Touchstones of Equivalence and the Houdini Transformation.

Inspired by Peter Molenaar's Houdini transformation, we consider the idea of touchstones between different models. Touchstones represent instances where models that appear different on the surface can have equivalent characteristics. Touchstones can appear as identical tests of model parameters. They can exist in the mean structure, in the covariance structure, or in both. In the latter case, the models will generate identical mean and covariance structures and will fit the data equally well. After showing some examples of touchstones and how they result from constraints on a general model, we show how that idea can suggest Molenaar's Houdini transformation. This transformation allows one to take a latent variable model and derive an equivalent model comprised solely of manifest (observed) variables. As equivalent models, the parameters of one can be transformed into the parameters of the other.

Farmers Views on the Implementation of On-Farm Emergency Slaughter for the Management of Acutely Injured Cattle in Ireland.

Four management options for acutely injured cattle in Ireland exist: treatment, unless cattle are severely injured; on-farm emergency slaughter (OFES); casualty slaughter (CS) if the animal is certified fit for transport; or euthanasia. OFES is designed to prevent transport of welfare-compromised cattle. An online survey of farmers in Ireland was carried out between April and July 2021 and focused on events during 2020. A theoretical framework of capacity, willingness, and opportunity was used to explore farmers' perceptions. Responses from 94 farmers (49 dairy and 45 beef) were analysed; not all respondents answered all questions. Respondents indicated that the incidence of acutely injured cattle in Ireland is low. A majority reported not having an acutely injured animal for greater than 36 months. Most respondents had a positive attitude towards OFES for animal welfare reasons and were aware of relevant regulations and guidelines. Barriers to OFES included a lack of availability of OFES, and dairy farmers indicated that it had a similar financial impact as euthanasia. A parallel study with veterinarians indicated a higher incidence of acutely injured cattle in Ireland; the current results may be due to the demographic or the sensitivity of the topic. Nationwide electronic data capture on the cause of mortality could support improvements in the management of acutely injured cattle and enable surveillance of the proportion of these cattle undergoing OFES, euthanasia, or CS.

Management of acutely injured cattle by on farm emergency slaughter: Survey of veterinarian views.

Background: Fitness to transport is a key provision in animal welfare regulations in the European Union, and for the management of acutely injured cattle. Whilst treatment may be appropriate for some injuries, three common production outcomes for acutely injured cattle are; on farm emergency slaughter (OFES), casualty slaughter (CS) or euthanasia. The aims of this study were to evaluate the perceptions of veterinarians, working in Ireland, on the use of OFES for the management of acutely injured cattle and to evaluate the influence of capacity, willingness and opportunity on their ability to operate OFES. Methodology: Two online surveys of veterinarians working in Ireland, Private Veterinary Practitioners (PVPs) and Official Veterinarians (OVs), were conducted through QualtricsXM over a 7-week period between April and June of 2021. Quantitative and qualitative questions were developed and analyzed using the tripartite framework of capacity, willingness, and opportunity to collect relevant data about the management of acutely injured cattle and the provision of OFES in Ireland by veterinarians. Results: 43 OVs and 85 PVPs participated in the survey. OVs regulated on average 4.2 abattoirs, of which 21.6% accepted OFES. Participants reported 343 and 377 OFES and CS, respectively, in 2020. 62.4% PVPs had not certified cattle for OFES, or CS. Limb fracture accounted for 79% OFES, 34.5% CS and 47.9% euthanized acutely injured cattle. 63.3% OVs and 44% PVPs were not aware of abattoirs providing OFES within 100 km of their workplace. Lack of availability of OFES negatively associated with PVP knowledge of the procedure. Regulations and guidelines were the most common source of information on OFES for PVPs. Conclusion: Increasing the availability of OFES may help to improve the management of acutely injured cattle, especially those with limb fractures that are unfit for transport.

Development and initial validation of the Spanish form of the adjustment scales for preschool intervention (ASPI).

The purpose of the study was to develop and validate a Spanish language form of the Adjustment Scales for Preschool Intervention (ASPI) for use by early childhood teachers. A multi-step, mixed method adaptation and translation process of the English form was used to increase the cultural relevance, linguistic comparability, and metric equivalence of the measure in its Spanish language form. Exploratory and confirmatory factor analyses in a diverse sample of preschool children from low-income families (N = 4077) revealed two higher order behavioral dimensions of Overactivity and Underactivity. ASPI dimension scores across Spanish and English language forms were horizontally equated through IRT. Criterion-related validity using multilevel models was established through concurrent associations with social, emotional, behavioral, and academic readiness skills. Policy and practice applications, and future directions for the use of scale scores are discussed.

