Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data

Does preexisting or treatment-emergent autoimmunity increase the risk of subsequent autoimmune disease in individuals with relapsing-remitting multiple sclerosis (MS) after alemtuzumab? In the extended phase 2/3 trials, 34/96 (35.4%) patients with and 395/1120 (35.3%) without preexisting autoimmunity developed non-MS autoimmunity. Thyroid autoimmunity after alemtuzumab courses 1 or 2 did not increase subsequent non-thyroid autoimmune adverse events. Therefore, autoimmune disease before or after alemtuzumab treatment does not predict autoimmunity after further courses, so should not preclude adequate alemtuzumab dosing to control MS. Finally, post-marketing safety data contribute toward a full record of the alemtuzumab benefit/risk profile for the MS field.

The public health approach to suicide prevention in Ireland

This article provides an overview of the public health approach to suicide in Ireland. The authors provide detail on the current suicide prevention strategy in Ireland, Connecting for Life, which is a whole-of-government, systemic, multicomponent national strategy. As the strategy enters its final extended phase of implementation over the period 2020–2024, the public health elements of Connecting for Life are presented, including the population level and more targeted approaches. The findings of an interim review of the strategy are discussed, in addition to the local and national implementation structures which are in place to assist implementation and monitoring of the strategy.

Theta rhythmicity governs human behavior and hippocampal signals during memory-dependent tasks

Memory formation and reinstatement are thought to lock to the hippocampal theta rhythm, predicting that encoding and retrieval processes appear rhythmic themselves. Here, we show that rhythmicity can be observed in behavioral responses from memory tasks, where participants indicate, using button presses, the timing of encoding and recall of cue-object associative memories. We find no evidence for rhythmicity in button presses for visual tasks using the same stimuli, or for questions about already retrieved objects. The oscillations for correctly remembered trials center in the slow theta frequency range (1-5 Hz). Using intracranial EEG recordings, we show that the memory task induces temporally extended phase consistency in hippocampal local field potentials at slow theta frequencies, but significantly more for remembered than forgotten trials, providing a potential mechanistic underpinning for the theta oscillations found in behavioral responses.

A Modified Wavenumber Algorithm of Multi-Layered Structures with Oblique Incidence Based on Full-Matrix Capture

Full-matrix capture (FMC)-based ultrasonic imaging provides good sensitivity to small defects in non-destructive testing and has gradually become a mainstream research topic. Many corresponding algorithms have been developed, e.g., the total focusing method (TFM). However, the efficiency of the TFM is limited, especially in multi-layered structures. Although the appearance of wavenumber algorithms, such as extended phase-shift migration (EPSM) methods, has improved imaging efficiency, these methods cannot be applied to cases with oblique incidence. Therefore, a modified wavenumber method for full-matrix imaging of multi-layered structures with oblique array incidence is proposed. This method performs a coordinate rotation in the frequency domain to adapt it to the oblique incidence. It then utilizes wave-field extrapolation to migrate the transmitting and receiving wave field to each imaging line, and a correlation imaging condition is used to reconstruct a total focused image. The proposed method can deal with any incident angle without precision loss. Moreover, it inherits the computational efficiency advantages of the wavenumber algorithms. The simulation and experimental results show that the proposed method performs better in terms of accuracy and efficiency than the TFM. Specifically, it is nearly 60 times faster than the TFM when processing an FMC dataset with a size of 4096 × 64 × 64.

Stratigraphy, facies architecture and emplacement history of the c. 3.6 ka B.P. Ngatoro Formation on the eastern flanks of Egmont Volcano, western North Island, New Zealand

<p>The Ngatoro Formation is an extensive volcaniclastic deposit distributed on the eastern lower flanks of Egmont Volcano, central North Island, New Zealand. Formally identified by Neall (1979) this deposit was initially attributed to an Egmont sourced water-supported mass flow event c. 3, 600 ¹⁴C years B.P. The Ngatoro Formation was subsequently described by Alloway (1989) as a single debris flow deposit closely associated with the deposition of the underlying Inglewood Tephra (c. 3,600 ¹⁴C yrs B.P) that had laterally transformed into a hyperconcentrated- to- flood flow deposit. Such water-supported mass flows have been well documented on volcanoes both within New Zealand (i.e. Mt Ruapehu) and elsewhere around the world (i.e. Mt Merapi, Central Java and Mt St Helens, Washington). This thesis comprises field mapping, stratigraphic descriptions, field and laboratory grain size and shape analysis, tephrochronology and palaeomagnetic analysis with the aim of refining the stratigraphy, facies architecture and emplacement history of the c. 3,600 ¹⁴C yrs B.P. Ngatoro Formation. This study has found that the Ngatoro Formation has a highly variable and complex emplacement history as evidenced by the rapid textural changes with increasing distance from the modern day Egmont summit. The Ngatoro Formation comprises two closely spaced mass flow events whose flow and emplacement characteristics have undergone both proximal to distal and axial to marginal transformations. On surfaces adjacent to the Manganui Valley on the deeply incised flanks of Egmont Volcano, the Ngatoro Formation is identified as overbank surge deposits whereas at the boundary of Egmont National Park it occurs as massive, pebble- to boulder-rich debris flow deposits. At intermediate to distal distances (17-23 km from the modern Egmont summit) the Ngatoro Formation occurs as a sequence of multiple coalescing dominantly sandy textured hyperconcentrated flow deposits. The lateral and longitudinal textural variability in the Ngatoro Formation reflects downstream transformation from gas-supported block-and-ash flows to water-supported debris flows, then subsequently to turbulent pebbly-sand dominated hyperconcentrated flows. Palaeomagnetic temperature estimates for the Ngatoro Formation at two sites (Vickers and Surrey Road Quarries, c. 10 km from the present day Egmont summit) indicate clast incorporation temperatures of c. 300°C and emplacement temperatures of c. 200°C. The elevated emplacement temperatures supported by the Ngatoro Formation’s coarse textured, monolithologic componentry suggest non-cohesive emplacement of block-and-ash flow debris generated by the sequential gravitational collapse of an effusive lava dome after the paroxysmal Inglewood eruptive event (c. 3,600 ¹⁴C yrs B.P.). The occurrence of a prominent intervening paleosol between these two events suggest that they are not part of the same eruptive phase but rather, the latter is a product of a previously unrecognised extended phase of the Inglewood eruptive event. This study recognises the potential for gravitational dome collapse, the generation of block-and-ash flows and their lateral transformation to water-support mass flows (debris, hyperconcentrated and stream flows) occurring in years to decades following from the main eruptive phase. This insight has implications with respect to the evaluation of post-eruptive hazards and risk.</p>

Stratigraphy, facies architecture and emplacement history of the c. 3.6 ka B.P. Ngatoro Formation on the eastern flanks of Egmont Volcano, western North Island, New Zealand

<p>The Ngatoro Formation is an extensive volcaniclastic deposit distributed on the eastern lower flanks of Egmont Volcano, central North Island, New Zealand. Formally identified by Neall (1979) this deposit was initially attributed to an Egmont sourced water-supported mass flow event c. 3, 600 ¹⁴C years B.P. The Ngatoro Formation was subsequently described by Alloway (1989) as a single debris flow deposit closely associated with the deposition of the underlying Inglewood Tephra (c. 3,600 ¹⁴C yrs B.P) that had laterally transformed into a hyperconcentrated- to- flood flow deposit. Such water-supported mass flows have been well documented on volcanoes both within New Zealand (i.e. Mt Ruapehu) and elsewhere around the world (i.e. Mt Merapi, Central Java and Mt St Helens, Washington). This thesis comprises field mapping, stratigraphic descriptions, field and laboratory grain size and shape analysis, tephrochronology and palaeomagnetic analysis with the aim of refining the stratigraphy, facies architecture and emplacement history of the c. 3,600 ¹⁴C yrs B.P. Ngatoro Formation. This study has found that the Ngatoro Formation has a highly variable and complex emplacement history as evidenced by the rapid textural changes with increasing distance from the modern day Egmont summit. The Ngatoro Formation comprises two closely spaced mass flow events whose flow and emplacement characteristics have undergone both proximal to distal and axial to marginal transformations. On surfaces adjacent to the Manganui Valley on the deeply incised flanks of Egmont Volcano, the Ngatoro Formation is identified as overbank surge deposits whereas at the boundary of Egmont National Park it occurs as massive, pebble- to boulder-rich debris flow deposits. At intermediate to distal distances (17-23 km from the modern Egmont summit) the Ngatoro Formation occurs as a sequence of multiple coalescing dominantly sandy textured hyperconcentrated flow deposits. The lateral and longitudinal textural variability in the Ngatoro Formation reflects downstream transformation from gas-supported block-and-ash flows to water-supported debris flows, then subsequently to turbulent pebbly-sand dominated hyperconcentrated flows. Palaeomagnetic temperature estimates for the Ngatoro Formation at two sites (Vickers and Surrey Road Quarries, c. 10 km from the present day Egmont summit) indicate clast incorporation temperatures of c. 300°C and emplacement temperatures of c. 200°C. The elevated emplacement temperatures supported by the Ngatoro Formation’s coarse textured, monolithologic componentry suggest non-cohesive emplacement of block-and-ash flow debris generated by the sequential gravitational collapse of an effusive lava dome after the paroxysmal Inglewood eruptive event (c. 3,600 ¹⁴C yrs B.P.). The occurrence of a prominent intervening paleosol between these two events suggest that they are not part of the same eruptive phase but rather, the latter is a product of a previously unrecognised extended phase of the Inglewood eruptive event. This study recognises the potential for gravitational dome collapse, the generation of block-and-ash flows and their lateral transformation to water-support mass flows (debris, hyperconcentrated and stream flows) occurring in years to decades following from the main eruptive phase. This insight has implications with respect to the evaluation of post-eruptive hazards and risk.</p>

A unifying view on extended phase graphs and Bloch simulations for quantitative MRI

Quantitative MRI methods and learning-based algorithms require exact forward simulations. One critical factor to correctly describe magnetization dynamics is the effect of slice-selective RF pulses. While contemporary simulation techniques correctly capture their influence, they only provide final magnetization distributions, require to be run for each parameter set separately, and make it hard to derive general theoretical conclusions and to generate a fundamental understanding of echo formation in the presence of slice-profile effects. This work aims to provide a mathematically exact framework, which is equally intuitive as extended phase graphs (EPGs), but also considers slice-profiles through their natural spatial representation. We show, through an analytical, hybrid Bloch-EPG formalism, that the spatially-resolved EPG approach allows to exactly predict the signal dependency on off-resonance, spoiling moment, microscopic dephasing, and echo time. We also demonstrate that our formalism allows to use the same phase graph to simulate both gradient-spoiled and balanced SSFP-based MR sequences. We present a derivation of the formalism and identify the connection to existing methods, i.e. slice-selective Bloch, slice-selective EPG, and the partitioned EPG. As a use case, the proposed hybrid Bloch-EPG framework is applied to MR Fingerprinting.