Fitting parametric random effects models in very large data sets with application to VHA national data

<p>Abstract</p> <p>Background</p> <p>With the current focus on personalized medicine, patient/subject level inference is often of key interest in translational research. As a result, random effects models (REM) are becoming popular for patient level inference. However, for very large data sets that are characterized by large sample size, it can be difficult to fit REM using commonly available statistical software such as SAS since they require inordinate amounts of computer time and memory allocations beyond what are available preventing model convergence. For example, in a retrospective cohort study of over 800,000 Veterans with type 2 diabetes with longitudinal data over 5 years, fitting REM via generalized linear mixed modeling using currently available standard procedures in SAS (e.g. PROC GLIMMIX) was very difficult and same problems exist in Stata’s gllamm or R’s lme packages. Thus, this study proposes and assesses the performance of a meta regression approach and makes comparison with methods based on sampling of the full data.</p> <p>Data</p> <p>We use both simulated and real data from a national cohort of Veterans with type 2 diabetes (n=890,394) which was created by linking multiple patient and administrative files resulting in a cohort with longitudinal data collected over 5 years.</p> <p>Methods and results</p> <p>The outcome of interest was mean annual HbA1c measured over a 5 years period. Using this outcome, we compared parameter estimates from the proposed random effects meta regression (REMR) with estimates based on simple random sampling and VISN (Veterans Integrated Service Networks) based stratified sampling of the full data. Our results indicate that REMR provides parameter estimates that are less likely to be biased with tighter confidence intervals when the VISN level estimates are homogenous.</p> <p>Conclusion</p> <p>When the interest is to fit REM in repeated measures data with very large sample size, REMR can be used as a good alternative. It leads to reasonable inference for both Gaussian and non-Gaussian responses if parameter estimates are homogeneous across VISNs.</p

Northern Bobwhite Response to Control of Red Imported Fire Ants in the Gulf Coast Prairie of Texas

The population decline of northern bobwhite (Colinus virginianus; hereafter, bobwhite) on the Texas Gulf Coast Prairie, USA is largely attributed to habitat loss. However, red imported fire ants (Solenopsis invicta) occur throughout the region and are considered a possible contributing factor to the bobwhite decline. The objectives of our study were to determine the influence of red imported fire ants on bobwhites by comparing bobwhite nest success, survival, and density between sites treated with fire ant bait (treatment) and reference (control) sites. Our study was conducted on 3 private ranches in Goliad and Refugio counties, Texas. Each ranch contained 2 paired experimental units that consisted of a treatment and control site (500 ha each). The treatment sites received an aerial application of fire ant bait (Extinguish® Plus) during April 2018, whereas the control sites were not treated. We estimated mound density by counting fire ant mounds using distance sampling. We used radio-telemetry to monitor bobwhite nest success and survival, and we estimated bobwhite densities using distance sampling via helicopter surveys. Fire ant mound density decreased through time on both treatment and control sites. However, fire ant mound density was lower on treatment sites than control sites, indicating the insecticide was effective at decreasing fire ant mound density. Bobwhite survival, nest success, and density did not statistically differ between control and treated sites either pre-treatment (2017) or post-treatment (2018), but survival and nest success metrics were numerically higher in treated units. Bobwhite survival remained relatively stable in the treatment units 4 weeks after application but decreased in the control units. Following treatment, apparent nest success in the treated units increased by 37.4% while nest success in the control units decreased by 35.2%. Bobwhite populations were low in this ecoregion, which influenced our ability to trap and monitor many bobwhites or monitor many nests. In addition, it may be possible that repeated, annual treatments for fire ants are necessary for a benefit to accrue and be observed in bobwhites. Our results indicate that there may be potential benefits to bobwhites from fire ant reduction that deserve further research attention

Novel actions of next-generation taxanes benefit advanced stages of prostate cancer.