Confirming the Presence of Legionella pneumophila in Your Water System: A Review of Current Legionella Testing Methods.

Legionnaires' disease has been recognized since 1976 and Legionella pneumophila still accounts for more than 95% of cases. Approaches in countries, including France, suggest that focusing risk reduction specifically on L. pneumophila is an effective strategy, as detecting L. pneumophila has advantages over targeting multiple species of Legionella. In terms of assays, the historically accepted plate culture method takes 10 days for confirmed Legionella spp. results, has variabilities which affect trending and comparisons, requires highly trained personnel to identify colonies on a plate in specialist laboratories, and does not recover viable-but-non-culturable bacteria. PCR is sensitive, specific, provides results in less than 24 h, and determines the presence/absence of Legionella spp. and/or L. pneumophila DNA. Whilst specialist personnel and laboratories are generally required, there are now on-site PCR options, but there is no agreement on comparing genome units to colony forming units and action limits. Immunomagnetic separation assays are culture-independent, detect multiple Legionella species, and results are available in 24 h, with automated processing options. Field-use lateral flow devices provide presence/absence determination of L. pneumophila serogroup 1 where sufficient cells are present, but testing potable waters is problematic. Liquid culture most probable number (MPN) assays provide confirmed L. pneumophila results in 7 days that are equivalent to or exceed plate culture, are robust and reproducible, and can be performed in a variety of laboratory settings. MPN isolates can be obtained for epidemiological investigations. This accessible, non-technical review will be of particular interest to building owners, operators, risk managers, and water safety groups and will enable them to make informed decisions to reduce the risk of L. pneumophila.

On Farm Emergency Slaughter and Emergency Killing of Acutely Injured Cattle: Analysis of Guidelines From Five Jurisdictions.

BACKGROUND: In July 2009, the Farm Animal Welfare Advisory Council (FAWAC) in the Republic of Ireland published Animal Welfare Guidelines for the Management of Acutely Injured Animals on Farm in support of a new Irish regulation designed to permit on-farm emergency slaughter (OFES) of cattle. The purpose of this study was to evaluate the FAWAC guidelines, to determine if they remain fit for purpose by comparing them with five guidelines on the management of acutely injured cattle from four jurisdictions purposively selected because of their relevance to OFES, and to represent geographical and organisational diversity; The United Kingdom, Australia, New Zealand and British Columbia/Canada. METHODOLOGY: Content and Thematic Analysis were used to compare the incidence and frequency of themes in the six guidelines using NVIVO 12. RESULTS: Humane killing and slaughter of animals and the prevention of unnecessary suffering at time of killing were emphasised in all guidelines. Thematic Analysis identified seven primary themes ("parent nodes"): animal welfare; decision tree; certification; legislation; stakeholders; transport and; veterinary ethics. Parent nodes encompassed 26 secondary themes ("child nodes") including casualty slaughter, on-farm emergency slaughter, euthanasia, unnecessary suffering, animal owner, private veterinary practitioner, official veterinarian and fitness for transport. Guidelines outlined stakeholders' roles in relation to all aspects of managing acutely injured cattle. Results showed similarities between FAWAC, the British Cattle Veterinary Association and the British Columbian/Canadian guidelines in relation to OFES as a method to address acutely injured cattle. OFES is not allowed in Australia or New Zealand as a method of managing acutely injured cattle. CONCLUSIONS: Animal welfare guidelines play a pivotal role in informing all stakeholders involved in the management of acutely injured cattle. Guidelines vary from prescriptive standard operating procedures on actions that should be undertaken for food safety reasons, to descriptive guidance upholding practicalities in relation to equipment and methods to be used in managing acutely injured cattle not meant for human consumption. The FAWAC guidelines remain substantially relevant today and consistent with other welfare guidelines published in the jurisdictions that formed part of the study. However, they need to be reviewed to align with current regulations.

Legionella risk in evaporative cooling systems and underlying causes of associated breaches in health and safety compliance.

Legionella bacteria can colonise and proliferate in water systems in the built environment and can be spread by aerosol generation. If inhaled by a susceptible individual, this can lead to respiratory infections such as Legionnaires' Disease (LD), or the generally milder Pontiac fever. Evaporative cooling systems (ECS), including cooling towers, used in industrial processes to dissipate excessive heat are prone to contamination by Legionella. From these systems it is possible for contaminated aerosols to be dispersed over a wide area, potentially exposing workers on site, neighbouring workplaces or nearby members of the public. Analysis of reported data on outbreaks of LD in Great Britain, collated for a ten year period, identified 44 separate legionellosis outbreaks of which seven were attributed to ECS and were responsible for 229 infections and 10 fatalities. This prompted an examination of health and safety inspection records which revealed, over a five year period, 321 enforcement actions taken against failings in Legionella control, of which 31% were attributed to cooling towers. Based on this evidence, an intervention programme was undertaken by health and safety inspectors in which 1,906 sites with ECS were inspected. During these inspections, sites were rated against four topics that are used to demonstrate compliance with statutory requirements for Legionella control: Risk Assessment; Written Control Scheme; Implementation of Control Scheme; and Record Keeping. While there was compliance at the majority of sites, breaches of the legislation were found at 625 sites (33% of those inspected), leading to 409 Improvement Notices (compelling dutyholders to make improvements to health and safety breaches of law in a given timeframe) and 12 Prohibition Notices (compelling dutyholders to stop work until they have remedied breaches in health and safety law) being served at 229 sites (12.0% of those inspected). Data from the intervention programme was analysed to identify root causes of these breaches of legislation on Legionella control. The majority of Improvement Notices (53%) were issued for the 'lack of effective implementation of a Written Control Scheme', with 'Risk Assessment' and 'Written Control Scheme' both accounting for 23%. More detailed examination showed major problems to be lack of training; failure to maintain the cleanliness of cooling towers and the water within them; risk assessments either being absent or not up to date, i.e., no longer representing the risks present; and Written Control Schemes being absent or insufficiently detailed. This provides a valuable data resource for dutyholders, so that they can understand where they need to focus to achieve significant improvement in legal compliance and therefore reduce the risk of LD for employees and members of the public affected by their workplace, and valuable data for regulators to target future interventions aimed at improving dutyholder compliance leading to better protection of workers and members of the public.

Increased Weight Gain During the Long Interdialytic Period Is Associated with Minor Effects on Blood Pressure Control in Clinically Stable In-Centre Haemodialysis Patients.

BACKGROUND/AIMS: Three-day-a-week chronic haemodialysis (cHD) involves 1 long (72 h) and 2 short (48 h) inter-dialytic periods (IDPs). We aimed to determine whether BP control following the long IDP is inferior to the short IDPs. METHODS: All pre- and post-dialysis BP and weight measurements over a 4-week period were retrospectively analyzed among 135 clinically stable cHD patients at 2 academic centres with comparisons between measurements recorded following short and long IDPs. Subsequently, 23 clinically stable cHD patients underwent 24-h ambulatory blood pressure monitoring (ABPM) during the final day/night cycle of the long IDP and 1 short IDP within the same week. RESULTS: In combined and separate analyses of the 2 retrospective cohorts, pre-dialysis BP parameters were not different following long and short IDPs despite greater inter-dialytic weight gain (IDWG) during the long IDP. Subgroup analyses of the total cohort showed no evidence for inferior BP control during the long IDP among those with high %IDWG. In the ABPM study, nocturnal hypertension and loss of nocturnal dipping were frequent. Furthermore, daytime systolic blood pressure (SBP) and pulse pressure were modestly higher during the last day/night cycle of the long compared with short IDP. CONCLUSION: In stable cHD patients, the greater IDWG that occurred during the long IDP was not associated with overtly inferior BP control as reflected in pre-dialysis BP measurements. However, modestly higher daytime SBP was evident towards the end of the long IDP by 24 h ABPM. Thus, while fluid gain has well-documented associations with hypertension and adverse cardiovascular outcomes, the excess IDWG that occurs during the long IDP exerts relatively minor effects on BP control in patients on well-established dialysis regimens that are better identified by ambulatory monitoring.

Latent Growth Curve and Repeated Measures ANOVA Contrasts: What the Models are Telling You.

