Size of hippocampal pyramidal neurons in schizophrenia

Background Meta-analyses of hippocampal size have indicated thatthis structure is smaller in schizophrenia.This could reflect a reductioninthe size of constituent neurons or a reduced number of neurons. Aims To measure the size of hippocampalpyramidalneuronsinthe hippocampalpyramidalneurons inthe brains of peoplewith andwithout schizophrenia. Method Pyramidalneuron size in hippocampal subfieldswas estimated stereologically fromsections taken at 5mmintervals throughoutthewhole length of right and left hippocampi from andleft the brains of13 peoplewith schizophrenia and16 controls.Resultswere assessed using repeated-measures analysis of covariance looking for amain effectof diagnosis and gender, andinteractions of and interactions thesewith side. Results Wewere unable to detect significantdifferences related to diagnosis, gender or side for any hippocampal subfield for this series of cases. Conclusions For this series of brains, hippocampal cell size is unchangedin schizophrenia

When Should we Irradiate the Primary in Metastatic Lung Cancer?

Metastatic lung cancer encompasses a heterogenous group of patients in terms of burdens of disease, ranging from patients with extensive metastases to those with a limited number of metastatic lesions (oligometastatic disease). Histopathological heterogeneity also exists within two broad categories, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), portraying different patterns and evolution of disease. Local consolidative therapy to the primary tumour and metastatic sites, including surgery and/or radical dose radiotherapy, is increasingly being used to improve survival outcomes, particularly in the context of oligometastatic disease, with or without the use of molecular targeted therapy and immunotherapy. Recently, randomised studies in oligometastatic NSCLC have shown that local consolidative therapy may confer a survival advantage. This review explores whether treating just the primary tumour with radiotherapy may similarly produce improved clinical outcomes. Such a treatment strategy may carry less potential toxicity than treating multiple sites upfront. The biological rationale behind the potential benefits of treating just the primary in metastatic malignancy is discussed. The clinical evidence of such an approach across tumour sites, such as breast and prostate cancer, is also explored. Then the review focuses on treating the primary in NSCLC and SCLC with radiotherapy, by first exploring patterns of failure in metastatic NSCLC and second exploring evidence on survival outcomes from studies in metastatic NSCLC and SCLC. It is challenging to draw conclusions on the clinical benefit of treating the primary cancer in isolation from the evidence available. This highlights the need to collect data within the ongoing clinical trials on the clinical outcome and toxicity of radiotherapy delivery to primary thoracic disease specifically. This challenge also identifies the need to design future clinical trials to produce randomised evidence for such an approach

Measuring Political Brand Equity in Ireland

Measuring Political Brand Equity in the Republic of Ireland This paper will apply cognitive mapping techniques to understand the manner in which political brand equity is formed and distributed amongst the four largest Irish political parties from the perspective of citizens. It assesses the fundamental aspects of branding and brand equity in the marketing and political marketing literatures and offers and overview of the market in question – the Irish political environment. Primary data was generated through the participation of 232 citizens in the political brand elicitation stage and a further 75 citizens were involved in the construction of the cognitive maps of brand equity. From the mapping process we see that Irish political parties brands are plagued by a number of negative associations. Fianna Fáil’s brand is overshadowed by past mistakes and past leaders with bad reputations; whilst the Fine Gael brand is wracked by low levels of engagement. This paper constitutes the first attempt to measure the political brand equity of Irish political parties

Biodegradation of the Alkaline Cellulose Degradation Products Generated during Radioactive Waste Disposal.

The anoxic, alkaline hydrolysis of cellulosic materials generates a range of cellulose degradation products (CDP) including α and β forms of isosaccharinic acid (ISA) and is expected to occur in radioactive waste disposal sites receiving intermediate level radioactive wastes. The generation of ISA's is of particular relevance to the disposal of these wastes since they are able to form complexes with radioelements such as Pu enhancing their migration. This study demonstrates that microbial communities present in near-surface anoxic sediments are able to degrade CDP including both forms of ISA via iron reduction, sulphate reduction and methanogenesis, without any prior exposure to these substrates. No significant difference (n = 6, p = 0.118) in α and β ISA degradation rates were seen under either iron reducing, sulphate reducing or methanogenic conditions, giving an overall mean degradation rate of 4.7×10−2 hr−1 (SE±2.9×10−3). These results suggest that a radioactive waste disposal site is likely to be colonised by organisms able to degrade CDP and associated ISA's during the construction and operational phase of the facility

The Electrodeposition of the Magnetic Shape Memory Alloy Ni-Mn-Ga

Shape memory alloy (SMA): Material capable of overcoming large strains to return to a pre-deformed shape via a thermally induced martensitic phase transformation. In magnetic SMA, the shape change can be induced with a magnetic field

Drugs-related death soon after hospital discharge among drug treatment clients in Scotland:record linkage, validation and investigation of risk factors.

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting

Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial : FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Fullthickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2–3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity ≤ 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence on the role of ILM peeling in FTMH surgery. Trial registration: This trial is registered with Current Controlled Trials ISRCTN number 33175422 and Clinical Trials.gov identifier NCT00286507.Chief Scientist Office, Scotland (project ref no CZH/4/235), NHS GrampianPeer reviewedPublisher PD

CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

Monotonicity of Fitness Landscapes and Mutation Rate Control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms