse strain together with MTLn3 cells that have increased levels of the EGF receptor, which enables us to study EGFR-dependent tumor cell autonomous mechanisms underlying lung metastasis formation. This improved model can be used for drug target validation and development of new therapeutic strategies against breast cancer metastasis formation