The relationship between the latent growth curve and repeated measures ANOVA models is often misunderstood. Although a number of investigators have looked into the similarities and differences among these models, a cursory reading of the literature can give the impression that they are very different models. Here we show that each model represents a set of contrasts on the occasion means. We demonstrate that the fixed effects parameters of the estimated basis vector latent growth curve model are merely a transformation of the repeated measures ANOVA fixed effects parameters. We further show that differences in fit in models that estimate the same means structure can be due to the different error covariance structures implied by the model. We show these relationships both algebraically and through using data from a simulation.

Latent national subpopulations of early education classroom disengagement of children from underresourced families.

This research examined the latent developmental patterns for early classroom disengagement among children from some of the most underresourced families in the nation. Based on standardized teacher observations from the Head Start Impact Study, a nationally representative sample of children (N=1377) was assessed for manifestations of reticent/withdrawn and low energy behavior over four years spanning prekindergarten through first grade. For each form of disengagement, latent growth mixture modeling revealed three distinct subpopulations of change patterns featuring a dominant class associated with generally good classroom adjustment, a medial class that varied close to the population average over time, and a more extreme class (about 10% of the population) whose adjustment was relatively marginal and sometimes reached problematic levels. Whereas reticent/withdrawn behavior ordinarily subsided over time, low energy behavior increased. More extreme low energy behaviors tended to dissipate through schooling and extreme reticence/withdrawal became more accentuated, with both types associated with later academic and social problems. Attendant risk and protective factors are identified and mitigating assessment and prevention measures are discussed.

Engineering Bacillus megaterium for production of functional intracellular materials.

BACKGROUND: Over the last 10-15 years, a technology has been developed to engineer bacterial poly(3-hydroxybutyrate) (PHB) inclusions as functionalized beads, for applications such as vaccines, diagnostics and enzyme immobilization. This has been achieved by translational fusion of foreign proteins to the PHB synthase (PhaC). The respective fusion protein mediates self-assembly of PHB inclusions displaying the desired protein function. So far, beads have mainly been produced in recombinant Escherichia coli, which is problematic for some applications as the lipopolysaccharides (LPS) co-purified with such inclusions are toxic to humans and animals. RESULTS: In this study, we have bioengineered the formation of functional PHB inclusions in the Gram-positive bacterium Bacillus megaterium, an LPS-free and established industrial production host. As B. megaterium is a natural PHB producer, the PHB-negative strain PHA05 was used to avoid any background PHB production. Plasmid-mediated T7 promoter-driven expression of the genes encoding ß-ketothiolase (phaA), acetoacetyl-CoA-reductase (phaB) and PHB synthase (phaC) enabled PHB production in B. megaterium PHA05. To produce functionalized PHB inclusions, the N- and C-terminus of PhaC was fused to four and two IgG binding Z-domains from Staphylococcus aureus, respectively. The ZZ-domain PhaC fusion protein was strongly overproduced at the surface of the PHB inclusions and the corresponding isolated ZZ-domain displaying PHB beads were found to purify IgG with a binding capacity of 40-50 mg IgG/g beads. As B. megaterium has the ability to sporulate and respective endospores could co-purify with cellular inclusions, a sporulation negative production strain was generated by disrupting the spoIIE gene in PHA05. This strain did not produce spores when tested under sporulation inducing conditions and it was still able to synthesize ZZ-domain displaying PHB beads. CONCLUSIONS: This study provides proof of concept for the successful genetic engineering of B. megaterium as a host for the production of functionalized PHB beads. Disruption of the spoIIE gene rendered B. megaterium incapable of sporulation but particularly suitable for production of functionalized PHB beads. This sporulation-negative mutant represents an improved industrial production strain for biotechnological processes otherwise impaired by the possibility of endospore formation.

Increased expression of estrogen-related receptor ß during adaptation of adult cardiomyocytes to sustained hypoxia.

UNLABELLED: Estrogen-related Receptors (ERR) are members of the steroid hormone receptor superfamily of transcription factors that regulate expression of genes required for energy metabolism including mitochondrial biogenesis, fatty acid oxidation and oxidative phosphorylation. While ERRα and EPPγ isoforms are known to share a wide array of target genes in the adult myocardium, the function of ERRß has not been characterized in cardiomyocytes. The purpose of this study was to determine the role of ERRß in regulating energy metabolism in adult cardiomyocytes in primary culture. Adult feline cardiomyocytes were electrically stimulated to contract in either hypoxia (0.5% O2) or normoxia (21% O2). As compared to baseline values measured in normoxia, ERRß mRNA levels increased significantly after 8 hours of hypoxia and remained elevated over 24 h. Conversely, ERRß mRNA decreased to normoxic levels after 4 hours of reoxygenation. Hypoxia increased expression of the α and ß isoforms of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 (PGC-1) mRNA by 6-fold and 3-fold, respectively. Knockdown of ERRß expression via adenoviral-mediated delivery of ERRß shRNA blocked hypoxia-induced increases in PGC-1ß mRNA, but not PGC-1α mRNA. Loss of ERRß had no effect on mtDNA content as measured after 24 h of hypoxia. To determine whether loss of ERRß affected mitochondrial function, oxygen consumption rates (OCR) were measured in contracting versus quiescent cardiomyocytes in normoxia. OCR was significantly lower in contracting cardiomyocytes expressing ERRß shRNA than scrambled shRNA controls. Maximal OCR also was reduced by ERRß knockdown. IN CONCLUSION: 1) hypoxia increases in ERRß mRNA expression in contracting cardiomyocytes; 2) ERRß is required for induction of the PGC-1ß isoform in response to hypoxia; 3) ERRß expression is required to sustain OCR in normoxic conditions.

Transition and protective agency of early childhood learning behaviors as portents of later school attendance and adjustment.

This article reports on the study of differential change trajectories for early childhood learning behaviors as they relate to future classroom adjustment and school attendance. A large sample (N=2152) of Head Start children was followed through prekindergarten, kindergarten, and 1st grade. Classroom learning behaviors were assessed twice each year by teachers who observed gradual declines in Competence Motivation and Attentional Persistence as children transitioned through schooling. Cross-classified multilevel growth models revealed distinct transitional pathways for future adjustment versus maladjustment and sporadic versus chronic absenteeism. Generalized multilevel logistic modeling and receiver operating characteristic curve analyses showed that teachers' earliest assessments were substantially predictive of eventual good classroom adjustment and school attendance, with increasing accuracy for prediction of future sociobehavioral adjustment as time progressed.

Estrogen-Related Receptor α (ERRα) is required for adaptive increases in PGC-1 isoform expression during electrically stimulated contraction of adult cardiomyocytes in sustained hypoxic conditions.

BACKGROUND AND OBJECTIVES: In adult myocardium, Estrogen-Related Receptor α (ERRα) programs energetic capacity of cardiomyocytes by regulating expression of target genes required for mitochondrial biogenesis, fatty acid metabolism and oxidative phosphorylation. Transcriptional activation by ERRα is dependent on the α or ß isoform of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 (PGC-1). This study utilized a model of continuously contracting adult cardiomyocytes to determine the effects of sustained oxygen reduction (hypoxia) on ERRα target gene expression. METHODS AND RESULTS: Adult feline cardiomyocytes in primary culture were electrically stimulated to contract at 1 Hz in either normoxia (21% O2) or hypoxia (0.5% O2). Compared to normoxia, hypoxia increased PGC-1α mRNA and PGC-1ß mRNA levels by 16-fold and 14-fold after 24h. ERRα mRNA levels were increased 3-fold by hypoxia over the same time period. Treatment of cardiomyocytes with XCT-790, an ERRα inverse agonist, caused knockdown of ERRα protein expression. The increases in PGC-1 mRNA levels in response to hypoxia were blocked by XCT-790 treatment, which indicates that expression of PGC-1 isoforms is dependent on ERRα activity. The products of two ERRα target genes required for energy metabolism, Cox6c mRNA and Fabp3 mRNA, increased by 4.5-fold and 3.5 fold after 24h of hypoxia as compared to normoxic controls. These increases were blocked by XCT-790 treatment of hypoxic cardiomyocytes with a concomitant decrease in ERRα expression. CONCLUSIONS: ERRα activity is required to increase expression of PGC-1 isoforms and downstream target genes as part of the adaptive response of contracting adult cardiomyocytes to sustained hypoxia.

Analysis of the operation of on farm emergency slaughter of bovine animals in the Republic of Ireland.

BACKGROUND: On Farm Emergency Slaughter (OFES) is the slaughter outside the slaughterhouse, of an otherwise healthy animal, which has suffered an accident that, for welfare reasons, prevented its transport to a slaughterhouse. The procedure is designed to prevent the transport of welfare compromised animals, which may have veterinary certification to slaughterhouses for Casualty Slaughter (CS), and provides an alternative to the euthanasia and disposal of injured animals that are otherwise fit for human consumption. The aim of this study was to analyse the operation of OFES in the Republic of Ireland between 1st January 2011 and 31st December 2013. METHODS: Data were obtained from the Animal Identification and Movement electronic database of the Department of Agriculture, Food and the Marine. Two structured surveys were designed, one for Official Veterinarians (OVs) who work in slaughterhouses and the second for Private Veterinary Practitioners (PVPs) who work in food animal practice in the Republic of Ireland. Surveys were administered through SurveyMonkey. The total number of bovines slaughtered and the number that underwent OFES in Northern Ireland and the Netherlands were obtained from the Northern Ireland Department of Agriculture and Rural Development and the Netherlands Food and Consumer Safety Authority. RESULTS: OFES is neither widely available nor used in the Republic of Ireland. Results from the OV survey showed that Food Business Operators consider that facilitation of OFES would be detrimental to business. Data from the 5 slaughterhouses which offer OFES showed that acceptance criteria are not standardised. Results from the PVP survey showed that 77 % (n = 79) of PVPs were willing to certify animals for OFES. Fifty four percent (n = 49) were aware of slaughterhouses in their area that provided the service of OFES and 64 % (n = 57) stated a willingness to certify the transport of acutely injured animals to slaughterhouses for CS. Data from the Northern Ireland Department of Agriculture and Rural Development and the Netherlands Food and Consumer Safety Authority indicated a low level of uptake of OFES in the Republic of Ireland compared to Northern Ireland and the Netherlands. CONCLUSION: Based on results reported here, criteria for assessment of risk associated with accepting animals for OFES should be reconsidered. A review of the systems pertaining to OFES and its implementation should be undertaken, including the level and quality of training of all stakeholders, with a view to making OFES more widely available in the Republic of Ireland.

Arrestin-dependent angiotensin AT1 receptor signaling regulates Akt and mTor-mediated protein synthesis.

Control of protein synthesis is critical to both cell growth and proliferation. The mammalian target of rapamycin (mTOR) integrates upstream growth, proliferation, and survival signals, including those transmitted via ERK1/2 and Akt, to regulate the rate of protein translation. The angiotensin AT1 receptor has been shown to activate both ERK1/2 and Akt in arrestin-based signalsomes. Here, we examine the role of arrestin-dependent regulation of ERK1/2 and Akt in the stimulation of mTOR-dependent protein translation by the AT1 receptor using HEK293 and primary vascular smooth muscle cell models. Nascent protein synthesis stimulated by both the canonical AT1 receptor agonist angiotensin II (AngII), and the arrestin pathway-selective agonist [Sar(1)-Ile(4)-Ile(8)]AngII (SII), is blocked by shRNA silencing of ßarrestin1/2 or pharmacological inhibition of Akt, ERK1/2, or mTORC1. In HEK293 cells, SII activates a discrete arrestin-bound pool of Akt and promotes Akt-dependent phosphorylation of mTOR and its downstream effector p70/p85 ribosomal S6 kinase (p70/85S6K). In parallel, SII-activated ERK1/2 helps promote mTOR and p70/85S6K phosphorylation, and is required for phosphorylation of the known ERK1/2 substrate p90 ribosomal S6 kinase (p90RSK). Thus, arrestins coordinate AT1 receptor regulation of ERK1/2 and Akt activity and stimulate protein translation via both Akt-mTOR-p70/85S6K and ERK1/2-p90RSK pathways. These results suggest that in vivo, arrestin pathway-selective AT1 receptor agonists may promote cell growth or hypertrophy through arrestin-mediated mechanisms despite their antagonism of G protein signaling.

Targeted overexpression of tissue inhibitor of matrix metalloproteinase-4 modifies post-myocardial infarction remodeling in mice.

