A new prevalence study of multiple sclerosis in Orkney, Shetland and Aberdeen city

Peer reviewedPostprin

High resolution AMI Large Array imaging of spinning dust sources: spatially correlated 8 micron emission and evidence of a stellar wind in L675

We present 25 arcsecond resolution radio images of five Lynds Dark Nebulae (L675, L944, L1103, L1111 & L1246) at 16 GHz made with the Arcminute Microkelvin Imager (AMI) Large Array. These objects were previously observed with the AMI Small Array to have an excess of emission at microwave frequencies relative to lower frequency radio data. In L675 we find a flat spectrum compact radio counterpart to the 850 micron emission seen with SCUBA and suggest that it is cm-wave emission from a previously unknown deeply embedded young protostar. In the case of L1246 the cm-wave emission is spatially correlated with 8 micron emission seen with Spitzer. Since the MIR emission is present only in Spitzer band 4 we suggest that it arises from a population of PAH molecules, which also give rise to the cm-wave emission through spinning dust emission.Comment: accepted MNRA

Hybridization of DNA probes to A. marginale isolates from different sources and detection in Dermacentor andersoni ticks

DNA from the Washington, South-Idaho, Virginia and Florida isolates of Anaplasma marginale was hybridized to probes specific for Anaplasma centrale and A. marginale. The A. centrale probes AC-2 and AC-4 hybridized to identical bands on all of these isolates. The hybridization pattern suggests that the Virginia, Florida and the South African isolates are similar. A number of bands were obtained with the Washington isolate which differed from those obtained with the other isolates. Probe AC-2 could be developed to identify relatedness among Anaplasma isolates. Probe AC-2 detected A. marginale DNA in midgut material from infected Dermacentor andersoni ticks. No hybridization was obtained with DNA from salivary gland tissues from these infected ticks.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.lmchunu2014mn201

Quality of life of parents with children living at home: when one parent has cancer

Goals of work This study examined the quality of life (QoL) of cancer patients diagnosed 1-5 years previously and their spouses, with children 4-18 years living at home. Relationships between parents' QoL and the children's functioning were explored. Patients and methods 166 cancer patients and their spouses provided information on their QoL (RAND-36) and on their children's functioning (Child Behavior Checklist). Main results Male and female patients scored similarly to a norm population on five domains. Patients' QoL was clinically relevantly and/or statistically lower on social functioning, role limitations because of physical problems, and vitality than the norm. Male spouses' QoL was comparable to the norm. However, female spouses reported better physical functioning but more social problems. QoL varied according to type of cancer, treatment intensity, and recurrence. Using the QoL composite scores, a significant relationship was found between patients' psychosocial and physical functioning and spouses' psychosocial functioning. Patients' psychosocial functioning correlated moderately strongly to weakly with their reports of their younger children's and adolescents' functioning; physical functioning correlated only weakly with adolescents' functioning. The patients' functioning related weakly to moderately strongly to adolescents' self-reports of functioning. Spouses' psychosocial functioning weakly related to their and adolescents' reports of adolescents' functioning. Conclusion Cancer patients' QoL 1-5 years after diagnosis was decreased in three of eight domains; their spouses seem to be doing well. Parents' physical and psychosocial functioning related weakly to moderately strongly to their children's functioning, depending on the child's age and information source. The patients' functioning related more strongly to the children's functioning than the spouses' did

AMI observations of Lynds Dark Nebulae: further evidence for anomalous cm-wave emission

Observations at 14.2 to 17.9 GHz made with the AMI Small Array towards fourteen Lynds Dark Nebulae with a resolution of 2' are reported. These sources are selected from the SCUBA observations of Visser et al. (2001) as small angular diameter clouds well matched to the synthesized beam of the AMI Small Array. Comparison of the AMI observations with radio observations at lower frequencies with matched uv-plane coverage is made, in order to search for any anomalous excess emission which can be attributed to spinning dust. Possible emission from spinning dust is identified as a source within a 2' radius of the Scuba position of the Lynds dark nebula, exhibiting an excess with respect to lower frequency radio emission. We find five sources which show a possible spinning dust component in their spectra. These sources have rising spectral indices in the frequency range 14.2--17.9 GHz. Of these five one has already been reported, L1111, we report one new definite detection, L675, and three new probable detections (L944, L1103 and L1246). The relative certainty of these detections is assessed on the basis of three criteria: the extent of the emission, the coincidence of the emission with the Scuba position and the likelihood of alternative explanations for the excess. Extended microwave emission makes the likelihood of the anomalous emission arising as a consequence of a radio counterpart to a protostar or a proto-planetary disk unlikely. We use a 2' radius in order to be consistent with the IRAS identifications of dark nebulae (Parker 1988), and our third criterion is used in the case of L1103 where a high flux density at 850 microns relative to the FIR data suggests a more complicated emission spectrum.Comment: submitted MNRA

AMI observations of unmatched Planck ERCSC LFI sources at 15.75 GHz

The Planck Early Release Compact Source Catalogue includes 26 sources with no obvious matches in other radio catalogues (of primarily extragalactic sources). Here we present observations made with the Arcminute Microkelvin Imager Small Array (AMI SA) at 15.75 GHz of the eight of the unmatched sources at declination > +10 degrees. Of the eight, four are detected and are associated with known objects. The other four are not detected with the AMI SA, and are thought to be spurious.Comment: 6 pages, 5 figures, 4 table

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke

AMI Large Array radio continuum observations of Spitzer c2d small clouds and cores

We perform deep 1.8 cm radio continuum imaging towards thirteen protostellar regions selected from the Spitzer c2d small clouds and cores programme at high resolution (25") in order to detect and quantify the cm-wave emission from deeply embedded young protostars. Within these regions we detect fifteen compact radio sources which we identify as radio protostars including two probable new detections. The sample is in general of low bolometric luminosity and contains several of the newly detected VeLLO sources. We determine the 1.8 cm radio luminosity to bolometric luminosity correlation, L_rad -L_bol, for the sample and discuss the nature of the radio emission in terms of the available sources of ionized gas. We also investigate the L_rad-L_IR correlation and suggest that radio flux density may be used as a proxy for the internal luminosity of low luminosity protostars.Comment: submitted MNRA

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