Role of the Calcium Plateau in the Neuronal Injury and Behavioral Morbidities Following Organophosphate Intoxication

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular calcium-induced calcium release such as dantrolene, levetiracetam, and carisbamate lowered OP-SE mediated protracted calcium elevations. Given the critical role of calcium signaling in modulating behavior and cell-death mechanisms, drugs targeted at preventing the development of the calcium plateau could enhance neuroprotection, help reduce morbidity and improve outcome following survival of OP SE

Disarming not defending Africa

Most sub-Saharan states cannot protect themselves from major military threats, especially extra-continental ones. From the perspective of the big international players the question is: should Africa be protected? In this collection of essays, the impact of Africa's global marginalisation is duly noted. This fundamental facet of Africa's security dilemma, however, is not analysed in any meaningful way. True, the usual malaises, including 'ethnic nationalism', are paraded, but there is no mention of the current debate on how Africa's 'ethnic' wars are interpreted by the international media, and its assumed impact on humanitarian and military intervention. If they have not done so already, the editors should read Tim Allen and Jean Seaton's new book, The Media of Conflict. Here the implications of the so-called second scramble for Africa, including the role of aid agencies and the International Monetary Fund, are scrutinised. Seaton and Allen reject the notion of mindless, primordial violence in Africa, and instead examine the repercussions of foreign intervention (most egregiously French meddling in Rwanda) as well as the rational economic motivations of the assorted warlords.</p

Regenerative medicine: Stroke survivor and carer views and motivations towards a proposed stem cell clinical trial using placebo neurosurgery

Background  Few studies explore stroke survivor views and motivations towards stem cell therapy (SCT). This qualitative study explores the views and motivations of both stroke survivors and their partners/carers towards a proposed 2-arm Phase III Randomised Controlled Trial (RCT) comparing intracerebral insertion of stem cells with placebo neurosurgery in stroke survivors with disability.  Objective  To explore views and motivations towards a proposed 2-arm stem cell trial and identify factors that may impede and enhance participation.  Design  This study adopts a naturalistic design to explore the complexity of this field, employing a participatory action-research approach comprising a specialized Conversation (World) Café form of focus group. Data were collected via 5 Conversation Cafés with stroke survivors (age 40-75) and partners/carers between June and October 2016. Of 66 participants, 53 (31 male, 22 female) were stroke survivors and 13 (6 female, 7 male) were partners/carers. Qualitative data were analysed using a thematic approach.  Discussion and Conclusion  Stroke survivor views and motivations reflect anticipation of the personal and future benefits of regenerative medicine. Partners/carers sought to balance the value of stroke survivor hope with carrying the weight of hope as carer, a conflict burden adding to known caregiver burden. All participants expressed the need for during and post-trial psychological support. This study provides a rare opportunity to explore the prospective views and motivations of stroke survivors and their partners/carers towards a proposed Phase III 2-arm RCT. This adds weight to qualitative evidence exploring capacity, consent, decision making, perceptions of treatment risk and supports required for clinical trial participation

Patient-initiated recruitment for clinical research: Evaluation of an outpatient letter research statement

Background: UK Hospital Trusts are charged with increasing patients’ research awareness and willingness to take part in research. This includes implementing strategies to encourage patient-initiated enquiries about participation. Objectives: To evaluate the impact of a research statement inserted in outpatient letters in one clinical service, and to derive suggestions on potential steps towards increasing patient-initiated recruitment. Setting: A medical outpatient clinic of a research-active hospital trust, serving an inner-city multi-ethnic population across two boroughs. Methods: Pre-intervention and post-intervention questionnaires were administered face-to-face to new patients. Questionnaires included closed questions and one open comments section. Data were analysed for frequencies, with thematic coding of open-ended responses. Results: The response rates were 87% for the pre-intervention survey and 92% for the post-intervention survey. In the post-intervention survey, 85% of patients did not notice the research statement in the letter. More than half found the statement “a little unclear,” whilst one-third considered it “clear.” Three-quarters of respondents perceived the statement to be “a little helpful.” Only one person enquired about participating in clinical research having read the statement in the outpatient letter. Conclusion: The analysis suggests that simple, single-solution approaches such as including research statements in outpatient letters are unlikely to be sufficient to significantly facilitate patient-initiated recruitment. Recruitment efforts need to take into consideration the diversity of patient constituencies including the reasons they seek health care, and how patients can meaningfully access information (research literacy)

Does cancer research focus on areas of importance to patients?

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The majority of research ideas are proposed by clinicians or scientists and little is currently known about which areas of research patients feel are important. We performed a 4 week pilot patient survey at the Royal Marsden (a specialist cancer centre) to investigate patients' views on priorities for cancer research. A total of 780 patients completed the survey and the top research priorities were identified as: detection and prevention of cancer, scientific understanding, curative treatment and personalised treatment. The top research priorities were remarkably consistent across age, gender and a variety of tumour types. We believe that patients' views should be considered alongside those of clinicians and researchers when devising research proposals and strategies.Peer reviewedFinal Published versio

Case Report: Response to ipilimumab and nivolumab in a patient with adrenocortical carcinoma

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with limited treatment options. The evidence for the use of immunotherapy in ACC has been conflicting, with overall response rates ranging from 6 – 33%. Case presentation: We describe the case of a 32 year old patient who was initially thought to have an inoperable clear cell renal cell carcinoma and was treated with immunotherapy with ipilimumab and nivolumab. The patient had an excellent partial response to treatment. Further work-up prior to consideration of surgery demonstrated that the tumour was an ACC, rather than a renal cancer. She had a right adrenalectomy and right hepatectomy, achieving an R0 resection and remains disease-free one year after surgery. Conclusion: This case illustrates the challenge of diagnosing ACC, and that doublet immunotherapy with ipilimumab and nivolumab can have significant clinical efficacy in ACC

Synthesis and properties of [Pt(4-CO₂CH₃-py)₂(mnt)]: Comparison of pyridyl and bipyridyl-based dyes for solar cells

In the present paper, we consider a position vector of an arbitrary curve in the three-dimensional Galilean space G3. Furthermore, we give some conditions on the curvatures of this arbitrary curve to study special curves and their Smarandache curves. Finally, in the light of this study, some related examples of these curves are provided and plotted

FOLFIRINOX and radiotherapy for locally advanced pancreatic cancer: A cohort study

Introduction: One-third of the patients with pancreatic cancer present with locally advanced unresectable pancreatic cancer (LAPC). Our aim was to determine survival outcomes and toxicity after FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) followed by radiotherapy (RT) in biopsy-proven patients with LAPC. Methods: We analysed a cohort of biopsy-proven patients with LAPC, who were eligible for induction FOLFIRINOX (eight cycles) and subsequent RT (30 fractions, 60 Gy). Eligible patients underwent a staging laparoscopy to detect occult metastasis before the treatment. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), treatment-related toxicity, and resection rate. Results: Forty-four patients were diagnosed with biopsy-proven LAPC. Twenty-five patients were eligible and all underwent staging laparoscopy before the treatment. In three (12%) patients occult metastases were found. Twenty-two patients started induction FOLFIRINOX, 17 (77%) completed all cycles. Seventeen (77%) patients were treated with subsequent RT, with 16 (94%) receiving the full dosage. Three (14%) patients underwent a radical resection after the treatment. Median OS was 15.4 months (95% confidence interval [CI], 10.0-20.7), median PFS was 11 months (95% CI, 7.7-14.4). Conclusions: Median OS after FOLFIRINOX and RT was 15 months in patients with LAPC. Toxicity remains severe, however, mo