MARIA M4:clinical evaluation of a prototype ultrawideband radar scanner for breast cancer detection

A microwave imaging system has been developed as a clinical diagnostic tool operating in the 3- to 8-GHz region using multistatic data collection. A total of 86 patients recruited from a symptomatic breast care clinic were scanned with a prototype design. The resultant three-dimensional images have been compared “blind” with available ultrasound and mammogram images to determine the detection rate. Images show the location of the strongest signal, and this corresponded in both older and younger women, with sensitivity of [Formula: see text] , which was found to be maintained in dense breasts. The pathway from clinical prototype to clinical evaluation is outlined

Genetic diversity within and between British and Irish breeds: the maternal and paternal history of native ponies.

The UK and Ireland have many native pony breeds with historical and cultural importance as well as being a source of uncharacterized genetic diversity. However, there is a lack of comprehensive research investigating their genetic diversity and phylogenetic interrelationships. Many studies contain a limited number of pony breeds or small sample sizes for these breeds. This may result in erroneous grouping of pony breeds that otherwise have intricate interrelationships with each other and are not evaluated correctly when placed as a token subset of a larger dataset. This is the first study that specifically investigates the genetic diversity within and between British and Irish native pony breeds using large sample numbers from locations of their native origin. This study used a panel of microsatellite markers and sequence analysis of the mitochondrial control region to analyze the genetic diversity within and between 11 pony breeds from Britain and Ireland. A large dataset was collected (a total of 485 animals were used for mtDNA analysis and 450 for microsatellite analysis), and previously published data were used to place the British and Irish ponies in a global context. The native ponies of Britain and Ireland were found to have had a complex history, and the interrelationships between the breeds were revealed. Overall, high levels of genetic diversity were maintained in native breeds, although some reduction was evident in small or isolated populations (Shetland, Carneddau, and Section C). Unusual mitochondrial diversity distribution patterns were apparent for the Carneddau and Dartmoor, although among breeds and global haplogroups there was a high degree of haplotype sharing evident, well-represented within British and Irish ponies. Ancestral maternal diversity was maintained by most populations, particularly the Fells and Welsh ponies, which exhibited rare and ancient lineages. The maternal and paternal histories of the breeds are distinct, with male-biased crossings between native breeds, and other shared influences, likely Arabs and Thoroughbreds, are apparent. The data generated herein provide valuable information to guide and implement the conservation of increasingly rare native genetic resources

Banking from Leeds, not London: regional strategy and structure at the Yorkshire Bank, 1859–1952

Industrial philanthropist Edward Akroyd created the Yorkshire Penny Savings Bank in 1859. Despite competition from the Post Office Savings Bank after 1861 and a serious reserve problem in 1911, it sustained his overall strategy to become a successful regional bank. Using archival and contemporary sources to build on recent scholarship illustrating how savings banks were integrated into local economies and the complementary roles of philanthropy and paternalism, we analyse an English regional bank's strategy, including an assessment of strategic innovation, ownership changes and management structure. This will demonstrate that the founder's vision continued, even though the 1911 crisis radically altered both strategy and structure

Detecting genetic regions associated with height in the native ponies of the British Isles by using high density SNP genotyping

Height is an important characteristic in the equine industry, although little is known about its genetic control in native British breeds of ponies. This study aimed to map QTL data with the withers height in four pony breeds native to the British Isles, including two different sections within Welsh Cobs. In this study, a genome-wide analysis approach using the Illumina Equine SNP50 Infinium BeadChip was applied to 105 ponies and cobs. Analysis identified 222 highly significant height-associated SNPs (P < 10-5), among which three SNPs on ECA9 have also been previously reported elsewhere. The highest number of significant SNPs associated to height in the native British horses were located on ECA1, ECA8 and ECA16

Neutralizing monoclonal antibodies recognize antigenic variants among isolates of infectious hematopoietic necrosis virus

Neutralizing monoclonal antibodies were developed against strains of infectious hematopoietic necrosis virus (IHNV) from steelhead trout Salmo gairdneri in the Deschutes River of Oregon, chinook salmon Oncorhynchus tshawytscha in the Sacramento River of California, and rainbow trout Salmo gairdneri reared in the Hagerman Valley of Idaho, USA. These antibodies were tested for neutralization of 12 IHNV isolates obtained from salmonids in Japan, Alaska, Washington, Oregon, California, and Idaho. The antibodies recognized antigenic variants among the isolates and could be used to separate the viruses into 4 groups. The members of each group tended to be related by geographic area rather than by source host species, virulence, or date of isolation.Keywords: infectious hematopoietic necrosis virus, neutralization, immunology, monoclonal antibodies, fish disease

CERN West Area neutrino facility beam line alignment

This papers describes the alignment of the West Area Neutrino Beam Line at CERN to the two neutrino experiments CHORUS and NOMAD. The T9 neutrino (n) target position and the position of the magnetic horn were optimised using the secondary muon intensity profiles from the muon pits in the shielding. In the experiments the improved geometry provides a better centred beam (< 5 cm) and a measured increase in the n flux of 8%

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Volcanic glass from the 1.8 ka Taupō eruption (New Zealand) detected in Antarctic ice at ~ 230 CE.

Chemical anomalies in polar ice core records are frequently linked to volcanism; however, without the presence of (crypto)tephra particles, links to specific eruptions remain speculative. Correlating tephras yields estimates of eruption timing and potential source volcano, offers refinement of ice core chronologies, and provides insights into volcanic impacts. Here, we report on sparse rhyolitic glass shards detected in the Roosevelt Island Climate Evolution (RICE) ice core (West Antarctica), attributed to the 1.8 ka Taupō eruption (New Zealand)-one of the largest and most energetic Holocene eruptions globally. Six shards of a distinctive geochemical composition, identical within analytical uncertainties to proximal Taupō glass, are accompanied by a single shard indistinguishable from glass of the ~25.5 ka Ōruanui supereruption, also from Taupō volcano. This double fingerprint uniquely identifies the source volcano and helps link the shards to the climactic phase of the Taupō eruption. The englacial Taupō-derived glass shards coincide with a particle spike and conductivity anomaly at 278.84 m core depth, along with trachytic glass from a local Antarctic eruption of Mt. Melbourne. The assessed age of the sampled ice is 230 ± 19 CE (95% confidence), confirming that the published radiocarbon wiggle-match date of 232 ± 10 CE (2 SD) for the Taupō eruption is robust

Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing

OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell neoplasm, requiring the integration of clinical examination, laboratory and radiological investigations for diagnosis. Detection and isotypic identification of the monoclonal protein(s) and measurement of other relevant biomarkers in serum and urine are pivotal analyses. However, occasionally this approach fails to characterize complex protein signatures. Here we describe the development and application of next generation mass spectrometry (MS) techniques, and a novel adaptation of immunofixation, to interrogate non-canonical monoclonal immunoproteins. METHODS: Immunoprecipitation immunofixation (IP-IFE) was performed on a Sebia Hydrasys Scan2. Middle-down de novo sequencing and native MS were performed with multiple instruments (21T FT-ICR, Q Exactive HF, Orbitrap Fusion Lumos, and Orbitrap Eclipse). Post-acquisition data analysis was performed using Xcalibur Qual Browser, ProSight Lite, and TDValidator. RESULTS: We adapted a novel variation of immunofixation electrophoresis (IFE) with an antibody-specific immunosubtraction step, providing insight into the clonal signature of gamma-zone monoclonal immunoglobulin (M-protein) species. We developed and applied advanced mass spectrometric techniques such as middle-down de novo sequencing to attain in-depth characterization of the primary sequence of an M-protein. Quaternary structures of M-proteins were elucidated by native MS, revealing a previously unprecedented non-covalently associated hetero-tetrameric immunoglobulin. CONCLUSIONS: Next generation proteomic solutions offer great potential for characterizing complex protein structures and may eventually replace current electrophoretic approaches for the identification and quantification of M-proteins. They can also contribute to greater understanding of MM pathogenesis, enabling classification of patients into new subtypes, improved risk stratification and the potential to inform decisions on future personalized treatment modalities