Voice banking for individuals living with MND : a service review

BACKGROUND: Voice banking allows those living with Motor Neurone Disease (MND) to create a personalised synthetic voice. Little is known about how best to support this process. OBJECTIVE: To review a dedicated voice banking service with the aim of informing service development. METHOD: A service review of existing health records from neurological services in Sheffield, UK, carried out retrospectively and covering 2018 and 2019. Case notes were reviewed to extract information about use of communication aids, offer of voice banking, and use of synthesised speech. Responses to a routine follow up survey were also collated. RESULTS: Less than half of the clients whose notes were reviewed had been informed about voice banking, one in four had completed the voice banking process, around half were using communication aids, and one in ten were using their personalised synthetic voice on a communication aid. The time taken to complete the process had a large variation. Those completing the process viewed the personalised voices positively and all were used when created. Support from professionals was noted by some as being key. CONCLUSIONS: Voice banking services should be more widely promoted to ensure that individuals can consider voice banking prior to changes in their speech. Research studies should inform how and when those living with MND are introduced to voice banking

Megasequence architecture of Taranaki, Wanganui, and King Country basins and Neogene progradation of two continental margin wedges across western New Zealand.

Taranaki, Wanganui and King Country basins (formerly North Wanganui Basin) have been regarded as discrete basins, but they contain a very similar Neogene sedimentary succession and much of their geological history is held in common. Analysis of the stratigraphic architecture of the fill of each basin reveals the occurrence of four 2nd order megasequences of tectonic origin. The oldest is the early-early Miocene (Otaian Stage) Mahoenui Group/megasequence, followed by the late-early Miocene (Altonian Stage) Mokau Group/megasequence (King Country Basin), both of which correspond to the lower part of the Manganui Formation in Taranaki Basin. The third is the middle to late Miocene Whangamomona Group/megasequence, and the fourth is the latest Miocene-Pleistocene Rangitikei Supergroup/megasequence, both represented in the three basins. Higher order sequences (4th, 5th, 6th), having a eustatic origin, are evident in the Whangamomona and Rangitikei megasequences, particularly those of 5th order with 41 ka periodicity. The distribution of the megasequences are shown in a series of cross-section panels built-up from well -to-well correlations, complemented by time-stratigraphic cross-sections. The base of each megasequence is marked by marine flooding and represents a discrete phase in basin development. For the first megasequence this corresponded to rapid subsidence of the King Country Basin in a compressional setting and basement overthrusting on the Taranaki Fault, with the rapid introduction of terrigenous sediment during transgression. The Mahoenui megasequence accumulated mostly at bathyal depths; no regressive deposits are evident, having been eroded during subsequent uplift. The second (Mokau) megasequence accumulated during reverse movement on the Ohura Fault, formation of the Tarata Thrust Zone, and onlap of the basement block between the Taranaki Fault and the Patea-Tongaporutu-Herangi High (PTH). The Whangamomona megasequence accumulated during extensive reflooding of King Country Basin, onlap of the PTH High and of basement in the Wanganui Basin. This is an assymetrical sequence with a thin transgressive part (Otunui Formation) and a thick regressive part (Mount Messenger to Matemateaonga Formations). It represents the northward progradation of a continental margin wedge with bottom-set, slope-set and top-set components through Wanganui and King Country basins, with minor progradation over the PTH High and into Taranaki Basin. The Rangitikei megasequence is marked by extensive flooding at its base (Tangahoe Mudstone) and reflects the pull-down of the main Wanganui Basin depocentre. This megasequence comprises a second progradational margin wedge, which migrated on two fronts, one northward through Wanganui Basin and into King Country Basin, and a second west of the PTH High, through the Toru Trough and into the Central and Northern Grabens of Taranaki Basin and on to the Western Platform as the Giant Foresets Formation, thereby building up the modern shelf and slope. Fifth and 6th order sequences are well expressed in the shelf deposits (top-sets) of the upper parts of the Whangamomona and Rangitikei megasequences. They typically have a distinctive sequence architecture comprising shellbed (TST), siltstone (HST) and sandstone (RST) beds. Manutahi-1, which was continuously cored, provides calibration of this sequence architecture to wireline log character, thereby enabling shelf deposits to be mapped widely in the subsurface via the wireline data for hydrocarbon exploration holes. Similar characterization of slope-sets and bottom-sets is work ongoing. The higher order (eustatic) sequences profoundly influenced the local reservoir architecture and seal properties of formations, whereas the megasequence progradation has been responsible for the regional hydrocarbon maturation and migration. Major late tilting, uplift and erosion affected all three basins and created a regional high along the eastern Margin of Taranaki Basin, thereby influencing the migration paths of hydrocarbons sourced deeper in the basin and allowing late charge of structural and possibly stratigraphic traps

Megasequence architecture of Taranaki, Wanganui, and King Country basins and Neogene progradation of two continental margin wedges across western New Zealand.

Taranaki, Wanganui and King Country basins (formerly North Wanganui Basin) have been regarded as discrete basins, but they contain a very similar Neogene sedimentary succession and much of their geological history is held in common. Analysis of the stratigraphic architecture of the fill of each basin reveals the occurrence of four 2nd order megasequences of tectonic origin. The oldest is the early-early Miocene (Otaian Stage) Mahoenui Group/megasequence, followed by the late-early Miocene (Altonian Stage) Mokau Group/megasequence (King Country Basin), both of which correspond to the lower part of the Manganui Formation in Taranaki Basin. The third is the middle to late Miocene Whangamomona Group/megasequence, and the fourth is the latest Miocene-Pleistocene Rangitikei Supergroup/megasequence, both represented in the three basins. Higher order sequences (4th, 5th, 6th), having a eustatic origin, are evident in the Whangamomona and Rangitikei megasequences, particularly those of 5th order with 41 ka periodicity. The distribution of the megasequences are shown in a series of cross-section panels built-up from well -to-well correlations, complemented by time-stratigraphic cross-sections. The base of each megasequence is marked by marine flooding and represents a discrete phase in basin development. For the first megasequence this corresponded to rapid subsidence of the King Country Basin in a compressional setting and basement overthrusting on the Taranaki Fault, with the rapid introduction of terrigenous sediment during transgression. The Mahoenui megasequence accumulated mostly at bathyal depths; no regressive deposits are evident, having been eroded during subsequent uplift. The second (Mokau) megasequence accumulated during reverse movement on the Ohura Fault, formation of the Tarata Thrust Zone, and onlap of the basement block between the Taranaki Fault and the Patea-Tongaporutu-Herangi High (PTH). The Whangamomona megasequence accumulated during extensive reflooding of King Country Basin, onlap of the PTH High and of basement in the Wanganui Basin. This is an assymetrical sequence with a thin transgressive part (Otunui Formation) and a thick regressive part (Mount Messenger to Matemateaonga Formations). It represents the northward progradation of a continental margin wedge with bottom-set, slope-set and top-set components through Wanganui and King Country basins, with minor progradation over the PTH High and into Taranaki Basin. The Rangitikei megasequence is marked by extensive flooding at its base (Tangahoe Mudstone) and reflects the pull-down of the main Wanganui Basin depocentre. This megasequence comprises a second progradational margin wedge, which migrated on two fronts, one northward through Wanganui Basin and into King Country Basin, and a second west of the PTH High, through the Toru Trough and into the Central and Northern Grabens of Taranaki Basin and on to the Western Platform as the Giant Foresets Formation, thereby building up the modern shelf and slope. Fifth and 6th order sequences are well expressed in the shelf deposits (top-sets) of the upper parts of the Whangamomona and Rangitikei megasequences. They typically have a distinctive sequence architecture comprising shellbed (TST), siltstone (HST) and sandstone (RST) beds. Manutahi-1, which was continuously cored, provides calibration of this sequence architecture to wireline log character, thereby enabling shelf deposits to be mapped widely in the subsurface via the wireline data for hydrocarbon exploration holes. Similar characterization of slope-sets and bottom-sets is work ongoing. The higher order (eustatic) sequences profoundly influenced the local reservoir architecture and seal properties of formations, whereas the megasequence progradation has been responsible for the regional hydrocarbon maturation and migration. Major late tilting, uplift and erosion affected all three basins and created a regional high along the eastern Margin of Taranaki Basin, thereby influencing the migration paths of hydrocarbons sourced deeper in the basin and allowing late charge of structural and possibly stratigraphic traps

Neogene stratigraphic architecture and tectonic evolution of Wanganui, King Country, and eastern Taranaki Basins, New Zealand

Analysis of the stratigraphic architecture of the fills of Wanganui, King Country, and eastern Taranaki Basins reveals the occurrence of five 2nd order Late Paleocene and Neogene sequences of tectonic origin. The oldest is the late Eocene-Oligocene Te Kuiti Sequence, followed by the early-early Miocene (Otaian) Mahoenui Sequence, followed by the late-early Miocene (Altonian) Mokau Sequence, all three in King Country Basin. The fourth is the middle Miocene to early Pliocene Whangamomona Sequence, and the fifth is the middle Pliocene-Pleistocene Rangitikei Sequence, both represented in the three basins. Higher order sequences (4th, 5th, 6th) with a eustatic origin occur particularly within the Whangamomona and Rangitikei Sequences, particularly those of 6th order with 41 000 yr periodicity