RATIONALE: Myocardial infarction (MI) causes an imbalance between matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases (TIMPs) and is associated with adverse left ventricular (LV) remodeling. A uniform reduction in TIMP-4 post-MI has been observed. OBJECTIVE: To examine post-MI remodeling with cardiac-restricted overexpression of TIMP-4, either through a transgenic or viral delivery approach. METHODS AND RESULTS: MI was induced in mice and then randomized to targeted injection of an adenoviral construct (10 µL; 8×10(9) plaque forming units/mL) encoding green fluorescent protein (GFP) and the full-length human TIMP-4 (Ad-GFP-TIMP4) or GFP. A transgenic construct with cardiac-restricted overexpression TIMP-4 (hTIMP-4exp) was used in a parallel set of studies. LV end-diastolic volume, an index of LV remodeling, increased by >60% from baseline at 5 days post-MI and by >100% at 21 days post-MI in the Ad-GFP only group. However, LV dilation was reduced by ≈50% in both the Ad-GFP-TIMP4 and hTIMP-4exp groups at these post-MI time points. LV ejection fraction was improved with either Ad-GFP-TIMP-4 or hTIMP-4exp. Fibrillar collagen expression and content were increased within the MI region with both TIMP-4 interventions, suggestive of matrix stabilization. CONCLUSIONS: This study is the first to demonstrate that selective myocardial targeting for TIMP-4 induction through either a viral or transgenic approach favorably altered the course of adverse LV remodeling post-MI. Thus, localized induction of endogenous matrix metalloproteinase inhibitors, such as TIMP-4, holds promise as a means to interrupt the progression of post-MI remodeling.

Whose IQ is it?--Assessor bias variance in high-stakes psychological assessment.

Assessor bias variance exists for a psychological measure when some appreciable portion of the score variation that is assumed to reflect examinees' individual differences (i.e., the relevant phenomena in most psychological assessments) instead reflects differences among the examiners who perform the assessment. Ordinary test reliability estimates and standard errors of measurement do not inherently encompass assessor bias variance. This article reports on the application of multilevel linear modeling to examine the presence and extent of assessor bias in the administration of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) for a sample of 2,783 children evaluated by 448 regional school psychologists for high-stakes special education classification purposes. It was found that nearly all WISC-IV scores conveyed significant and nontrivial amounts of variation that had nothing to do with children's actual individual differences and that the Full Scale IQ and Verbal Comprehension Index scores evidenced quite substantial assessor bias. Implications are explored.

Comparison of groups with different patterns of symptom cluster intensity across the breast cancer treatment trajectory.

BACKGROUND: Comparing subgroups with different patterns of change in symptom intensity would assist in sorting out individuals at risk for more severe symptoms and worse functional outcomes. OBJECTIVES: The objectives of this study were to identify and compare subgroups of breast cancer patients with different patterns of change in a psychoneurological symptom cluster intensity across the treatment trajectory. METHODS: This secondary analysis used the data from 160 breast cancer patients undergoing chemotherapy or radiation treatment. Psychoneurological symptom cluster intensity was a composite score of 5 symptoms (depressed mood, cognitive disturbance, fatigue, insomnia, and pain) in a psychoneurological cluster at each of 3 time points (ie, at baseline and at 2 follow-ups after chemotherapy or radiation treatment). RESULTS: Five distinct subgroups representing different patterns of psychoneurological symptom cluster intensity during breast cancer treatment were identified: the gradually increasing pattern subgroup (group 1), the constantly low pattern subgroup (group 2), the start low with dramatic increase and decrease pattern subgroup (group 3), the constantly high pattern subgroup (group 4), and the start high with dramatic decrease and leveling pattern subgroup (group 5). Patients without previous cancer treatment experience, with higher level of education, treated with chemotherapy, and/or with more limitations at the baseline were more likely to follow the pattern group 4. Patients in group 4 had the most serious functional limitations measured at the second follow-up time point. CONCLUSION: The results suggest the need to evaluate interventions for specific subgroups and to examine the causal mechanisms underlying a psychoneurological symptom cluster. IMPLICATION: Clinicians should consider these diverse symptom experiences for assessment/management.

Longitudinal stability of IRT and equivalent-groups linear and equipercentile equating.

A multiscale criterion-referenced test that featured two presumably equivalent forms (A and B), was administered to 1,667 Head Start children at each of four points over an academic year. Using a randomly equivalent groups design, three equating methods were applied: common-item IRT equating using concurrent calibration, linear transformation, and equipercentile transformation. The methods were compared by examining mean score differences, weighted mean squared difference, and Kolmogorov's D statistics for each subscale. The results indicated that over time the IRT equating method and conventional equating methods exhibited different patterns of discrepancy between the two test forms. IRT equating yielded marginally smaller form-to-form mean score differences and generated slightly fewer distributional discrepancies between Forms A and B than both linear and equipercentile equating. However, the results were mixed indicating that more studies are needed to provide additional information on the relative merits and weaknesses of each approach.