Determinants of infant mortality and representation in bioarchaeological samples : a review

ACKNOWLEDGEMENTS This article is dedicated to the memory of Alistair D. E. Muir (1972 - 2020). This research was partly funded by a British Academy grant GP2\190224. The authors thank the reviewers for their feedback which has improved this manuscript.Peer reviewedPostprin

Basic Salts with »Very Short« Hydrogen Bonds; the Crystal Structure of a-Picoline-N-oxide Hemihydrochloride Sesquihydrate (Dunlop\u27s Salt)

Type A acid salts of many simple carboxylic acids (HX) crystallise with anions, XHx-, which are symmetrical and which contain »very short« OHO-bonds with O . .. 0 less than 250 pm. Such compounds also reveal anomalous IR spectra. The Glasgow work on such crystal structures has benefited from a long collaboration with Hadzi\u27s spectroscopic group at Ljubljana. The importance of such joint studies in helping the understanding of strong hydrogen bonding is discussed. Some organic bases form analogous basic salts, which have similarly anomalous spectra. An example, discovered by Hadzi in 1962, is the hemihydrobromide of a.-picoline-N-oxide, B · 1/2HBr, where B = CoH7NO, for which he predicted the formula BHB+ Br-. Preliminary X-ray work confirmed this and the presence of a »very short« OHO-bond. Hitherto unpublished crystallographic work is summarised. Dunlop\u27s salt is the sesquihydrated hemihydrochloride of the same base. A careful X-ray study has been made (1040 reflexions; R = 3.70/o): B · 1/2HCl · 3/2H20 has a structure corresponding to BHB+ c1- · 3H20; the cation lies across a centre of symmetry, with O ... O = 241.4(3) pm. At one stage the salt was supposed to include a symmetrical ClHc1- anion; but our more precise work shows the anion to be c1- ... H-OH (or HO-H ... en symmetrised by disorder across a twofold axis of the crystal, with c1- ... O = = 297(1) pm. The spectrum of DSALT is almost identical with that of the hemihydrobromide

Stakeholders in the selection of digital material for preservation: relationships, responsibilities, and influence

Selecting digital material for preservation in libraries, archives, and museums is a necessary task but has not been widely examined, although the nature of digital material challenges traditional methods of selecting. This article examines the social context of selection in institutions, in which the responsibilities of stakeholders and relationships between them can affect the material chosen for preservation by practitioners. A range of stakeholders is identified; relationships between practitioners, information technology staff, and sources of material are found to be crucial. The influence of senior managers is important in providing a mandate and encouraging shared working and networks of expertise

Basic Salts with »Very Short« Hydrogen Bonds; the Crystal Structure of a-Picoline-N-oxide Hemihydrochloride Sesquihydrate (Dunlop\u27s Salt)

Type A acid salts of many simple carboxylic acids (HX) crystallise with anions, XHx-, which are symmetrical and which contain »very short« OHO-bonds with O . .. 0 less than 250 pm. Such compounds also reveal anomalous IR spectra. The Glasgow work on such crystal structures has benefited from a long collaboration with Hadzi\u27s spectroscopic group at Ljubljana. The importance of such joint studies in helping the understanding of strong hydrogen bonding is discussed. Some organic bases form analogous basic salts, which have similarly anomalous spectra. An example, discovered by Hadzi in 1962, is the hemihydrobromide of a.-picoline-N-oxide, B · 1/2HBr, where B = CoH7NO, for which he predicted the formula BHB+ Br-. Preliminary X-ray work confirmed this and the presence of a »very short« OHO-bond. Hitherto unpublished crystallographic work is summarised. Dunlop\u27s salt is the sesquihydrated hemihydrochloride of the same base. A careful X-ray study has been made (1040 reflexions; R = 3.70/o): B · 1/2HCl · 3/2H20 has a structure corresponding to BHB+ c1- · 3H20; the cation lies across a centre of symmetry, with O ... O = 241.4(3) pm. At one stage the salt was supposed to include a symmetrical ClHc1- anion; but our more precise work shows the anion to be c1- ... H-OH (or HO-H ... en symmetrised by disorder across a twofold axis of the crystal, with c1- ... O = = 297(1) pm. The spectrum of DSALT is almost identical with that of the hemihydrobromide

Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: Results from the UK7T study

Introduction We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's “Travelling Heads” study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5–3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. Methods Ten healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each “home” site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. Results and Discussion Mean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001–0.005 ppm (χ) and 0.0005–0.001 ms−1 (R2*). For χ this is 2.1–4.8 fold better than 3T reports, and 1.1–3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. Conclusion The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T

Getting to know you: Engagement and relationship building: First interim national positive futures case study research report

This report represents the culmination of the first phase of the Positive Futures (PF) Case Studies Research Project rather than a definitive set of findings as such. Rather like the PF programme itself it is very much a work in progress which is evolving all the time in the context of the action research approach we have adopted. This approach involves a cycle of action and reflection, with both the projects and research adapting in relation to the themes that emerge from the study as it progresses. Nevertheless whilst this element of the research has been concerned as much with the establishment of relations with projects and participants as investigating the relationships between them, we have begun to identify a number of tentative themes and findings. These themes are presented in a fashion which is intended to guide the future direction of projects every bit as much as to gain abstract theoretical insight. Yet this recognition of the importance of practicality and direction should not distract from the importance of gaining a wider contextual feel for the programme. For whilst this summary is intended to highlight the key themes emerging from the research and the policy and practice issues associated with them, it is in the detail of the main report that a full appreciation of the PF approach emerges. It is from the more narrative accounts in these subsequent parts that we have drawn the conclusions and recommendations presented here and which will provide the baselines against which we assess future progress. Indeed these accounts are themselves drawn from three regional reports focused on the seven case studies that constitute the overall national research project

Targeting chondroitinase ABC to axons enhances the ability of chondroitinase to promote neurite outgrowth and sprouting.