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro and in xenograft tumors for cabazitaxel response. RESULTS: The data herein show that (i) cabazitaxel exerts stronger cytostatic and cytotoxic response compared with docetaxel, especially in CRPC; (ii) cabazitaxel induces aberrant mitosis, leading to pyknotic and multinucleated cells; (iii) taxanes do not act through the androgen receptor (AR); (iv) gene-expression profiling reveals distinct molecular actions for cabazitaxel; and (v) tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to cabazitaxel. CONCLUSIONS: Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases

Effective translation of the second cistron in two Drosophila dicistronic transcripts is determined by the absence of in-frame AUG codons in the first cistron

The novel dicistronic transcript encoded by the Drosophila melanogaster stoned gene was recognized as being unusual in that the protein encoded by the first open reading frame, stoned-A (STNA), contains no internal methionine residues in a protein of 93 kDa. The dicistronic nature of the stoned locus and the lack of methionine residues in STNA is conserved across dipteran species. A second methionine-free cistron, encoding Snapin, was identified in Drosophila and also found to be dicistronic, the second open reading frame (ORF) encoding a methyltransferase. We have replaced the methyltransferase cistron with green fluorescent protein (GFP) and used this dicistronic construct to show that the GFP cistron is translated in Drosophila S2 cells. The insertion of in-frame AUG codons into the snapin ORF attenuates the translation of GFP, and the level of attenuation correlates with the number of inserted AUGs. Increasing the efficiency of translation-initiation of the Snapin cistron also attenuates the translation of GFP. This indicates that failure to initiate translation at the first AUG allows ribosomes to scan through the Snapin ORF and to initiate translation of the second cistron, unless new AUG codons are inserted. These data are used to interpret the expression of the stoned locus and in particular, to explain the altered stoned protein levels in the stoned-temperature-sensitive mutant allele, which replaces a lysine with a methionine codon early in the first, stonedA, cistron

The Immediate Effects of Expert and Dyad External Focus Feedback on Drop Landing Biomechanics in Female Athletes: An Instrumented Field Study

# Background Anterior Cruciate Ligament (ACL) injury prevention interventions have used trained experts to ensure quality feedback. Dyad (peer) feedback may be a more cost-effective method to deliver feedback to athletes. # Purpose To determine the immediate effects of dyad versus expert feedback on drop landing kinematics and kinetics in female athletes. # Study Design Cohort study # Setting College gymnasium # Methods Two teams (one female basketball and one female volleyball), from a local college, were team randomized to dyad feedback (volleyball team) or expert feedback (basketball team) (13 expert, 19±0.87years, 1.7±0.09m, 68.04±7.21kg) (10 dyad 19.4±1.07years, 1.73±0.08m, 72.18±11.23kg). Participants completed drop vertical jumps at two different time points (pre- and post-feedback). Knee flexion and abduction displacement were assessed with Inertial Measurement Units (IMUs) and vertical ground reaction force (vGRF) was assessed with a force plate during the landing phase of the drop vertical jump and compared across groups and condition (pre- and post-feedback) with a repeated measures ANCOVA *a priori* α <0.02 was set for multiple tests conducted. # Results There were no significant differences between groups for flexion displacement. There was a significant change pre- to post- (decrease 4.65˚ p=0.01) in abduction displacement, with no group effect. There was a significant interaction of group by condition (p=0.01) for vGRF with no difference between groups before feedback (p>0.05). Between groups there was a decrease of vGRF in the expert group (difference 0.45 N\*bw-1, p=0.01) at post-feedback relative to dyad. Within the expert group there was a significant difference between pre- and post-feedback (difference 0.72 N\*bw-1, p=0.01), while the dyad group did not change pre- to post-feedback (difference 0.18 N\*bw-1, p=0.67). # Conclusion Movement screening experts giving real-time feedback were successful in improving key injury-risk kinematics and kinetics in female athletes, while dyad feedback only improved kinematics, indicating that expert feedback may be needed to ensure changes in kinematics and kinetics. # Level of Evidence

The impact of supportive nursing care on the needs of men with prostate cancer: a study across seven European countries

Background: prostate cancer is for many men a chronic disease with a long life expectancy after treatment. The impact of prostate cancer therapy on men has been well defined, however, explanation of the consequences of cancer treatment has not been modelled against the wider variables of long-term health-care provision. The aim of this study was to explore the parameters of unmet supportive care needs in men with prostate cancer in relation to the experience of nursing care. Methods: a survey was conducted among a volunteer sample of 1001 men with prostate cancer living in seven European countries. Results: at the time of the survey, 81% of the men had some unmet supportive care needs including psychological, sexual and health system and information needs. Logistic regression indicated that lack of post-treatment nursing care significantly predicted unmet need. Critically, men's contact with nurses and/or receipt of advice and support from nurses, for several different aspects of nursing care significantly had an impact on men's outcomes. Conclusion: Unmet need is related not only to disease and treatment factors but is also associated with the supportive care men received. Imperative to improving men's treatment outcomes is to also consider the access to nursing and the components of supportive care provided, especially after therapy

The roles of specialist provision for children with specific speech and language difficulties in England and Wales: a model for inclusion?

Children with specific speech and language difficulties pose a challenge to the education and health systems. In addition to their language difficulties they are also at risk of literacy and social, emotional and behavioural difficulties. The main support for children with more severe difficulties has been enhanced provision in mainstream schools (language units or integrated resources) and special schools. The move to an inclusive education system challenges this tradition. The present paper reports the results of interviews with heads of language units/integrated resources and headteachers of special schools (n=57) as part of a larger study within England and Wales. Their views are considered with reference to criteria for entry to specialist provision, the development of collaborative practice between teachers, teaching assistants and speech and language therapists, and the implications for inclusive education

A Decolonial Critique of the Racialized “Localwashing” of Extraction in Central Africa

Responding to calls for increased attention to actions and reactions “from above” within the extractive industry, we offer a decolonial critique of the ways in which corporate entities and multinational institutions propagate racialized rhetoric of “local” suffering, “local” consultation, and “local” fault for failure in extractive zones. Such rhetoric functions to legitimize extractive intervention within a set of practices that we call localwashing. Drawing from a decade of research on and along the Chad-Cameroon Oil Pipeline, we show how multi-scalar actors converged to assert knowledge of, responsibility for, and collaborations with “local” people within a racialized politics of scale. These corporate representations of the racialized “local” are coded through long-standing colonial tropes. We identify three interrelated and overlapping flexian elite rhetoric(s) and practices of racialized localwashing: (a) anguishing, (b) arrogating, and (c) admonishing. These elite representations of a racialized “local” reveal diversionary efforts “from above” to manage public opinion, displace blame for project failures, and domesticate dissent in a context of persistent scrutiny and criticism from international and regional advocates and activists

Improved Standardization of Type II-P Supernovae: Application to an Expanded Sample

In the epoch of precise and accurate cosmology, cross-confirmation using a variety of cosmographic methods is paramount to circumvent systematic uncertainties. Owing to progenitor histories and explosion physics differing from those of Type Ia SNe (SNe Ia), Type II-plateau supernovae (SNe II-P) are unlikely to be affected by evolution in the same way. Based on a new analysis of 17 SNe II-P, and on an improved methodology, we find that SNe II-P are good standardizable candles, almost comparable to SNe Ia. We derive a tight Hubble diagram with a dispersion of 10% in distance, using the simple correlation between luminosity and photospheric velocity introduced by Hamuy & Pinto 2002. We show that the descendent method of Nugent et al. 2006 can be further simplified and that the correction for dust extinction has low statistical impact. We find that our SN sample favors, on average, a very steep dust law with total to selective extinction R_V<2. Such an extinction law has been recently inferred for many SNe Ia. Our results indicate that a distance measurement can be obtained with a single spectrum of a SN II-P during the plateau phase combined with sparse photometric measurements.Comment: ApJ accepted version. Minor change