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Building on prior work using Tom Dishion's Family Check-Up, the current article examined intervention effects on dysregulated irritability in early childhood. Dysregulated irritability, defined as reactive and intense response to frustration, and prolonged angry mood, is an ideal marker of neurodevelopmental vulnerability to later psychopathology because it is a transdiagnostic indicator of decrements in self-regulation that are measurable in the first years of life that have lifelong implications for health and disease. This study is perhaps the first randomized trial to examine the direct effects of an evidence- and family-based intervention, the Family Check-Up (FCU), on irritability in early childhood and the effects of reductions in irritability on later risk of child internalizing and externalizing symptomatology. Data from the geographically and sociodemographically diverse multisite Early Steps randomized prevention trial were used. Path modeling revealed intervention effects on irritability at age 4, which predicted lower externalizing and internalizing symptoms at age 10.5. Results indicate that family-based programs initiated in early childhood can reduce early childhood irritability and later risk for psychopathology. This holds promise for earlier identification and prevention approaches that target transdiagnostic pathways. Implications for future basic and prevention research are discussed.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
The aim of the present study is to use the syndemic framework to investigate the risk of contracting HIV in the US population. Cross-sectional analyses are from The National Health and Nutrition Examination Survey. We extracted and aggregated data on HIV antibody test, socio-demographic characteristics, alcohol use, drug use, depression, sexual behaviours and sexually transmitted diseases from cycle 2009–2010 to 2015–2016. We carried out weighted regression among young adults (20–39 years) and adults (40–59 years) separately. In total, 5230 men and 5794 women aged 20–59 years were included in the present analyses. In total, 0.8% men and 0.2% women were tested HIV-positive. Each increasing HIV risk behaviour was associated with elevated odds of being tested HIV-positive (1.15, 95% CI 1.15–1.15) among young adults and adults (1.61, 95% CI 1.61–1.61). Multi-faceted, community-based interventions are urgently required to reduce the incidence of HIV in the USA.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Prevented planting provision in crop insurance protects producers from failure to plant attributable to natural causes. We determined the impact of this provision at various crop insurance coverage levels on prevented planting claims and ex post moral hazard. The moral hazard incentive in the prevented planting provision is stronger for corn than soybeans. Reducing the prevented planting coverage factor for corn could likely reduce moral hazard, but the degree of the reduction will likely depend on the revenue protection coverage level. Conversely, we found moral hazard is unlikely to occur for soybean production regardless of the revenue protection coverage level.
Solvency II came into force on 1 January 2016 and included a transitional measure on technical provisions (“TMTP”) designed to help smooth in the capital impact of Solvency II over a 16-year period. The working party’s view is that the main intention of the TMTP is to mitigate the impact of the introduction of the risk margin, which significantly increases the technical provisions of firms, relative to their Solvency I Pillar 2 liabilities.
The majority of firms who hold a TMTP have now had at least one recalculation approved by the Prudential Regulation Authority (PRA); or are in the process of applying for a recalculation. Despite this large number of approved recalculations, there remains significant uncertainty in the industry around the approach and triggers for recalculation.
This paper considers aspects of TMTP recalculation for regulated UK life firms, for example practicalities of the calculation, asset and liability considerations, and communications/announcements.
In this paper, we outline the need for pragmatism when considering the approach to recalculation of a measure originally intended to serve as the bridge between two regimes. We call for an allowance for doing what is sensible in a principles-based regime balancing what might be more theoretically correct with what is practical and possible to support effective management of the business.
In this work, we study the effect of the compression-corner angle on the streamwise turbulent kinetic energy (sTKE) and structure in Mach 2.8 flow. Krypton tagging velocimetry (KTV) is used to investigate the incoming turbulent boundary layer and flow over
compression corners. The experiments were performed in a 99 %
and 1 % Kr gas mixture in the Arnold Engineering Development Complex (AEDC) Mach 3 Calibration Tunnel (M3CT) at
. A figure of merit is defined as the wall-normal integrated sTKE (
), which is designed to identify turbulence amplification by accounting for the root-mean-squared (r.m.s.) velocity fluctuations and shear-layer width for the different geometries. We observe that the
increases as an exponential with the compression-corner angle near the root when normalized by the boundary-layer value. Additionally, snapshot proper orthogonal decomposition (POD) is applied to the KTV results to investigate the structure of the flow. From the POD results, we extract the dominant flow structures and compare each case by presenting mean-velocity maps that correspond to the largest positive and negative POD mode coefficients. Finally, the POD spectrum reveals an inertial range common to the boundary-layer and each compression-corner flow that is present after the first
dominant POD modes.
This study investigated the characteristics of subjective memory complaints (SMCs) and their association with current and future cognitive functions.
A cohort of 209 community-dwelling individuals without dementia aged 47–90 years old was recruited for this 3-year study. Participants underwent neuropsychological and clinical assessments annually. Participants were divided into SMCs and non-memory complainers (NMCs) using a single question at baseline and a memory complaints questionnaire following baseline, to evaluate differential patterns of complaints. In addition, comprehensive assessment of memory complaints was undertaken to evaluate whether severity and consistency of complaints differentially predicted cognitive function.