BACKGROUND:There is currently no effective treatment for promoting regeneration of injured nerves in patients who have sustained injury to the central nervous system such as spinal cord injury. Chondroitinase ABC is an enzyme, which promotes neurite outgrowth and regeneration. It has shown considerable promise as a therapy for these conditions. The aim of the study is to determine if targeting chondroitinase ABC expression to the neuronal axon can further enhance its ability to promote axon outgrowth. Long-distance axon regeneration has not yet been achieved, and would be a significant step in attaining functional recovery following spinal cord injury. METHODOLOGY/PRINCIPAL FINDINGS:To investigate this, neuronal cultures were transfected with constructs encoding axon-targeted chondroitinase, non-targeted chondroitinase or GFP, and the effects on neuron outgrowth and sprouting determined on substrates either permissive or inhibitory to neuron regeneration. The mechanisms underlying the observed effects were also explored. Targeting chondroitinase to the neuronal axon markedly enhances its ability to promote neurite outgrowth. The increase in neurite length is associated with an upregulation of β-integrin staining at the axonal cell surface. Staining for phosphofocal adhesion kinase, is also increased, indicating that the β-integrins are in an activated state. Expression of chondroitinase within the neurons also resulted in a decrease in expression of PTEN and RhoA, molecules which present a block to neurite outgrowth, thus identifying two of the pathways by which ChABC promotes neurite outgrowth. CONCLUSIONS / SIGNIFICANCE:The novel finding that targeting ChABC to the axon significantly enhances its ability to promote neurite extension, suggests that this may be an effective way of promoting long-distance axon regeneration following spinal cord injury. It could also potentially improve its efficacy in the treatment of other pathologies, where it has been shown to promote recovery, such as myocardial infarction, stroke and Parkinson's disease

A comprehensive approach to reablement in dementia

This is the final version of the article. Available from Elsevier via the DOI in this record.© 2017 The Authors As society grapples with an aging population and increasing prevalence of disability, “reablement” as a means of maximizing functional ability in older people is emerging as a potential strategy to help promote independence. Reablement offers an approach to mitigate the impact of dementia on function and independence. This article presents a comprehensive reablement approach across seven domains for the person living with mild-to-moderate dementia. Domains include assessment and medical management, cognitive disability, physical function, acute injury or illness, assistive technology, supportive care, and caregiver support. In the absence of a cure or ability to significantly modify the course of the disease, the message for policy makers, practitioners, families, and persons with dementia needs to be “living well with dementia”, with a focus on maintaining function for as long as possible, regaining lost function when there is the potential to do so, and adapting to lost function that cannot be regained. Service delivery and care of persons with dementia must be reoriented such that evidence-based reablement approaches are integrated into routine care across all sectors.Authors of this article were supported by the International Federation on Ageing and DaneAge to attend the Global Think Tank on Ageing in Copenhagen, Denmark, in late 2015

Trafficking and processing of bacterial proteins by mammalian cells: Insights from chondroitinase ABC.

BACKGROUND: There is very little reported in the literature about the relationship between modifications of bacterial proteins and their secretion by mammalian cells that synthesize them. We previously reported that the secretion of the bacterial enzyme Chondroitinase ABC by mammalian cells requires the strategic removal of at least three N-glycosylation sites. The aim of this study was to determine if it is possible to enhance the efficacy of the enzyme as a treatment for spinal cord injury by increasing the quantity of enzyme secreted or by altering its cellular location. METHODOLOGY/PRINCIPAL FINDINGS: To determine if the efficiency of enzyme secretion could be further increased, cells were transfected with constructs encoding the gene for chondroitinase ABC modified for expression by mammalian cells; these contained additional modifications of strategic N-glycosylation sites or alternative signal sequences to direct secretion of the enzyme from the cells. We show that while removal of certain specific N-glycosylation sites enhances enzyme secretion, N-glycosylation of at least two other sites, N-856 and N-773, is essential for both production and secretion of active enzyme. Furthermore, we find that the signal sequence directing secretion also influences the quantity of enzyme secreted, and that this varies widely amongst the cell types tested. Last, we find that replacing the 3'UTR on the cDNA encoding Chondroitinase ABC with that of β-actin is sufficient to target the enzyme to the neuronal growth cone when transfected into neurons. This also enhances neurite outgrowth on an inhibitory substrate. CONCLUSION/SIGNIFICANCE: Some intracellular trafficking pathways are adversely affected by cryptic signals present in the bacterial gene sequence, whilst unexpectedly others are required for efficient secretion of the enzyme. Furthermore, targeting chondroitinase to the neuronal growth cone promotes its ability to increase neurite outgrowth on an inhibitory substrate. These findings are timely in view of the renewed prospects for gene therapy, and of direct relevance to strategies aimed at expressing foreign proteins in mammalian cells, in particular bacterial proteins