Active local oscillator power stabilization for a hot electron bolometer heterodyne receiver

We report on the application of a new technique for actively stabilizing the power of a far infrared gas laser as the local oscillator (LO) in a superconducting hot electron bolometer (HEB) heterodyne receiver system at 2.5 THz. The technique utilizes PID feedback control of the local oscillator intensity by means of a voice-coil based swing arm actuator placed in the beam path. The HEB itself is used as a direct detector to measure incident LO power whilst simultaneously continuing to function as heterodyne mixer. Results presented here demonstrate a factor of 50 improvement in the measured total power and spectroscopic Allan variance time. Allan times of 30 seconds and 25 seconds respectively are shown for large and small area HEB's with a measured effective noise fluctuation bandwidth of 12 MHz. The technique is versatile and can be applied to any LO source and at any LO frequency

A Multidomain Adhesion Protein Family Expressed in Plasmodium falciparum Is Essential for Transmission to the Mosquito

The recent sequencing of several apicomplexan genomes has provided the opportunity to characterize novel antigens essential for the parasite life cycle that might lead to the development of new diagnostic and therapeutic markers. Here we have screened the Plasmodium falciparum genome sequence for genes encoding extracellular multidomain putative adhesive proteins. Three of these identified genes, named PfCCp1, PfCCp2, and PfCCp3, have multiple adhesive modules including a common Limulus coagulation factor C domain also found in two additional Plasmodium genes. Orthologues were identified in the Cryptosporidium parvum genome sequence, indicating an evolutionary conserved function. Transcript and protein expression analysis shows sexual stage–specific expression of PfCCp1, PfCCp2, and PfCCp3, and cellular localization studies revealed plasma membrane–associated expression in mature gametocytes. During gametogenesis, PfCCps are released and localize surrounding complexes of newly emerged microgametes and macrogametes. PfCCp expression markedly decreased after formation of zygotes. To begin to address PfCCp function, the PfCCp2 and PfCCp3 gene loci were disrupted by homologous recombination, resulting in parasites capable of forming oocyst sporozoites but blocked in the salivary gland transition. Our results describe members of a conserved apicomplexan protein family expressed in sexual stage Plasmodium parasites that may represent candidates for subunits of a transmission-blocking vaccine

Immunogenicity of a universal HIV-1 vaccine vectored by DNA, MVA and CHADV-63 in a Phase I/IIA clinical trial

Background The major challenge facing both antibody and T cell-eliciting vaccines against HIV-1 is the extreme variability of the HIV-1 genome: a successful vaccine has to effectively target diverse HIV-1 strains circulating in the population and then must deal with ongoing virus escape in infected individuals. To address these issues, we assembled a vaccine immunogen HIVconsv from the functionally most conserved regions (not epitopes) of the HIV-1 proteome. Methods A gene coding for the HIVconsv immunogen was inserted into plasmid DNA (D), modified vaccinia virus Ankara (MVA; M) and non-replicating adenovirus of a chimpanzee origin ChAdV-63 (C). Currently, combined heterologous prime-boost regimens of these vaccines, namely CM, DDDCM and DDDMC, are being evaluated in a phase I/IIa trial HIV-CORE002 in healthy HIV-1/2-negative volunteers in Oxford. Results Preliminary data indicate that the vaccines are well tolerated and show high immunogenicity. Following the CM regimen, vaccine-induced T cell frequencies reached a median of 5150 (range 1475 to 16495) SFU/106 PMBC ex vivo one week post MVA vaccination. DNA priming increased subsequent T cell responses to ChAdV-63 vaccination (median: C 577 and DDDC 1328 SFU/106 PBMC) and ELISpot responses again peaked 1 week following MVA (median 4500; range 2260-7960 SFU/106 PBMC). Matrix analyses of the participants following CM vaccination showed that T cells responded to a range of peptides across the length of HIVconsv. The CM regimen elicited IFN-γ in both CD4+ and CD8+ T cell subsets and polyfunctional (IFN-γ & TNF-α) responses to HIVconsv peptides. Conclusion Presented data will be very much work in progress. Nevetheless, the HIVconsv vaccines have so far induced T cell responses superior to other HIV-1 vaccine candidates tested to date. ChAdV-63 is the first adenovirus of chimp origin delivering an HIV-1-derived immunogen that has reached the clinic. The work is supported by Medical Research Council UK

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Nitrous oxide-induced myeloneuropathy: a case series.

BACKGROUND: Nitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but most information comes from small case series. METHODS: We describe 119 patients with N2O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date. RESULTS: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N2O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B12 deficiency (rho (ρ)=0.44, p=0.04). CONCLUSIONS: Preventable neurological harm from N2O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N2O has led to an apparent rise in cases of N2O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment