An exploration of the effectiveness of artificial mini-magnetospheres as a potential solar storm shelter for long term human space missions

If mankind is to explore the solar system beyond the confines of our Earth and Moon the problem of radiation protection must be addressed. Galactic cosmic rays and highly variable energetic solar particles are an ever-present hazard in interplanetary space. Electric and/or magnetic fields have been suggested as deflection shields in the past, but these treated space as an empty vacuum. In fact it is not empty. Space contains a plasma known as the solar wind; a constant flow of protons and electrons coming from the Sun. In this paper we explore the effectiveness of a “mini-magnetosphere” acting as a radiation protection shield. We explicitly include the plasma physics necessary to account for the solar wind and its induced effects. We show that, by capturing/containing this plasma, we enhance the effectiveness of the shield. Further evidence to support our conclusions can be obtained from studying naturally occurring “mini-magnetospheres” on the Moon. These magnetic anomalies (related to “lunar swirls”) exhibit many of the effects seen in laboratory experiments and computer simulations. If shown to be feasible, this technology could become the gateway to manned exploration of interplanetary space

Development of assessment toolkits for improving the diagnosis of the Lewy body dementias: feasibility study within the DIAMOND Lewy study.

$\textbf{Objective:}$ The Lewy body dementias (LBD, dementia with Lewy bodies and Parkinson's disease dementia) are the second most common cause of neurodegenerative dementia but remain under-recognised, with long delays from initial assessment to diagnosis. Whilst validated instruments have been developed for key symptoms, there is no brief instrument for overall diagnostic assessment suitable for routine practice. We here report the development of such assessment toolkits. $\textbf{Methods:}$ We developed the LBD assessment toolkits in three stages. First, we conducted a systematic search for brief validated assessments for key symptoms and combined these into draft instruments. Second, we obtained feedback on acceptability and feasibility through two rounds of interviews with our patient and public involvement group. This led to modification of the toolkits. Finally, we piloted the toolkits in a feasibility study in routine dementia and Parkinson's disease services to produce final instruments suitable for routine clinical practice. $\textbf{Results:}$ Eleven clinicians, working in both dementia/memory assessment and Parkinson's disease/movement disorder services, consented to pilot the assessment toolkits and provide feedback on their feasibility. Clinicians worked in routine health service (not academic) settings and piloted the draft toolkits by integrating them into their regular clinical assessments. Feedback obtained informally, by written comments and through qualitative interviews led to modifications and production of final acceptable versions. $\textbf{Conclusions:}$ We were able to address an important need, the under-diagnosis of LBD, by developing toolkits for improving the recognition and diagnosis of the LBD, which were acceptable to clinicians working in routine dementia and Parkinson's disease services.This study was supported by the NIHR under its Programme Grants for Applied Research programme (DTC-RP-PG-0311-12001); the NIHR Biomedical Research Unit in Lewy Body Dementia and Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University; and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Development of assessment toolkits for improving the diagnosis of the Lewy body dementias: feasibility study within the DIAMOND Lewy study.

OBJECTIVE: The Lewy body dementias (LBD, dementia with Lewy bodies and Parkinson's disease dementia) are the second most common cause of neurodegenerative dementia but remain under-recognised, with long delays from initial assessment to diagnosis. Whilst validated instruments have been developed for key symptoms, there is no brief instrument for overall diagnostic assessment suitable for routine practice. We here report the development of such assessment toolkits. METHODS: We developed the LBD assessment toolkits in three stages. First, we conducted a systematic search for brief validated assessments for key symptoms and combined these into draft instruments. Second, we obtained feedback on acceptability and feasibility through two rounds of interviews with our patient and public involvement group. This led to modification of the toolkits. Finally, we piloted the toolkits in a feasibility study in routine dementia and Parkinson's disease services to produce final instruments suitable for routine clinical practice. RESULTS: Eleven clinicians, working in both dementia/memory assessment and Parkinson's disease/movement disorder services, consented to pilot the assessment toolkits and provide feedback on their feasibility. Clinicians worked in routine health service (not academic) settings and piloted the draft toolkits by integrating them into their regular clinical assessments. Feedback obtained informally, by written comments and through qualitative interviews led to modifications and production of final acceptable versions. CONCLUSIONS: We were able to address an important need, the under-diagnosis of LBD, by developing toolkits for improving the recognition and diagnosis of the LBD, which were acceptable to clinicians working in routine dementia and Parkinson's disease services. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons, Ltd.This study was supported by the NIHR under its Programme Grants for Applied Research programme (DTC-RP-PG-0311-12001); the NIHR Biomedical Research Unit in Lewy Body Dementia and Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University; and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Collagen-Like Proteins in Pathogenic E. coli Strains

The genome sequences of enterohaemorrhagic E. coli O157:H7 strains show multiple open-reading frames with collagen-like sequences that are absent from the common laboratory strain K-12. These putative collagens are included in prophages embedded in O157:H7 genomes. These prophages carry numerous genes related to strain virulence and have been shown to be inducible and capable of disseminating virulence factors by horizontal gene transfer. We have cloned two collagen-like proteins from E. coli O157:H7 into a laboratory strain and analysed the structure and conformation of the recombinant proteins and several of their constituting domains by a variety of spectroscopic, biophysical, and electron microscopy techniques. We show that these molecules exhibit many of the characteristics of vertebrate collagens, including trimer formation and the presence of a collagen triple helical domain. They also contain a C-terminal trimerization domain, and a trimeric α-helical coiled-coil domain with an unusual amino acid sequence almost completely lacking leucine, valine or isoleucine residues. Intriguingly, these molecules show high thermal stability, with the collagen domain being more stable than those of vertebrate fibrillar collagens, which are much longer and post-translationally modified. Under the electron microscope, collagen-like proteins from E. coli O157:H7 show a dumbbell shape, with two globular domains joined by a hinged stalk. This morphology is consistent with their likely role as trimeric phage side-tail proteins that participate in the attachment of phage particles to E. coli target cells, either directly or through assembly with other phage tail proteins. Thus, collagen-like proteins in enterohaemorrhagic E. coli genomes may have a direct role in the dissemination of virulence-related genes through infection of harmless strains by induced bacteriophages

The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms. Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011. Results: We recruited 64 HIV-infected and 107 HIV-uninfected patients. Those with HIV were significantly younger (P < .001) and less likely to have established vascular risk factors. Patients with HIV were more likely to have large artery disease (21% vs 10%; P < .001). The commonest etiology was HIV-associated vasculopathy (24 [38%]), followed by opportunistic infections (16 [25%]). Sixteen of 64 (25%) had a stroke soon after starting antiretroviral therapy (ART), suggesting an immune reconstitution-like syndrome. In this group, CD4+ T-lymphocyte count was low, despite a significantly lower HIV viral load in those recently started on treatment (P < .001). Conclusions: HIV-associated vasculopathy and opportunistic infections are common causes of HIV-related ischemic stroke. Furthermore, subtypes of HIV-associated vasculopathy may manifest as a result of an immune reconstitution-like syndrome after starting ART. A better understanding of this mechanism may point toward new treatments

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Accuracy of Electronic Health Record Data for Identifying Stroke Cases in Large-Scale Epidemiological Studies: A Systematic Review from the UK Biobank Stroke Outcomes Group

Long-term follow-up of population-based prospective studies is often achieved through linkages to coded regional or national health care data. Our knowledge of the accuracy of such data is incomplete. To inform methods for identifying stroke cases in UK Biobank (a prospective study of 503,000 UK adults recruited in middle-age), we systematically evaluated the accuracy of these data for stroke and its main pathological types (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage), determining the optimum codes for case identification.We sought studies published from 1990-November 2013, which compared coded data from death certificates, hospital admissions or primary care with a reference standard for stroke or its pathological types. We extracted information on a range of study characteristics and assessed study quality with the Quality Assessment of Diagnostic Studies tool (QUADAS-2). To assess accuracy, we extracted data on positive predictive values (PPV) and-where available-on sensitivity, specificity, and negative predictive values (NPV).37 of 39 eligible studies assessed accuracy of International Classification of Diseases (ICD)-coded hospital or death certificate data. They varied widely in their settings, methods, reporting, quality, and in the choice and accuracy of codes. Although PPVs for stroke and its pathological types ranged from 6-97%, appropriately selected, stroke-specific codes (rather than broad cerebrovascular codes) consistently produced PPVs >70%, and in several studies >90%. The few studies with data on sensitivity, specificity and NPV showed higher sensitivity of hospital versus death certificate data for stroke, with specificity and NPV consistently >96%. Few studies assessed either primary care data or combinations of data sources.Particular stroke-specific codes can yield high PPVs (>90%) for stroke/stroke types. Inclusion of primary care data and combining data sources should improve accuracy in large epidemiological studies, but there is limited published information about these strategies