Evaluating the quality of social work supervision in UK children's services: comparing self-report and independent observations

Understanding how different forms of supervision support good social work practice and improve outcomes for people who use services is nearly impossible without reliable and valid evaluative measures. Yet the question of how best to evaluate the quality of supervision in different contexts is a complicated and as-yet-unsolved challenge. In this study, we observed 12 social work supervisors in a simulated supervision session offering support and guidance to an actor playing the part of an inexperienced social worker facing a casework-related crisis. A team of researchers analyzed these sessions using a customized skills-based coding framework. In addition, 19 social workers completed a questionnaire about their supervision experiences as provided by the same 12 supervisors. According to the coding framework, the supervisors demonstrated relatively modest skill levels, and we found low correlations among different skills. In contrast, according to the questionnaire data, supervisors had relatively high skill levels, and we found high correlations among different skills. The findings imply that although self-report remains the simplest way to evaluate supervision quality, other approaches are possible and may provide a different perspective. However, developing a reliable independent measure of supervision quality remains a noteworthy challenge

Dysregulation of Gene Expression in a Lysosomal Storage Disease Varies between Brain Regions Implicating Unexpected Mechanisms of Neuropathology

The characteristic neurological feature of many neurogenetic diseases is intellectual disability. Although specific neuropathological features have been described, the mechanisms by which specific gene defects lead to cognitive impairment remain obscure. To gain insight into abnormal functions occurring secondary to a single gene defect, whole transcriptome analysis was used to identify molecular and cellular pathways that are dysregulated in the brain in a mouse model of a lysosomal storage disorder (LSD) (mucopolysaccharidosis [MPS] VII). We assayed multiple anatomical regions separately, in a large cohort of normal and diseased mice, which greatly increased the number of significant changes that could be detected compared to past studies in LSD models. We found that patterns of aberrant gene expression and involvement of multiple molecular and cellular systems varied significantly between brain regions. A number of changes revealed unexpected system and process alterations, such as up-regulation of the immune system with few inflammatory changes (a significant difference from the closely related MPS IIIb model), down-regulation of major oligodendrocyte genes even though white matter changes are not a feature histopathologically, and a plethora of developmental gene changes. The involvement of multiple neural systems indicates that the mechanisms of neuropathology in this type of disease are much broader than previously appreciated. In addition, the variation in gene dysregulation between brain regions indicates that different neuropathologic mechanisms may predominate within different regions of a diseased brain caused by a single gene mutation

Two-Photon Imaging of Calcium in Virally Transfected Striate Cortical Neurons of Behaving Monkey

Two-photon scanning microscopy has advanced our understanding of neural signaling in non-mammalian species and mammals. Various developments are needed to perform two-photon scanning microscopy over prolonged periods in non-human primates performing a behavioral task. In striate cortex in two macaque monkeys, cortical neurons were transfected with a genetically encoded fluorescent calcium sensor, memTNXL, using AAV1 as a viral vector. By constructing an extremely rigid and stable apparatus holding both the two-photon scanning microscope and the monkey's head, single neurons were imaged at high magnification for prolonged periods with minimal motion artifacts for up to ten months. Structural images of single neurons were obtained at high magnification. Changes in calcium during visual stimulation were measured as the monkeys performed a fixation task. Overall, functional responses and orientation tuning curves were obtained in 18.8% of the 234 labeled and imaged neurons. This demonstrated that the two-photon scanning microscopy can be successfully obtained in behaving primates

Effects of Neonatal Neural Progenitor Cell Implantation on Adult Neuroanatomy and Cognition in the Ts65Dn Model of Down Syndrome

As much of the aberrant neural development in Down syndrome (DS) occurs postnatally, an early opportunity exists to intervene and influence life-long cognitive development. Recent success using neural progenitor cells (NPC) in models of adult neurodegeneration indicate such therapy may be a viable option in diseases such as DS. Murine NPC (mNPC, C17.2 cell line) or saline were implanted bilaterally into the dorsal hippocampus of postnatal day 2 (PND 2) Ts65Dn pups to explore the feasibility of early postnatal treatment in this mouse model of DS. Disomic littermates provided karyotype controls for trisomic pups. Pups were monitored for developmental milestone achievement, and then underwent adult behavior testing at 14 weeks of age. We found that implanted mNPC survived into adulthood and migrated beyond the implant site in both karyotypes. The implantation of mNPC resulted in a significant increase in the density of dentate granule cells. However, mNPC implantation did not elicit cognitive changes in trisomic mice either neonatally or in adulthood. To the best of our knowledge, these results constitute the first assessment of mNPC as an early intervention on cognitive ability in a DS model