SMC and NMC individuals were significantly different on various features of SMCs. Greater overall severity (but not consistency) of complaints was significantly associated with current and future cognitive functioning.
SMC individuals present distinctive features of memory complaints as compared to NMCs. Further, the severity of complaints was a significant predictor of future cognition. However, SMC did not significantly predict change over time in this sample. These findings warrant further research into the specific features of SMCs that may portend subsequent neuropathological and cognitive changes when screening individuals at increased future risk of dementia.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Introduction: The effectiveness of intravenous alteplase is highly time dependent, and very short door-to-needle times (DNT) of 30 minutes or less have been reported in single centre hospitals, but never in an entire population. QuICR (Quality Improvement and Clinical Research) Alberta Stroke Program aimed to reduce DNT to a median of 30 minutes across the Canadian province of Alberta. Methods: We used the Improvement Collaborative Methodology from early 2015 to September 2016 with participation from all 17 Stroke Centres in Alberta. This methodology included 4 face-to-face workshops, site visits, webinars, data collection, data feedback, intensive process mapping, and process improvements. We compared data in the pre-intervention period from 2009-2014 (collected during the Alberta Provincial Stroke Strategy) to data in the post-intervention period from March 2016-February 2017 (collected during the QuICR DTN Collaborative). Data from January 2015-February 2016 were excluded, as improvements were being implemented during this time. Results: There were a total of 2,322 treated cases in the pre- and post-intervention periods. The results show that the median DNT dropped from 68 minutes (n=1846) in the pre-intervention period to 36 minutes (n=476) in the post-intervention period (p<0.001). There were reductions in DNT across all hospital types: median DNT dropped from 63 to 32 minutes in Urban Tertiary Centres (p<0.001), from 73 to 32 minutes in Community with 24/7 neurology (p<0.001), from 85 to 62 minutes in Community with limited/no neurology (p<0.001), and from 74 to 52.5 minutes in rural centres (p<0.001). Conclusion: There were 21.5 to 41 minute reductions in median DNT across all hospital types including smaller rural and community hospitals. A targeted multi-site improvement collaborative can be an effective intervention to reduce DNT across an entire population.
Introduction: Checklists used during intubation have been associated with improved patient safety. Since simulation provides an effective and safe learning environment, it is an ideal modality for training practitioners to effectively employ an airway checklist. However, physician attitudes surrounding the utility of both checklists and simulation may impede the implementation process of airway checklists into clinical practice. This study sought to characterize attitudinal factors that may impact the implementation of airway checklists, including perceptions of checklist utility and simulation training. Methods: Emergency medicine (EM) residents and physicians working more than 20 hours/month in an emergency department from two academic centres were invited to participate in a simulated, randomized controlled trial (RCT) featuring three scenarios performed with or without the use of an airway checklist. Following participation in the scenarios, participants completed either a 26-item (control group), or 35-item (checklist group) paper-based survey comprised of multiple-choice, Likert-type, rank-list and open-ended questions exploring their perceptions of the airway checklist (checklist group only) and simulation as a learning modality (all participants). Results: Fifty-four EM practitioners completed the questionnaire. Most control group participants (n=24/25, 96.0%) believed an airway checklist would have been helpful (scored 5/7 or greater) for the scenarios. The majority of checklist group participants (n=29) believed that the checklist was helpful for equipment (27, 93.1%) and patient (26, 89.6%) preparation, and post-intubation care (21, 82.8%), but that the checklist delayed definitive airway management and was not helpful for airway assessment, medication selection, or choosing to perform a surgical airway. This group also believed that using the airway checklist would reduce errors during intubation (27, 93.1%) and that the simulated scenarios were beneficial for adopting the use of the checklist (28, 96.6%). Fifty-three participants (98.1%) believed that simulation is beneficial for continuing medical education and 51 respondents (94.4%) thought that skills learned in this simulation were transferable. Conclusion: EM practitioners participating in a simulation-based RCT of an airway checklist had positive attitudes towards both the utility of airway checklists and simulation as a learning modality. Thus, simulation may be an effective process to train practitioners to use airway checklists prior to clinical implementation.
Introduction: One of the most high-risk tasks regularly performed by emergency medicine (EM) physicians is airway management. Many studies identify an increase in adverse events associated with airway management outside of the operating theatre. Errors of omission are the single most common human error type. To address this risk, the checklist is becoming a common pre-intubation tool. Simulation is a safe setting in which to study the implementation of a new airway checklist. The purpose of this study was to determine if a novel airway checklist decreases practitioners rates of omission of important tasks during simulated resuscitation scenarios. Methods: This was a dual-centre, randomized controlled trial of a novel airway checklist utilized by EM practitioners in a simulated environment. The 29-item peri-intubation checklist was derived by experienced EM practitioners following a review of airway checklists in published and gray literature. Participants were EM residents or EM physicians who work more than 20 hours/month in an emergency department. Volunteers were recruited from two academic health centres to complete three simulated scenarios (two requiring intubation, one cricothyroidotomy), and were randomized to either regular care or checklist use. A minimum of two assessors documented the number of omitted tasks deemed important in airway management and the time until definitive airway management. Discrepancies between assessors were resolved by single-assessor video review. Results: Fifty-four EM practitioners participated. There was no significant difference in baseline characteristics between the two study groups. The average percentage of omitted tasks over the three scenarios was 45.7% in the control group (n=25) and 13.5% in the checklist group (n=29) an absolute difference of 32.2% (95% CI: 27.8%, 36.6%). Time to intubation (normally distributed) was significantly longer in the checklist group for the first two scenarios (mean difference 114.10s, 95% CI: 48.21s, 179.98s and 76.34s, 95% CI:31.35s ,121.33s), but there was no statistical difference in the third scenario where cricothyroidotomy was required (mean difference 33.75s, 95% CI: -28.14s, 95.65s). Conclusion: In a simulated setting, use of an airway checklist significantly decreased the omission rate of important airway management tasks, however it increased the time to definitive airway management. Further study is required to determine if these findings are consistent in a clinical setting and how they impact the rate of adverse events.
A review of physiology and behaviour–based studies on the function of stereotypic behaviour indicates contradiction and inconsistency within the literature. By considering appropriate neurochemical data alongside an existing model of motivation (Hughes and Duncan, 1988), a greater understanding of the function of stereotypy may be gained. The Hughes and Duncan model (1988), described stereotypies as highly motivated appetitive behaviours performed repeatedly in an environment where consummatory goals are denied. Moreover, appetitive behaviours activate reward circuitry such as the ventral tegmental area and nucleus accumbens and are thus considered to have a reward value associated with their performance (Carr, 2002; Jones et al., 1990). Stress induced sensitisation of reward circuitry may result in appetitive ‘stereotypies’ having increased reward value, perhaps becoming consummatory in their own right. In such a scenario, stereotypic behaviour could function as a coping tool, allowing the animal to counter the effects of an aversive environment.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
The mainstay of management of epistaxis refractory to first aid and cautery is intranasal packing. This review aimed to identify evidence surrounding nasal pack use.
A systematic review of the literature was performed using standardised methodology.
Twenty-seven eligible articles were identified relating to non-dissolvable packs and nine to dissolvable packs. Nasal packing appears to be more effective when applied by trained professionals. For non-dissolvable packs, the re-bleed rates for Rapid Rhino and Merocel were similar, but were higher with bismuth iodoform paraffin paste packing. Rapid Rhino packs were the most tolerated non-dissolvable packs. Evidence indicates that 96 per cent of re-bleeding occurs within the first 4 hours after nasal pack removal. Limited evidence suggests that dissolvable packs are effective and well tolerated by patients. There was a lack of evidence relating to: the duration of pack use, the economic effects of pack choice and the appropriate care setting for non-dissolvable packs.
Rapid Rhino packs are the best tolerated, with efficacy equivalent to nasal tampons. FloSeal is easy to use, causes less discomfort and may be superior to Merocel in anterior epistaxis cases. There is no strong evidence to support prophylactic antibiotic use.
The Murchison Widefield Array (MWA), located in Western Australia, is one of the low-frequency precursors of the international Square Kilometre Array (SKA) project. In addition to pursuing its own ambitious science programme, it is also a testbed for wide range of future SKA activities ranging from hardware, software to data analysis. The key science programmes for the MWA and SKA require very high dynamic ranges, which challenges calibration and imaging systems. Correct calibration of the instrument and accurate measurements of source flux densities and polarisations require precise characterisation of the telescope’s primary beam. Recent results from the MWA GaLactic Extragalactic All-sky Murchison Widefield Array (GLEAM) survey show that the previously implemented Average Embedded Element (AEE) model still leaves residual polarisations errors of up to 10–20% in Stokes Q. We present a new simulation-based Full Embedded Element (FEE) model which is the most rigorous realisation yet of the MWA’s primary beam model. It enables efficient calculation of the MWA beam response in arbitrary directions without necessity of spatial interpolation. In the new model, every dipole in the MWA tile (4 × 4 bow-tie dipoles) is simulated separately, taking into account all mutual coupling, ground screen, and soil effects, and therefore accounts for the different properties of the individual dipoles within a tile. We have applied the FEE beam model to GLEAM observations at 200–231 MHz and used false Stokes parameter leakage as a metric to compare the models. We have determined that the FEE model reduced the magnitude and declination-dependent behaviour of false polarisation in Stokes Q and V while retaining low levels of false polarisation in Stokes U.
Yeasts are the first micro-organism that become active in the silage upon exposure to air, using the residual sugars and lactic acid to produce carbon dioxide. Maize silage is particularly prone to spoilage as maize silage tends to have a larger concentration of water soluble carbohydrates, which was considered to be a better substrate for micro-organisms than volatile fatty acids (Auerbach et al., 1998). The aim of this experiment was to measure the effect of inoculating maize silage with Maize-all GS (inoculant) and Sil-all Fireguard (inoculant and preservative) on aerobic stability.
IR spectroscopy in the range 12–230 μm with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA’s large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z ~ 6.