Effects of standard training in the use of closed-circuit televisions in visually impaired adults: design of a training protocol and a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Reading problems are frequently reported by visually impaired persons. A closed-circuit television (CCTV) can be helpful to maintain reading ability, however, it is difficult to learn how to use this device. In the Netherlands, an evidence-based rehabilitation program in the use of CCTVs was lacking. Therefore, a standard training protocol needed to be developed and tested in a randomized controlled trial (RCT) to provide an evidence-based training program in the use of this device.</p> <p>Methods/Design</p> <p>To develop a standard training program, information was collected by studying literature, observing training in the use of CCTVs, discussing the content of the training program with professionals and organizing focus and discussion groups. The effectiveness of the program was evaluated in an RCT, to obtain an evidence-based training program. Dutch patients (n = 122) were randomized into a treatment group: normal instructions from the supplier combined with training in the use of CCTVs, or into a control group: instructions from the supplier only. The effect of the training program was evaluated in terms of: change in reading ability (reading speed and reading comprehension), patients' skills to operate the CCTV, perceived (vision-related) quality of life and tasks performed in daily living.</p> <p>Discussion</p> <p>The development of the CCTV training protocol and the design of the RCT in the present study may serve as an example to obtain an evidence-based training program. The training program was adjusted to the needs and learning abilities of individual patients, however, for scientific reasons it might have been preferable to standardize the protocol further, in order to gain more comparable results.</p> <p>Trial registration</p> <p><url>http://www.trialregister.nl</url>, identifier: NTR1031</p

“Excellence R Us”: university research and the fetishisation of excellence

The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship

When light hurts: Comparative Morphometry of Human Brainstem in Traumatic Photalgia

Traumatic brain injury is an increasingly common affliction, although many of its serious repercussions are still underappreciated. A frequent consequence is the development of light-induced pain, or ‘photalgia’, which can often lead to prolonged debilitation. The mechanism underlying the sensitivity to light, however, remains unresolved. Since tissue oedema (swelling) is a common feature of traumatic brain injury, we propose that the brainstem oedema, in particular, might sensitize the brainstem trigeminal complex to signals from ocular mechanisms activated in bright light. To assess this hypothesis, we ran high-resolution Magnetic Resonance Imaging of the brainstems of concussion groups with mild and severe photalgia, without photalgia, and healthy controls. The 3D configuration of the brainstem was determined by Tensor-Based Morphometry (TBM) for each participant. The TBM revealed significant deviations in the brainstem morphology of all concussion groups, with a characteristic signature for each group. In particular, concussion without photalgia showed bilateral expansion at the pontine/medulla junction, whereas concussion with photalgia showed mid-pontine shrinkage, consistent with degeneration of nuclei of the trigeminal complex. These results support the hypothesis that brainstem shrinkage/degeneration represents a morphological substrate of the photalgic sensitization of the trigeminal pathway

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

A Blast Wave from the 1843 Eruption of Eta Carinae

Very massive stars shed much of their mass in violent precursor eruptions as luminous blue variables (LBVs) before reaching their most likely end as supernovae, but the cause of LBV eruptions is unknown. The 19th century eruption of Eta Carinae, the prototype of these events, ejected about 12 solar masses at speeds of 650 km/s, with a kinetic energy of almost 10^50 ergs. Some faster material with speeds up to 1000-2000 km/s had previously been reported but its full distribution was unknown. Here I report observations of much faster material with speeds up to 3500-6000 km/s, reaching farther from the star than the fastest material in earlier reports. This fast material roughly doubles the kinetic energy of the 19th century event, and suggests that it released a blast wave now propagating ahead of the massive ejecta. Thus, Eta Car's outer shell now mimics a low-energy supernova remnant. The eruption has usually been discussed in terms of an extreme wind driven by the star's luminosity, but fast material reported here suggests that it was powered by a deep-seated explosion rivalling a supernova, perhaps triggered by the pulsational pair instability. This may alter interpretations of similar events seen in other galaxies.Comment: 10 pages, 3 color figs, supplementary information. Accepted by Natur