Effect of Dam Emplacement and Water Level Changes on Sublacustrine Geomorphology and Recent Sedimentation in Jackson Lake, Grand Teton National Park (Wyoming, United States)

Dam installation on a deep hydrologically open lake provides the experimental framework necessary to study the influence of outlet engineering and changing base levels on limnogeological processes. Here, high-resolution seismic reflection profiles, sediment cores, and historical water level elevation datasets were employed to assess the recent depositional history of Jackson Lake, a dammed glacial lake located adjacent to the Teton fault in western Wyoming (USA). Prograding clinoforms imaged in the shallow stratigraphy indicate a recent lake-wide episode of delta abandonment. Submerged ∼11–12 m below the lake surface, these Gilbert-type paleo-deltas represent extensive submerged coarse-grained deposits along the axial and lateral margins of Jackson Lake that resulted from shoreline transgression following dam construction in the early 20th century. Other paleo-lake margin environments, including delta plain, shoreline, and glacial (drumlins, moraines) landforms were likewise inundated following dam installation, and now form prominent features on the lake floor. In deepwater, a detailed chronology was established using 137Cs, 210Pb, and reservoir-corrected 14C for a sediment core that spans ∼1654–2019 Common Era (CE). Dam emplacement (1908–1916 CE) correlates with a nearly five-fold acceleration in accumulation rates and a depositional shift towards carbonaceous sediments. Interbedded organic-rich black diatomaceous oozes and tan silts track changes in reservoir water level elevation, which oscillated in response to regional climate and downstream water needs between 1908 and 2019 CE. Chemostratigraphic patterns of carbon, phosphorus, and sulfur are consistent with a change in nutrient status and productivity, controlled initially by transgression-driven flooding of supralittoral soils and vegetation, and subsequently with water level changes. A thin gravity flow deposit punctuates the deepwater strata and provides a benchmark for turbidite characterization driven by hydroclimate change. Because the Teton fault is a major seismic hazard, end-member characterization of turbidites is a critical first step for accurate discrimination of mass transport deposits controlled by earthquakes in more ancient Jackson Lake strata. Results from this study illustrate the influence of dam installation on sublacustrine geomorphology and sedimentation, which has implications for lake management and ecosystem services. Further, this study demonstrates that Jackson Lake contains an expanded, untapped sedimentary archive recording environmental changes in the American West

Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)

In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described

Progress in gene therapy for neurological disorders

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy

Newly recognized quaternary surface faulting and folding peripheral to the new madrid seismic zone, central united states, and implications for restraining bend models of intraplate seismic zones

A newly recognized thrust and nearby asymmetric anticline crop out 40 km north of Memphis, Tennessee, and they deform Eocene through Quaternary strata. These east–west-striking, south-verging structures are peripheral to the New Madrid seismic zone (NMSZ) of central North America, the source of M71 earthquakes in 1811–1812. The thrust dips ∼207 N and has 55 m of throw in Eocene strata. An angular intraformational unconformity indicates most deformation was Eocene. The anticline’s limbs dip 77 N and 227 S and fold Eocene and Pleistocene strata. Pleistocene sediments are dropped at least 4 m into a graben along the fold axis. Holocene sediment is ponded upstream from the fold axis, suggesting Holocene activity. Based on outcrops, well logs, and seismic reflection, we interpret the anticline as a fault-tip fold above a splay of the thrust fault. We interpret these thrusts in the context of a previously published sandbox model of a restraining bend uplift, which we apply here to the Reelfoot Rift fault complex. Using the eastern rift margin as the strike-slip fault of the sandbox model, the periphery of the model uplift has an east– west-striking, south-verging oblique-slip thrust where the actual thrust and anticline crop out. These results suggest that young thrust faults may be common along the periphery of the NMSZ and similar active intraplate restraining bends, that the eastern margin of the Reelfoot Rift may have been a principal strike-slip fault of the restraining bend, and that the seismic zone was active as early as Eocene