An investigation into the impact of hydrothermal carbonisation on the suitability of biomass for fuel switching

Biomass has the potential to be a useful low-carbon replacement for coal in a number of applications. Hydrothermal carbonisation (HTC) is a pre-treatment technology which has the potential to alleviate many of the drawbacks of replacing coal with biomass, as it improves many of the fuel properties of biomass. This study was conceived as a means to investigate the impact of HTC on the suitability of biomass for this purpose, and to investigate the chemisty of HTC so that the process could be more deeply understood. HTC experiments were performed using a Parr reactor heated by a sand bath, and numerous analytical techniques were used to investigate the composition and properties of the biocoal produced. Major analytical techniques used include thermogravimetric analysis, elemental analysis, gas chromatography, XRF spectrometry, textural analsyis, and NMR. Devolatilisation of samples in a drop tube furnace was also used so that chars generated under high heating rates equivalent to what is seen in pulverised fuel combustion could be investigated. The impact of HTC process parameters on the yield and composition of biocoal was investigated, and HTC temperuature was found to have the largest impact. Increasing temperature decreased the yield of HTC, and resulted in a biocoal with a lower moisture and volatile matter content, with a higher fixed carbon content. Temperature also had a significant effect on the energy yield and energy densification of biocoal, with increasing temperature decreasing the yield and increasing the densification. A good compromise was found at a midpoint temperature of 225ᵒC, before the energy yield dropped considerably. Anaerobic digestion was calculated to have significant potenital for increasing the energy yield of HTC, especially when there is sinigicant loss of organic matter to the process liquor. The feedstock was also found to have a significant effect on the outcomes of HTC, primarily linked to the biochemical compostion of the feedstock. The removal of alkali and alkaline earth metals was found to have a strong impact on the char reactivity of biocoal, with surface area and biocoal composition providing secondary impact. Biocoal produced from soft wood biomass was shown to have a char reactivity similar to that of high-volatile bituminous coal, but HTC of biomass with higher levels of alkali and alkaline earth metals resued in a biocoal with a reactivity lower than that of the feedstock biomass, but higher than that of high-volatile bituminous coal. A coal-equvalent fuel was generated by torrefaction of soft wood biocoal. The role of water in the aromatisation reactions occuring during HTC in comparison to torrefaction was investigated. Lower levels of aromatisation were seen in HTC than in torrefaction, indicating that the water present in HTC suppresses aromatisation. HTC was found to have little impact on the yield of activated carbon production, and was found to lower the surface area of activated carbon due to deposition of organic matter in the pores of the feedstock

Ringed, Bearded, and Ribbon Seal Vocalizations North of Barrow, Alaska: Seasonal Presence and Relationship with Sea Ice

The acoustic repertoires of ringed, bearded, and ribbon seals are described, along with their seasonal occurrence and relationship to sea ice concentration. Acoustic recordings were made between September and June over three years (2006 – 09) along the continental slope break in the Chukchi Sea, 120 km north-northwest of Barrow, Alaska. Vocalizations of ringed and bearded seals occurred in winter and during periods of 80% – 100% ice cover but were mostly absent during open water periods. The presence of ringed and bearded seal calls throughout winter and spring suggests that some portion of their population is overwintering. Analysis of the repertoire of ringed and bearded seal calls shows seasonal variation. Ringed seal calls are primarily barks in winter and yelps in spring, while bearded seal moans increase during spring. Ribbon seal calls were detected only in the fall of 2008 during the open water period. The repertoire of known ribbon seal vocalizations was expanded to include three additional calls, and two stereotyped call sequences were common. Retrospective analyses of ringed seal recordings from 1982 and ribbon seal recordings from 1967 showed a high degree of stability in call repertoire across large spatial and temporal scales.Le répertoire acoustique des phoques annelés, des phoques barbus et des phoques à bandes sont décrits, de même que leur présence saisonnière et leur rapport avec la concentration de glace de mer. Des enregistrements acoustiques ont été effectués entre septembre et juin sur une période de trois ans (2006 – 2009), le long de la rupture de la pente continentale, dans la mer des Tchouktches, à 120 km au nord-nord-ouest de Barrow, en Alaska. Les vocalisations de phoques annelés et de phoques barbus étaient présentes pendant l’hiver et pendant les périodes où la concentration de glace était de 80 % à 100 %, mais elles se faisaient rares pendant les périodes d’eau libre. La présence des cris de phoques annelés et de phoques barbus tout au long de l’hiver et du printemps suggère qu’une partie de leur population hiverne. L’analyse du répertoire de cris de phoques annelés et de phoques barbus indique une variation saisonnière. L’hiver, le cri du phoque annelé prend principalement la forme d’aboiements, tandis que le printemps, il prend la forme de glapissements. Les gémissements du phoque barbu s’intensifient au printemps. Le cri des phoques à bandes n’a été capté qu’à l’automne 2008, pendant la période des eaux libres. Le répertoire des vocalisations connues du phoque à bandes a été élargi pour inclure trois autres cris, bien que deux séquences de cris stéréotypées étaient courantes. L’analyse rétrospective des enregistrements de cris de phoques annelés de 1982 et de phoques à bandes de 1967 a laissé entrevoir une grande stabilité du point de vue du répertoire des cris, et ce, sur de vastes échelles spatiales et temporelles

A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer’s disease and agitated behaviours: the HTA-SYMBAD trial

Background Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics. Objectives To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia. Design Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued). Setting Twenty-six UK secondary care centres. Participants Eligibility: probable or possible Alzheimer’s disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45. Interventions Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo. Outcome measures Primary: Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. Main economic outcome evaluation: incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months. Randomisation and blinding Participants allocated 1 : 1 : 1 ratio (to discontinuation of the carbamazepine arm, 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation. Results Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. Mean difference placebo-mirtazapine (−1.74, 95% confidence interval −7.17 to 3.69; p = 0.53). Harms: The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (n = 7) by week 16 than in the control group (n = 1). Post hoc analysis suggests this was of marginal statistical significance (p = 0.065); this difference did not persist at 6- and 12-month assessments. At 12 weeks, the costs of unpaid care by the dyadic carer were significantly higher in the mirtazapine than placebo group [difference: £1120 (95% confidence interval £56 to £2184)]. In the cost-effectiveness analyses, mean raw and adjusted outcome scores and costs of the complete cases samples showed no differences between groups. Limitations Our study has four important potential limitations: (1) we dropped the proposed carbamazepine group; (2) the trial was not powered to investigate a mortality difference between the groups; (3) recruitment beyond February 2020, was constrained by the COVID-19 pandemic; and (4) generalisability is limited by recruitment of participants from old-age psychiatry services and care homes. Conclusions The data suggest mirtazapine is not clinically or cost-effective (compared to placebo) for agitation in dementia. There is little reason to recommend mirtazapine for people with dementia with agitation. Future work Effective and cost-effective management strategies for agitation in dementia are needed where non-pharmacological approaches are unsuccessful. Study registration This trial is registered as ISRCTN17411897/NCT03031184. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 23. See the NIHR Journals Library website for further project information. Plain language summary It is common for people with Alzheimer’s disease to experience agitation, for example feeling restless or unsettled. If left untreated, agitation can lead to poorer quality of life and increased hospitalisation and strain for family carers. Often these symptoms are treated with medications that are usually used to manage psychosis (antipsychotic drugs), but such medication has limited effectiveness and can cause serious adverse effects to patients, including risk of increased death. Two medications that are already commonly prescribed for other health issues, mirtazapine (an antidepressant) and carbamazepine (a drug used to treat epilepsy), had been identified as a possible alternative way of treating agitation in Alzheimer’s disease that might not have the harms associated with antipsychotic medication. In this study, we compared the effects of giving mirtazapine or carbamazepine with a dummy drug (placebo) in people with Alzheimer’s disease who were experiencing agitation. The results of the study showed that neither medication was any more effective than the placebo in reducing agitation over 12 weeks in terms of improving symptoms, or in economic terms. Mirtazapine may lead to additional carer costs as compared to placebo. The study findings are stronger for mirtazapine than carbamazepine because the carbamazepine arm was stopped when it had recruited less than half the numbers needed. That was done because the study was not recruiting quickly enough to support both the mirtazapine and the carbamazepine arms. The findings from this study show that mirtazapine should not be recommended to treat agitation in Alzheimer’s disease. More work is needed to formulate effective ways and to test new drug and non-drug treatments for agitation in dementia. Scientific summary Background Agitation is common in people with dementia and impacts negatively on the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed efficacy and safety of mirtazapine (an antidepressant) and carbamazepine (an anticonvulsant) prescribed for agitation in dementia. Aim To assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in the treatment of agitation in dementia. Primary objectives To determine if mirtazapine is more clinically effective in reducing agitated behaviours in dementia than placebo, measured by Cohen-Mansfield Agitation Inventory (CMAI) score 12 weeks post randomisation. To determine if carbamazepine is more clinically effective in reducing agitated behaviours in dementia than placebo measured by CMAI score 12 weeks post randomisation. Methods Design Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine and carbamazepine over 12 weeks. Intervention (1) Mirtazapine, (2) carbamazepine and (3) placebo. Target dose: 45 mg of mirtazapine or 300 mg of carbamazepine. Inclusion and exclusion criteria Patients were eligible if the following criteria were met: a clinical diagnosis of probable or possible Alzheimer’s disease a diagnosis of co-existing agitated behaviours evidence that the agitated behaviours have not responded to management an assessment of CMAI (Long Form) score of 45 or greater written informed consent to enter and be randomised into the trial availability of a suitable informant. Exclusion criteria included: current treatment with antidepressants [including Monoamine Oxidase Inhibitors (MAOIs)], anticonvulsants or antipsychotics contraindications to the administration of mirtazapine or carbamazepine patients with second-degree atrioventricular block patients with a history of bone marrow depression or history of hepatic porphyrias cases too critical for randomisation (i.e. where there is a suicide risk or where the patient presents a risk of harm to others) female subjects under the age of 55 years of childbearing potential. Setting Participants were drawn from existing patients and new patient referrals to old age psychiatric services, memory clinics, specific Participant Identification Centres, primary care centres and those in care homes in 26 UK sites. Consent Capacity to consent was assessed before proceeding with the consent process and included consideration of the provision of assent by the patient and consent on their behalf by their legal representative. If the patient had capacity to consent, the carer consented to the provision of information on data for measures on the patient (e.g. CMAI) and also on themselves in terms of impact. Randomisation and blinding Participants were allocated in a 1 : 1 : 1 ratio (up to the discontinuation of the carbamazepine arm and 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, together with treatment as usual. Random allocation was block stratified by centre and type of residence (care home vs. own household) with random block lengths of three or six up to the discontinuation of the carbamazepine arm and thereafter of two or four. The trial was double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, the trial management team and the research workers who did baseline and follow-up assessments were masked to group allocation. Outcomes Primary outcome CMAI score (Long Form) at 12 weeks. Secondary outcomes Costs derived from Client Service Receipt Inventory, and quality-adjusted life-years from cost data alongside supplemented information from Dementia-Specific Quality of Life and EuroQol-5 Dimensions, five-level version interviews 12 weeks post randomisation. CMAI score and cost at 6 weeks post randomisation. Patient and carer quality of life, and carer outcomes at 6 and 12 weeks post randomisation. Adverse events from week 0 to week 16 and adherence at 6 and 12 weeks post randomisation. CMAI score, adverse events and adherence at 6 and 12 weeks, conditional on evidence of effectiveness of Investigational Medicinal Product over placebo. Longer-term follow-up: CMAI score, institutionalisation, death and clinical management at 26 and 52 weeks post randomisation. Sample size and statistical analysis An initial calculated sample size of 400 (randomised 1 : 1 : 1) provided 90% power using two-sided 5% significance tests to detect a drug versus placebo mean difference in CMAI score at 12 weeks of 6 points. This equated to an effect size of d = 0.4 (assuming a common standard deviation of 15) or a clinically significant 30% decrease in CMAI from placebo to active drug. With a realistic 15% attrition, a sample of 471 (157 per arm) was aimed for. Mid-trial, with the discontinuation of the carbamazepine arm, the sample size calculation was revisited with emerging data and it was adjusted so that the aim (excluding those randomised to carbamazepine) was for an overall sample of 222 (randomised 1 : 1) to provide 80% power using two-sided 5% significance tests to detect a mirtazapine versus placebo mean difference in CMAI score at 12 weeks of six points, assuming attrition of no more than 10%. Analyses were based on intention-to-treat (all participants were analysed according to the group to which they were randomised, irrespective of the treatment or dose received). The primary outcome (CMAI at 12 weeks) was analysed using a general linear regression model including baseline CMAI score as a covariate. General linear regression models were created for secondary outcomes. Economic evaluation The primary outcome for the economic evaluation was the incremental cost per six-point difference in CMAI score at 12 weeks, from a health and social care system perspective. Patient and public involvement Ensuring the involvement of people living with dementia and their family carers was integral to the Study of Mirtazapine for Agitated Behaviours in Dementia (SYMBAD) trial from the application for funding and trial design stage through to its conduct, analysis and communication. SN was a co-applicant and led on public/carer involvement in the trial throughout, and she was supported by a Lived Experience Advisory Panel (LEAP) group hosted by Sussex Partnership Foundation Trust (SPFT) co-ordinated by JF and the NIHR DeNDRoN (Dementias and Neurodegenerative Diseases Research Network) group. Protocol change Due to slower than expected recruitment the carbamazepine arm was discontinued in August 2018 when 40 people had been randomised to it. This summary therefore focusses on the mirtazapine versus placebo comparisons. Results Between January 2017 and February 2020, 204 participants were recruited and randomised to either the mirtazapine (n = 102) or placebo arm (n = 102). Mean CMAI scores at 12 weeks were not significantly different between participants allocated to receive mirtazapine and placebo [adjusted mean difference −1.74, 95% confidence interval (CI) −7.17 to 3.69; p = 0.53, direction of change in favour of mirtazapine but not statistically significant]. The number of controls with adverse events [65/102 (64%)] was similar to that in the mirtazapine group [67/102 (66%)]. There were more deaths in the mirtazapine group (n = 7) by week 16 than in the control group (n = 1), with post hoc analysis suggesting this was of marginal statistical significance (p = 0.065), but this difference did not persist at 6- and 12-month follow-ups. The cost-effectiveness analyses similarly showed no evidence of benefit of mirtazapine over placebo, and no difference in costs between groups at 12 weeks. The carbamazepine arm closed in August 2018 when there had been 40 randomisations to that group, we therefore do not have statistical power for comparisons with placebo. However, exploratory analyses using the same modelling as for mirtazapine versus placebo showed there was also little evidence of any benefits compared to placebo (adjusted mean difference 2.46, 95% CI −5.01 to 9.93; p = 0.52), with similar levels of adverse events reported [27/40 (68%)]. Conclusions This is a trial with negative findings but important clinical implications. The data suggest that mirtazapine is not clinically effective or cost-effective (compared to placebo) for clinically significant agitation in dementia. Our findings suggest that there is little reason to recommend the use of mirtazapine for people with dementia who experience agitation. Effective and cost-effective management strategies for agitation in dementia are needed, particularly where non-pharmacological approaches have been unsuccessful, and for people with dementia and their carers living in community settings. Trial registration This trial is registered as ISRCTN17411897 and ClinicalTrials.gov as NCT03031184. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment, Vol. 27, No. 23. See the NIHR Journals Library website for further project information

Toward a 21st-century health care system: Recommendations for health care reform

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges

SupPoRtive Exercise Programmes for Accelerating REcovery after major ABdominal Cancer surgery trial (PREPARE-ABC): pilot phase of a multicentre randomised controlled trial

Aim: PREPARE-ABC is a pragmatic multicentre randomised controlled trial including an internal pilot designed to assess the clinical and cost-effectiveness of pre- and postoperative exercise in relation to short- and longer-term postoperative recovery outcomes in colorectal cancer patients undergoing surgical resection. Here, we report on internal pilot phase data for the first 200 patients randomised to the trial, which included prespecified stop-go criteria used to inform the decision to progress to the fully powered trial by the funder. Methods: Eligible and consenting patients are randomly assigned (1:1:1) to hospital-supervised exercise, home-supported exercise or treatment as usual (TAU). Randomisation is concealed but clinical teams providing treatment and participants are unmasked. Primary outcomes are 30-day morbidity (Clavien-Dindo) and 12-month health-related quality of life (Medical Outcomes Study Health Questionnaire). Here, we present findings from the prespecified pilot phase which assessed feasibility of site set up, recruitment, adherence and acceptability of trial processes to patients and site staff. Results: Between 9 November 2016 and 18 May 2018, 18 sites were set up, with 200 patients randomised to either hospital-supervised exercise (68), home-supported exercise (69) or treatment as usual (TAU) (63). Across the groups, 19 patients did not proceed to surgery or withdrew and 52% experienced a complication. Over half of the participants (57%) in the hospital-supervised group attended ≥6 preoperative sessions and 50% attended ≥5 monthly postoperative exercise “booster sessions”. In the home-supported group, 70% patients engaged with ≥2 telephone support sessions in the preoperative phase and 80% engaged in ≥5 monthly telephone support “booster sessions”. Adverse events were reported by 22 patients and three patients reported a serious adverse event. The majority of complications were Clavien-Dindo grades 1–2; however, 16 patients experienced one or more Clavien-Dindo grade 3–4 complication(s). Conclusions: Results of the internal pilot phase confirm the feasibility of site set-up and patient recruitment, representativeness of the sample population and adequate adherence to hospital-supervised and home-supported exercise. On the basis of these positive results, progression to the fully-powered trial was authorised by the funder

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

Surface rupture of multiple crustal faults in the 2016 Mw 7.8 Kaikōura, New Zealand, earthquake

Multiple (>20 >20 ) crustal faults ruptured to the ground surface and seafloor in the 14 November 2016 M w Mw 7.8 Kaikōura earthquake, and many have been documented in detail, providing an opportunity to understand the factors controlling multifault ruptures, including the role of the subduction interface. We present a summary of the surface ruptures, as well as previous knowledge including paleoseismic data, and use these data and a 3D geological model to calculate cumulative geological moment magnitudes (M G w MwG ) and seismic moments for comparison with those from geophysical datasets. The earthquake ruptured faults with a wide range of orientations, sense of movement, slip rates, and recurrence intervals, and crossed a tectonic domain boundary, the Hope fault. The maximum net surface displacement was ∼12  m ∼12  m on the Kekerengu and the Papatea faults, and average displacements for the major faults were 0.7–1.5 m south of the Hope fault, and 5.5–6.4 m to the north. M G w MwG using two different methods are M G w MwG 7.7 +0.3 −0.2 7.7−0.2+0.3 and the seismic moment is 33%–67% of geophysical datasets. However, these are minimum values and a best estimate M G w MwG incorporating probable larger slip at depth, a 20 km seismogenic depth, and likely listric geometry is M G w MwG 7.8±0.2 7.8±0.2 , suggests ≤32% ≤32% of the moment may be attributed to slip on the subduction interface and/or a midcrustal detachment. Likely factors contributing to multifault rupture in the Kaikōura earthquake include (1) the presence of the subduction interface, (2) physical linkages between faults, (3) rupture of geologically immature faults in the south, and (4) inherited geological structure. The estimated recurrence interval for the Kaikōura earthquake is ≥5,000–10,000  yrs ≥5,000–10,000  yrs , and so it is a relatively rare event. Nevertheless, these findings support the need for continued advances in seismic hazard modeling to ensure that they incorporate multifault ruptures that cross tectonic domain boundaries