Interpreting the seasonal cycles of atmospheric oxygen and carbon dioxide concentrations at American Samoa Observatory

We present seven years of atmospheric O2/N2 ratio and CO2 concentration data measured from flask samples collected at American Samoa. These data are unusual, exhibiting higher short-term variability, and seasonal cycles not in phase with other sampling stations. The unique nature of atmospheric data from Samoa has been noted previously from measurements of CO2, methyl chloroform, and ozone. With our O2 data, we observe greater magnitude in the short-term variability, but, in contrast, no clear seasonal pattern to this variability. This we attribute to significant regional sources and sinks existing for O2 in both hemispheres, and a dependence on both the latitudinal and altitudinal origins of air masses. We also hypothesize that some samples exhibit a component of "older" air, demonstrating recirculation of air within the tropics. Our findings could be used to help constrain atmospheric transport models which are not well characterized in tropical regions

Doublecortin-expressing cell types in temporal lobe epilepsy

Doublecortin (DCX) is widely regarded as a marker of immature and migrating neurons during development. While DCX expression persists in adults, particularly in the temporal lobe and neurogenic regions, it is unknown how seizures influence its expression. The aim of the present study was to explore the distribution and characteristics of DCX-expressing cells in surgical and postmortem samples from 40 adult and paediatric patients, with epilepsy and with or without hippocampal sclerosis (HS), compared to post mortem controls. The hippocampus (pes and body), parahippocampal gyrus, amygdala, temporal pole and temporal cortex were examined with DCX immunohistochemistry using four commercially-available DCX antibodies, labelled cells were quantified in different regions of interest as well as their co-expression with cell type specific markers (CD68, Iba1, GFAP, GFAP∂, nestin, SOX2, CD34, OLIG2, PDGFRβ, NeuN) and cell cycle marker (MCM2). Histological findings were compared with clinical data, as well as gene expression data obtained from the temporal cortex of 83 temporal lobe epilepsy cases with HS. DCX immunohistochemistry identified immature (Nestin-/NeuN-) neurons in layer II of the temporal neocortex in patients with and without epilepsy. Their number declined significantly with age but was not associated with the presence of hippocampal sclerosis, seizure semiology or memory dysfunction. DCX+ cells were prominent in the paralaminar nuclei and periamygdalar cortex and these declined with age but were not significantly associated with epilepsy history. DCX expressing cells with ramified processes were prominent in all regions, particularly in the hippocampal subgranular zone, where significantly increased numbers were observed in epilepsy samples compared to controls. DCX ramified cells co-expressed Iba1, CD68 and PDGFRβ, and less frequently MCM2, OLIG2 and SOX2, but no co-localization was observed with CD34, nestin or GFAP/GFAP ∂. Gene expression data from neocortical samples in patients with TLE and HS supported ongoing DCX expression in adults. We conclude that DCX identifies a range of morphological cell types in temporal lobe epilepsy, including immature populations, glial and microglial cell types. Their clinical relevance and biological function requires further study but we show some evidence for alteration with age and in epilepsy

EEG correlated functional MRI and postoperative outcome in focal epilepsy

Background: The main challenge in assessing patients with epilepsy for resective surgery is localising seizure onset. Frequently, identification of the irritative and seizure onset zones requires invasive EEG. EEG correlated functional MRI (EEG-fMRI) is a novel imaging technique which may provide localising information with regard to these regions. In patients with focal epilepsy, interictal epileptiform discharge (IED) correlated blood oxygen dependent level (BOLD) signal changes were observed in approximately 50% of patients in whom IEDs are recorded. In 70%, these are concordant with expected seizure onset defined by non-invasive electroclinical information. Assessment of clinical validity requires post-surgical outcome studies which have, to date, been limited to case reports of correlation with intracranial EEG. The value of EEG-fMRI was assessed in patients with focal epilepsy who subsequently underwent epilepsy surgery, and IED correlated fMRI signal changes were related to the resection area and clinical outcome. Methods: Simultaneous EEG-fMRI was recorded in 76 patients undergoing presurgical evaluation and the locations of IED correlated preoperative BOLD signal change were compared with the resected area and postoperative outcome. Results: 21 patients had activations with epileptic activity on EEG-fMRI and 10 underwent surgical resection. Seven of 10 patients were seizure free following surgery and the area of maximal BOLD signal change was concordant with resection in six of seven patients. In the remaining three patients, with reduced seizure frequency post-surgically, areas of significant IED correlated BOLD signal change lay outside the resection. 42 of 55 patients who had no IED related activation underwent resection. Conclusion: These results show the potential value of EEG-fMRI in presurgical evaluation

The spatio-temporal mapping of epileptic networks: Combination of EEG–fMRI and EEG source imaging

Simultaneous EEG–fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG–fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG–fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG–fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks

Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer

BACKGROUND Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance. METHODS Cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines were exposed to various combinations of hypoxia and/or chemotherapeutic drugs as part of a 'hypoxia matrix' designed to cover clinically relevant scenarios in terms of tumour hypoxia. Response to cisplatin was measured by the MTT assay. RNA was extracted from cells treated as part of the hypoxia matrix and interrogated on Affymetrix Human Gene ST 1.0 arrays. Differential gene expression analysis was performed for cells exposed to hypoxia and/or cisplatin. From this, four potential markers of chemoresistance were selected for evaluation in a cohort of ovarian tumour samples by RT-PCR. RESULTS Hypoxia increased resistance to cisplatin in A2780 and A2780cis cells. A plethora of genes were differentially expressed in cells exposed to hypoxia and cisplatin which could be associated with chemoresistance. In ovarian tumour samples, we found trends for upregulation of ANGPTL4 in partial responders and down-regulation in non-responders compared with responders to chemotherapy; down-regulation of HER3 in partial and non-responders compared to responders; and down-regulation of HIF-1α in non-responders compared with responders. CONCLUSION This study has further characterized the relationship between hypoxia and chemoresistance in an ovarian cancer model. We have also identified many potential biomarkers of hypoxia and platinum resistance and provided an initial validation of a subset of these markers in ovarian cancer tissues

The Adoption and Implementation of Evidence-Based Practice (EBP) Among Allied Health Professions.

Background and aims: Evidence-based practice (EBP) is widely accepted within patient care as it ensures health care professionals remain informed of recent evidence and research relating to their clinical practice. However, the particular characteristics detrimental to the successful implementation of EBP within Allied Health Professionals' (AHP) clinical practice are unknown. The purpose of this study was to assess and characterise adoption of EBP within AHP's clinical practice. Methods: Questionnaires comprising the Evidence-Based Practice Questionnaire (EBPQ; Upton and Upton, 2006a) were administered to 154 (response rate=27.3%) newly qualified practitioners (NQPs) from NHSScotland. Data were analysed to determine attitudes, knowledge and skill of EBP; K-means cluster and chi-square analyses were conducted in order to differentiate profiles of NPQs within high-, medium- and low- categories on the EBPQ practice and knowledge/skills sub-sections. Findings: Moderate scores were recorded for NQP's implementation, knowledge, and attitudes toward EBP. Chi-square analysis performed on the high-, moderate- and low- practice and skills' profiles revealed no significant results for NQP's year qualified, age, or year of clinical practice. Conclusions: The findings illustrate that the majority of NQPs have a good understanding of the application and importance of EPB, and suggests the improvement in NQPs training with regards to EBP enables them to successfully transfer acquired knowledge within their clinical practice

The VLT-FLAMES Tarantula Survey X: Evidence for a bimodal distribution of rotational velocities for the single early B-type stars

Aims: Projected rotational velocities (\vsini) have been estimated for 334 targets in the VLT-FLAMES Tarantula survey that do not manifest significant radial velocity variations and are not supergiants. They have spectral types from approximately O9.5 to B3. The estimates have been analysed to infer the underlying rotational velocity distribution, which is critical for understanding the evolution of massive stars. Methods: Projected rotational velocities were deduced from the Fourier transforms of spectral lines, with upper limits also being obtained from profile fitting. For the narrower lined stars, metal and non-diffuse helium lines were adopted, and for the broader lined stars, both non-diffuse and diffuse helium lines; the estimates obtained using the different sets of lines are in good agreement. The uncertainty in the mean estimates is typically 4% for most targets. The iterative deconvolution procedure of Lucy has been used to deduce the probability density distribution of the rotational velocities. Results: Projected rotational velocities range up to approximately 450 \kms and show a bi-modal structure. This is also present in the inferred rotational velocity distribution with 25% of the sample having $0\leq$\ve$\leq$100\,\kms and the high velocity component having \ve$\sim 250$\,\kms. There is no evidence from the spatial and radial velocity distributions of the two components that they represent either field and cluster populations or different episodes of star formation. Be-type stars have also been identified. Conclusions: The bi-modal rotational velocity distribution in our sample resembles that found for late-B and early-A type stars. While magnetic braking appears to be a possible mechanism for producing the low-velocity component, we can not rule out alternative explanations.Comment: to be publisged in A&