Chronic thoracic hemisection spinal cord injury in adult rats induces a progressive decline in transmission from uninjured fibers to lumbar motoneurons

Although most spinal cord injuries are anatomically incomplete, only limited functional recovery has been observed in people and rats with partial lesions. To address why surviving fibers cannot mediate more complete recovery, we evaluated the physiological and anatomical status of spared fibers after unilateral hemisection (HX) of thoracic spinal cord in adult rats. We made intracellular and extracellular recordings at L5 (below HX) in response to electrical stimulation of contralateral white matter above (T6) and below (L1) HX. Responses from T6 displayed reduced amplitude, increased latency and elevated stimulus threshold in the fibers across from HX, beginning 1-2 weeks after HX. Ultrastructural analysis revealed demyelination of intact axons contralateral to the HX, with a time course similar to the conduction changes. Behavioral studies indicated partial recovery which arrested when conduction deficits began. These findings suggest a chronic pathological state in intact fibers and necessity for prompt treatment to minimize it

Increased antigen specific T cell numbers in the absence of altered migration or division rates as a result of mucosal cholera toxin administration

Cholera toxin (CT) is a mucosal adjuvant capable of inducing strong immune responses to co-administered antigens following oral or intranasal immunization of mice. To date, the direct effect of CT on antigen-specific CD4(+) T cell migration and proliferation profiles in vivo is not well characterized. In this study, the effect of CT on the migration pattern and proliferative responses of adoptively transferred, CD4(+) TCR transgenic T cells in orally or intranasally vaccinated mice, was analyzed by flow cytometry. GFP-expressing or CFSE-labeled OT-II lymphocytes were adoptively transferred to naïve C57BL/6 mice, and mice were subsequently vaccinated with OVA with or without CT via the oral or intranasal route. CT did not alter the migration pattern of antigen-specific T cells, regardless of the route of immunization, but increased the number of transgenic CD4(+) T cells in draining lymphoid tissue. This increase in the number of transgenic CD4(+) T cells was not due to cells undergoing more rounds of cellular division in vivo, suggesting that CT may exert an indirect adjuvant effect on CD4(+) T cells. The findings reported here suggest that CT functions as a mucosal adjuvant by increasing the number of antigen specific CD4(+) T cells independent of their migration pattern or kinetics of cellular division.Grant support was received from the National Health and Medical Research Council of Australia (NHMRC). OLW is a recipient of an R.D. Wright Career Development Award

NCAM: a surface marker for human small cell lung cancer cells

Immunocytochemical and immunochemical techniques were used to study the expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopic levels on small cell lung cancer cells. The NCAM polypeptide of Mr 140000 (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer cell lines: it was not detected in cell lines obtained from one patient with a mesothelioma, in two cases of adenocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by immunoblotting in all the lung cancer cell lines tested and synaptophysin in all but the adenocarcinoma cell lines. These antigens were localized intracellularly. The specific expression of NCAM 140 by human small and large cell lung carcinomas suggests its potential as a diagnostic marker

Plasma plume effects on the conductivity of amorphous-LaAlO₃/SrTiO₃ interfaces grown by pulsed laser deposition in O₂ and Ar

Amorphous LaAlO3/SrTiO3 interfaces exhibit metallic conductivity similarto those found for the extensively studied crystalline-LaAlO3/SrTiO3 interfaces. Here, we investigate the conductivity of the amorphous-LaAlO3/SrTiO3 interfaces grown in different pressures of O2 and Ar background gases. During the deposition, the LaAlO3 ablation plume is also studied, in situ, by fast photography and space-resolved optical emission spectroscopy. An interesting correlation between interfacial conductivity and kinetic energy of the Al atoms in the plume is observed: to assure conducting interfaces of amorphous-LaAlO3/SrTiO3, the kinetic energy of Al should be higher than 1 eV. Our findings add further insights on mechanisms leading to interfacial conductivity in SrTiO3-based oxide heterostructures

An agenda for future research regarding the mental health of young people with care experience

Young people who are currently or were previously in state care have consistently been found to have much higher rates of mental health and neurodevelopmental difficulties than the general youth population. While a number of high-quality reviews highlight what research has been undertaken in relation to the mental health of young people with care experience and the gaps in our knowledge and understanding, there is, until now, no consensus, so far as we aware, as to where our collective research efforts should be directed with this important group. Through a series of UK wide workshops, we undertook a consultative process to identify an agreed research agenda between those with lived experience of being in care (n = 15), practitioners, policy makers and researchers (n = 59), for future research regarding the mental health of young people with care experience, including those who are neurodiverse/have a neurodevelopmental difficulty. This consensus statement identified 21 foci within four broad categories: how we conceptualize mental health; under-studied populations; under-studied topics; and underused methodologies. We hope that those who commission, fund and undertake research will engage in this discussion about the future agenda for research regarding the mental health of young people with care experience

Pathways to professionalism? Quality improvement, care pathways, and the interplay of standardisation and clinical autonomy.

Care pathways are a prominent feature of efforts to improve healthcare quality, outcomes and accountability, but sociological studies of pathways often find professional resistance to standardisation. This qualitative study examined the adoption and adaptation of a novel pathway as part of a randomised controlled trial in an unusually complex, non-linear field - emergency general surgery - by teams of surgeons and physicians in six theoretically sampled sites in the UK. We find near-universal receptivity to the concept of a pathway as a means of improving peri-operative processes and outcomes, but concern about the impact on appropriate professional judgement. However, this concern translated not into resistance and implementation failure, but into a nuancing of the pathways-as-realised in each site, and their use as a means of enhancing professional decision-making and inter-professional collaboration. We discuss our findings in the context of recent literature on the interplay between managerialism and professionalism in healthcare, and highlight practical and theoretical implications

Autologous Stem Cell Transplant is Feasible in Very Elderly Patients with Lymphoma and Limited Comorbidity

In patients with recurrent Hodgkin or non-Hodgkin\u27s lymphoma, autologous stem cell transplantation (ASCT) can offer potential for cure or long-term remission. Because of potential toxicity, elderly patients are usually not considered candidates, but data regarding tolerability and efficacy in this group are lacking. The transplant database at Weill Cornell Medical College was reviewed to identify patients with lymphoma undergoing ASCT at age 69 or greater. Clinical data and comorbidities were correlated with outcome. Twenty-one patients were identified. Sixteen of 19 evaluable patients (76%) achieved complete remission following ASCT, while 2 patients died before response assessment. Median progression-free survival following ASCT was 8 months and median overall survival was 18 months. Age was not predictive of overall survival, but patients 75 and older had inferior progression-free survival compared to younger patients. High-risk status by hematopoietic stem cell transplant comorbidity index (HCT-CI) was associated with short overall survival and high transplant-related mortality. ASCT is feasible and of potential benefit in selected elderly lymphoma patients. Consideration of comorbidities, rather than age alone, may allow selection of patients likely to tolerate and benefit from ASCT

Autologous Stem Cell Transplant is Feasible in Very Elderly Patients with Lymphoma and Limited Comorbidity

In patients with recurrent Hodgkin or non-Hodgkin\u27s lymphoma, autologous stem cell transplantation (ASCT) can offer potential for cure or long-term remission. Because of potential toxicity, elderly patients are usually not considered candidates, but data regarding tolerability and efficacy in this group are lacking. The transplant database at Weill Cornell Medical College was reviewed to identify patients with lymphoma undergoing ASCT at age 69 or greater. Clinical data and comorbidities were correlated with outcome. Twenty-one patients were identified. Sixteen of 19 evaluable patients (76%) achieved complete remission following ASCT, while 2 patients died before response assessment. Median progression-free survival following ASCT was 8 months and median overall survival was 18 months. Age was not predictive of overall survival, but patients 75 and older had inferior progression-free survival compared to younger patients. High-risk status by hematopoietic stem cell transplant comorbidity index (HCT-CI) was associated with short overall survival and high transplant-related mortality. ASCT is feasible and of potential benefit in selected elderly lymphoma patients. Consideration of comorbidities, rather than age alone, may allow selection of patients likely to tolerate and benefit from ASCT

Multi-decadal environmental change in the Barents Sea recorded by seal teeth

This work resulted from the ARISE project (NE/P006035/1, NE/P006000/1), part of the Changing Arctic Ocean programme, jointly funded by the UKRI Natural Environment Research Council (NERC). We thank Jim Ball for his help in the isotopic lab in Liverpool University. This work resulted from the ARISE project, part of the Changing Arctic Ocean programme.Multiple environmental forcings, such as warming and changes in ocean circulation and nutrient supply, are affecting the base of Arctic marine ecosystems, with cascading effects on the entire food web through bottom-up control. Stable nitrogen isotopes (δ15N) can be used to detect and unravel the impact of these forcings on this unique ecosystem, if the many processes that affect the δ15N values are constrained. Combining unique 60-year records from compound specific δ15N biomarkers on harp seal teeth alongside state-of-the-art ocean modelling, we observed a significant decline in the δ15N values at the base of the Barents Sea food web from 1951 to 2012. This strong and persistent decadal trend emerges due to the combination of anthropogenic atmospheric nitrogen deposition in the Atlantic, increased northward transport of Atlantic water through Arctic gateways and local feedbacks from increasing Arctic primary production. Our results suggest that the Arctic ecosystem has been responding to anthropogenically induced local and remote drivers, linked to changing ocean biology, chemistry and physics, for at least 60 years. Accounting for these trends in δ15N values at the base of the food web is essential to accurately detect ecosystem restructuring in this rapidly changing environment.Publisher PDFPeer reviewe

Critical influence of target-to-substrate distance on conductive properties of LaGaO3/SrTiO3 interfaces deposited at 10-1 mbar oxygen pressure

We investigate pulsed laser deposition of LaGaO3/SrTiO3 at 10-1 mbar oxygen background pressure, demonstrating the critical effect of the target-to-substrate distance, dTS, on the interface sheet resistance, Rs. The interface turns from insulating to metallic by progressively decreasing dTS. The analysis of the LaGaO3 plume evidences the important role of the plume propagation dynamics on the interface properties. These results demonstrate the growth of conducting interfaces at an oxygen pressure of 10-1 mbar, an experimental condition where a well-oxygenated heterostructures with a reduced content of oxygen defects is expected.Comment: 16 pages, 3 figure