1,943 research outputs found

    SURVIVING POVERTY: Stress and Coping in the Lives of Housed and Homeless Mothers

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73602/1/h0080357.pd

    Anatomical and molecular properties of long descending propriospinal neurons in mice

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    Long descending propriospinal neurons (LDPNs) are interneurons that form direct connections between cervical and lumbar spinal circuits. LDPNs are involved in interlimb coordination and are important mediators of functional recovery after spinal cord injury (SCI). Much of what we know about LDPNs comes from a range of species, however, the increased use of transgenic mouse lines to better define neuronal populations calls for a more complete characterisation of LDPNs in mice. In this study, we examined the cell body location, inhibitory neurotransmitter phenotype, developmental provenance, morphology and synaptic inputs of mouse LDPNs throughout the cervical and upper thoracic spinal cord. LDPNs were retrogradely labelled from the lumbar spinal cord to map cell body locations throughout the cervical and upper thoracic segments. Ipsilateral LDPNs were distributed throughout the dorsal, intermediate and ventral grey matter as well as the lateral spinal nucleus and lateral cervical nucleus. In contrast, contralateral LDPNs were more densely concentrated in the ventromedial grey matter. Retrograde labelling in GlyT2GFP and GAD67GFP mice showed the majority of inhibitory LDPNs project either ipsilaterally or adjacent to the midline. Additionally, we used several transgenic mouse lines to define the developmental provenance of LDPNs and found that V2b positive neurons form a subset of ipsilaterally projecting LDPNs. Finally, a population of Neurobiotin (NB) labelled LDPNs were assessed in detail to examine morphology and plot the spatial distribution of contacts from a variety of neurochemically distinct axon terminals. These results provide important baseline data in mice for future work on their role in locomotion and recovery from SCI

    Blue carbon benefits from global saltmarsh restoration

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    Coastal saltmarshes are found globally, yet are 25%–50% reduced compared with their historical cover. Restoration is incentivised by the promise that marshes are efficient storers of ‘blue’ carbon, although the claim lacks substantiation across global contexts. We synthesised data from 431 studies to quantify the benefits of saltmarsh restoration to carbon accumulation and greenhouse gas uptake. The results showed global marshes store approximately 1.41–2.44 Pg carbon. Restored marshes had very low greenhouse gas (GHG) fluxes and rapid carbon accumulation, resulting in a mean net accumulation rate of 64.70 t CO2e ha−1 year−1. Using this estimate and potential restoration rates, we find saltmarsh regeneration could result in 12.93–207.03 Mt CO2e accumulation per year, offsetting the equivalent of up to 0.51% global energy-related CO2 emissions—a substantial amount, considering marshes represent <1% of Earth's surface. Carbon accumulation rates and GHG fluxes varied contextually with temperature, rainfall and dominant vegetation, with the eastern coasts of the USA and Australia particular hotspots for carbon storage. While the study reveals paucity of data for some variables and continents, suggesting need for further research, the potential for saltmarsh restoration to offset carbon emissions is clear. The ability to facilitate natural carbon accumulation by saltmarshes now rests principally on the action of the management-policy community and on financial opportunities for supporting restoration

    Evidence for holistic processing of faces viewed as photographic negatives

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    Inversion and photographic negation both impair face recognition. Inversion seems to disrupt processing of the spatial relationship between facial features ('relational' processing) which normally occurs with upright faces and which facilitates their recognition. It remains unclear why negation affects recognition. To find out if negation impairs relational processing, we investigated whether negative faces are subject to the 'chimeric-face effect'. Recognition of the top half of a composite face (constructed from top and bottom halves of different faces) is difficult when the face is upright, but not when it is inverted. To perform this task successfully, the bottom half of the face has to be disregarded, but the relational processing which normally occurs with upright faces makes this difficult. Inversion reduces relational processing and thus facilitates performance on this particular task. In our experiments, subjects saw pairs of chimeric faces and had to decide whether or not the top halves were identical. On half the trials the two chimeras had identical tops; on the remaining trials the top halves were different. (The bottom halves were always different.) All permutations of orientation (upright or inverted) and luminance (normal or negative) were used. In experiment 1, each pair of 'identical' top halves were the same in all respects. Experiment 2 used differently oriented views of the same person, to preclude matches being based on incidental features of the images rather than the faces displayed within them. In both experiments, similar chimeric-face effects were obtained with both positive and negative faces, implying that negative faces evoke some form of relational processing. It is argued that there may be more than one kind of relational processing involved in face recognition: the 'chimeric-face effect' may reflect an initial 'holistic' processing which binds facial features into a 'Gestalt', rather than being a demonstration of the configurational processing involved in individual recognition

    Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel

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    &lt;b&gt;Background&lt;/b&gt; Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0–300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p &lt; .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.&lt;p&gt;&lt;/p&gt

    Investigating the effectiveness of the Mediterranean diet in pregnant women for the primary prevention of asthma and allergy in high-risk infants: protocol for a pilot randomised controlled trial

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    This research is funded by the Chief Scientist Office of The Scottish Government/Chief Medical Officer Directorate (Grant CZG/2/558). The authors would like to acknowledge the staff involved in the NHS ethical and research and development review processes, and staff at the Health Records Department of the Edinburgh Royal Infirmary for their help in getting the recruitment material to potential participants. The staff at the ultrasound/X-ray clinics at the two NHS Lothian sites where the participants are met by the researcher are most helpful and accommodating. The authors thank Anne Galloway (dietitian) who, when available, is delivering the intervention at one of the sites. They would also like to thank the participants for volunteering to take part, Dr Rob Elton the independent statistician, and Julia Clark (dietitian), Dr Ulugbek Nurmatov (researcher), and our Consumer Involvement Group for their input.Peer reviewedPublisher PD

    Igf2 pathway dependency of the Trp53 developmental and tumour phenotypes

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    Insulin-like growth factor 2 (IGF2) and the transformation related protein 53 (Trp53) are potent regulators of cell growth and metabolism in development and cancer. In vitro evidence suggests several mechanistic pathway interactions. Here, we tested whether loss of function of p53 leads to IGF2 ligand pathway dependency in vivo. Developmental lethality occurred in p53 homozygote null mice that lacked the paternal expressed allele of imprinted Igf2. Further lethality due to post-natal lung haemorrhage occurred in female progeny with Igf2 paternal null allele only if derived from double heterozygote null fathers, and was associated with a specific gene expression signature. Conditional deletion of Igf2(fl/fl) attenuated the rapid tumour onset promoted by homozygous deletion of p53(fl/fl) . Accelerated carcinoma and sarcoma tumour formation in p53(+/-) females with bi-allelic Igf2 expression was associated with reductions in p53 loss of heterozygosity and apoptosis. Igf2 genetic dependency of the p53 null phenotype during development and tumour formation suggests that targeting the IGF2 pathway may be useful in the prevention and treatment of human tumours with a disrupted Trp53 pathway.</p

    Making the diagnosis of Chronic Fatigue Syndrome/Myalgic Encephalitis in primary care: a qualitative study

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    <p>Abstract</p> <p>Background</p> <p>NICE guidelines emphasise the role of the primary care team in the management of patients with Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME). A key stage in effective management is making an accurate early diagnosis, supported by appropriate referral.</p> <p>Methods</p> <p>A nested qualitative study within a multi-centre randomised controlled trial which aimed to explore GPs' views on their role in making the diagnosis of CFS/ME and subsequent management of patients in primary care. Semi-structured interviews with 22 GPs. Interviews were transcribed verbatim and an iterative approach used to develop themes from the dataset.</p> <p>Results</p> <p>GPs described difficulties in defining CFS/ME and suggested that their role in making a diagnosis was to exclude physical causes for the patient's symptoms, but they reported little confidence in positively attributing the label of CFS/ME to a patient and their symptoms. GPs suggested that the label of CFS/ME could be potentially harmful for the patient. The role of referral to secondary care was debated and GPs struggled defining their own role in management of this group of patients.</p> <p>Conclusions</p> <p>Until GPs feel comfortable making the diagnosis of CFS/ME and facilitating initial management, and have appropriate services to refer patients to, there will continue to be delays in confirming the diagnosis and patients presenting in primary care with fatigue may not receive appropriate care.</p> <p>Trial Registration</p> <p>ISRCTN 74156610</p

    The cellular and synaptic architecture of the mechanosensory dorsal horn

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    The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception
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