Context-Dependent Dual Role of SKI8 Homologs in mRNA Synthesis and Turnover

Eukaryotic mRNA transcription and turnover is controlled by an enzymatic machinery that includes RNA polymerase II and the 3′ to 5′ exosome. The activity of these protein complexes is modulated by additional factors, such as the nuclear RNA polymerase II-associated factor 1 (Paf1c) and the cytoplasmic Superkiller (SKI) complex, respectively. Their components are conserved across uni- as well as multi-cellular organisms, including yeast, Arabidopsis, and humans. Among them, SKI8 displays multiple facets on top of its cytoplasmic role in the SKI complex. For instance, nuclear yeast ScSKI8 has an additional function in meiotic recombination, whereas nuclear human hSKI8 (unlike ScSKI8) associates with Paf1c. The Arabidopsis SKI8 homolog VERNALIZATION INDEPENDENT 3 (VIP3) has been found in Paf1c as well; however, whether it also has a role in the SKI complex remains obscure so far. We found that transgenic VIP3-GFP, which complements a novel vip3 mutant allele, localizes to both nucleus and cytoplasm. Consistently, biochemical analyses suggest that VIP3–GFP associates with the SKI complex. A role of VIP3 in the turnover of nuclear encoded mRNAs is supported by random-primed RNA sequencing of wild-type and vip3 seedlings, which indicates mRNA stabilization in vip3. Another SKI subunit homolog mutant, ski2, displays a dwarf phenotype similar to vip3. However, unlike vip3, it displays neither early flowering nor flower development phenotypes, suggesting that the latter reflect VIP3's role in Paf1c. Surprisingly then, transgenic ScSKI8 rescued all aspects of the vip3 phenotype, suggesting that the dual role of SKI8 depends on species-specific cellular context

1H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice

BACKGROUND: Human medulloblastomas exhibit diverse molecular pathology. Aberrant hedgehog signalling is found in 20-30% of human medulloblastomas with largely unknown metabolic consequences. METHODS: Transgenic mice over-expressing smoothened (SMO) receptor in granule cell precursors with high incidence of exophytic medulloblastomas were sequentially followed up by magnetic resonance imaging (MRI) and characterised for metabolite phenotypes by ¹H MR spectroscopy (MRS) in vivo and ex vivo using high-resolution magic angle spinning (HR-MAS) ¹H MRS. RESULTS: Medulloblastomas in the SMO mice presented as T₂ hyperintense tumours in MRI. These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice. In contrast, ¹H MRS metabolite concentrations in normal appearing cerebellum of the SMO mice were not different from those in the WT mice. Macromolecule and lipid ¹H MRS signals in SMO medulloblastomas were not different from those detected in the cerebellum of WT mice. The HR-MAS analysis of SMO medulloblastomas confirmed the in vivo ¹H MRS metabolite profiles, and additionally revealed that phosphocholine was strongly elevated in medulloblastomas accounting for the high in vivo CCM. CONCLUSIONS: These metabolite profiles closely mirror those reported from human medulloblastomas confirming that SMO mice provide a realistic model for investigating metabolic aspects of this disease. Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas. The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours

Using appreciative inquiry to develop, implement and evaluate a multi-organisation ‘Cultivating Compassion’ programme for health professionals and support staff

The ‘Cultivating Compassion’ project was developed in response to a research and innovation call relating to compassion training for National Health Service staff in the South East of England. The project aims included the following: the use of Appreciative Inquiry to develop, implement and evaluate a sustainable and evidence-based programme of compassion awareness training through engaging with a diverse group of health professionals and support staff; an evaluation of a ‘train the trainers’ approach; and an evaluation of ‘compassion lead’ roles and a multi-modal compassion toolkit. The project team included academics from two universities and one medical school, NHS staff from three separate organisations and service users. The participants recruited to the study included doctors, nurses, receptionists, chaplains and others working in close contact with service users from within four NHS organisations in the South East of England. The main findings from the project using thematic analysis from participant focus groups and interviews identified project enablers and inhibitors, the value of project resources, and shifts in perspectives. Project conclusions highlighted the importance of effective senior-level support and organisational leadership in cultivating compassion within a healthcare organisation and the importance of the integration of compassion-promoting resources within existing staff development initiatives

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition