Probit models for capture-recapture data subject to imperfect detection, individual heterogeneity and misidentification

As noninvasive sampling techniques for animal populations have become more popular, there has been increasing interest in the development of capture-recapture models that can accommodate both imperfect detection and misidentification of individuals (e.g., due to genotyping error). However, current methods do not allow for individual variation in parameters, such as detection or survival probability. Here we develop misidentification models for capture-recapture data that can simultaneously account for temporal variation, behavioral effects and individual heterogeneity in parameters. To facilitate Bayesian inference using our approach, we extend standard probit regression techniques to latent multinomial models where the dimension and zeros of the response cannot be observed. We also present a novel Metropolis-Hastings within Gibbs algorithm for fitting these models using Markov chain Monte Carlo. Using closed population abundance models for illustration, we re-visit a DNA capture-recapture population study of black bears in Michigan, USA and find evidence of misidentification due to genotyping error, as well as temporal, behavioral and individual variation in detection probability. We also estimate a salamander population of known size from laboratory experiments evaluating the effectiveness of a marking technique commonly used for amphibians and fish. Our model was able to reliably estimate the size of this population and provided evidence of individual heterogeneity in misidentification probability that is attributable to variable mark quality. Our approach is more computationally demanding than previously proposed methods, but it provides the flexibility necessary for a much broader suite of models to be explored while properly accounting for uncertainty introduced by misidentification and imperfect detection. In the absence of misidentification, our probit formulation also provides a convenient and efficient Gibbs sampler for Bayesian analysis of traditional closed population capture-recapture data.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS783 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Improving Physiological Relevance of Cell Culture: The Possibilities, Considerations and Future Directions of the Ex Vivo Co-Culture Model

In vitro models provide an important platform for the investigation of cellular growth and atrophy to inform, or extend mechanistic insights from, logistically challenging in vivo trials. While these models allow for the identification of candidate mechanistic pathways, many models involve supraphysiological dosages, non-physiological conditions, or experimental changes relating to individual proteins or receptors, all of which limit translation to human trials. To overcome these drawbacks, the use of ex vivo human plasma and serum has been used in cellular models to investigate changes in myotube hypertrophy, cellular protein synthesis, anabolic and catabolic markers in response to differing age, disease states, and nutrient status. However, there are currently no concurrent guidelines outlining the optimal methodology for this model. This review discusses the key methodological considerations surrounding the use of ex vivoplasma and serum, with a focus in application to skeletal muscle cell lines (i.e., C2C12, L6 and LHCN-M2) and human primary skeletal muscle cells (HSMC) as a means to investigate molecular signaling in models of atrophy and hypertrophy, alongside future directions

Tibial Tubercle Osteotomy and Medial Patellofemoral Ligament Imbrication for Patellar Instability Due to Trochlear Dysplasia.

BackgroundThe treatment of patellar instability in the setting of trochlear dysplasia is challenging.Purpose/hypothesisThe purpose of this study was to evaluate outcomes for the treatment of recurrent patellar dislocations due to trochlear dysplasia using anteromedialization tibial tubercle osteotomy combined with medial patellofemoral ligament (MPFL) imbrication. We hypothesized that the treatment of patellar instability with tibial tubercle osteotomy and MPFL imbrication would result in improved patient satisfaction and decrease patellar instability events in patients with prior instability and trochlear dysplasia.Study designCase series; Level of evidence, 4.MethodsWe performed a retrospective analysis of patients who underwent MPFL imbrication and concomitant anteromedialization tibial tubercle osteotomy for recurrent patellofemoral instability at a single institution. The minimum follow-up was 1 year. Patient demographic information including age at the time of surgery, sex, body mass index (BMI), tibial tubercle-trochlear groove (TT-TG) distance, and grade of trochlear dysplasia was collected along with relevant operative data. Postoperatively, recurrent dislocation events as well as Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index, and Kujala scores were collected, and satisfaction was ascertained by asking patients whether they would undergo the procedure again.ResultsA total of 37 knees from 31 patients (23 female) with a mean follow-up of 3.8 years (range, 1-8.9 years) were included. The mean patient age was 28.8 years (range, 14-45 years), the mean BMI was 24 kg/m2 (range, 20-38 kg/m2), and the mean preoperative TT-TG distance was 18.9 mm (range, 8.4-32.4 mm). Two knees were classified as low-grade trochlear dysplasia (Dejour A) and 35 as high-grade trochlear dysplasia (Dejour B-D). At final follow-up, patients reported mean KOOS subscale scores of 86.5 (Pain), 79.8 (Symptoms), 93.9 (Activities of Daily Living), 74.3 (Sports/Recreation), and 61.9 (Quality of Life), as well as a mean Kujala score of 81.3. Mean patient satisfaction was 8.3 of 10. The majority of knees (86.5%; 32/37) remained stable without recurrent instability after this procedure, while 13.5% (5 knees) suffered a recurrent dislocation, with 2 requiring revision surgery. Eight knees (21.6%) underwent subsequent hardware removal.ConclusionAnteromedialization tibial tubercle osteotomy with MPFL imbrication can improve recurrent patellofemoral instability and provide significant clinical benefit to patients with trochlear dysplasia

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

BackgroundBudesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis.AimThe aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam.MethodsData from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam.ResultsA similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration.ConclusionsThis integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis

Force balance in canonical ensembles of static granular packings

We investigate the role of local force balance in the transition from a microcanonical ensemble of static granular packings, characterized by an invariant stress, to a canonical ensemble. Packings in two dimensions admit a reciprocal tiling, and a collective effect of force balance is that the area of this tiling is also invariant in a microcanonical ensemble. We present analytical relations between stress, tiling area and tiling area fluctuations, and show that a canonical ensemble can be characterized by an intensive thermodynamic parameter conjugate to one or the other. We test the equivalence of different ensembles through the first canonical simulations of the force network ensemble, a model system.Comment: 9 pages, 9 figures, submitted to JSTA

Large-area submillimeter resolution CdZnTe strip detector for astronomy

We report the first performance measurements of a sub-millimeter CdZnTe strip detector developed as a prototype for space-borne astronomical instruments. Strip detector arrays can be used to provide two-dimensional position resolution with fewer electronic channels than pixellated arrays. Arrays of this type and other candidate technologies are under investigation for the position-sensitive backplane detector for a coded-aperture telescope operating in the range of 30 - 300 keV. The prototype is a 1.4 mm thick, 64 multiplied by 64 stripe CdZnTe array of 0.375 mm pitch in both dimensions, approximately one square inch of sensitive area. Pulse height spectra in both single and orthogonal stripe coincidence mode were recorded at several energies. The results are compared to slab- and pixel-geometry detector spectra. The room-temperature energy resolution is less than 10 keV (FWHM) for 122 keV photons with a peak-to-valley ratio greater than 5:1. The response to photons with energies up to 662 keV appears to be considerably improved relative to that of previously reported slab and pixel detectors. We also show that strip detectors can yield spatial and energy resolutions similar to those of pixellated arrays with the same dimensions. Electrostatic effects on the pulse heights, read-out circuit complexity, and issues related to design of space borne instruments are also discussed

A Holistic Approach to Estimating the Influence of Good Practices on Student Outcomes at Liberal Arts and non-Liberal Arts Institutions

Many higher education administrators and researchers have considered certain “good practices” of institutions as an instrumental way to improve student outcomes. Chickering and Gamson’s (1987) seven principles of good practice has been particularly salient in defining these practices. Often, prior studies only select some of the seven principles for their analysis. Even studies that consider several principles of good practice on student outcomes typically examine the net effect of each principle instead of assessing how these principles holistically influence student out-comes. Using structural equation modeling, we test a basic conceptual framework where we in-vestigate the contribution of the seven principles on a global measure of good practices (GP), as well as the influence of GP on a multitude of student outcomes. We further test whether liberal arts colleges promote an institutional ethos of good practices as compared to non-liberal arts col-leges. Overall, the majority (but not all) of the principles affect GP. Moreover, we find partial evidence that liberal arts colleges foster an institutional ethos of good practices. Although a commitment to foster good practices may create a supportive environment that influences student outcomes, this commitment may lead to unintended consequences for those with little exposure to these good practices

A strained silicon cold electron bolometer using Schottky contacts

We describe optical characterisation of a strained silicon cold electron bolometer (CEB), operating on a 350 mK stage, designed for absorption of millimetre-wave radiation. The silicon cold electron bolometer utilises Schottky contacts between a superconductor and an n++ doped silicon island to detect changes in the temperature of the charge carriers in the silicon, due to variations in absorbed radiation. By using strained silicon as the absorber, we decrease the electron-phonon coupling in the device and increase the responsivity to incoming power. The strained silicon absorber is coupled to a planar aluminium twin-slot antenna designed to couple to 160 GHz and that serves as the superconducting contacts. From the measured optical responsivity and spectral response, we calculate a maximum optical efficiency of 50% for radiation coupled into the device by the planar antenna and an overall noise equivalent power, referred to absorbed optical power, of 1.1×10−16 W Hz−1/2 when the detector is observing a 300 K source through a 4 K throughput limiting aperture. Even though this optical system is not optimized, we measure a system noise equivalent temperature difference of 6 mK Hz−1/2. We measure the noise of the device using a cross-correlation of time stream data, measured simultaneously with two junction field-effect transistor amplifiers, with a base correlated noise level of 300 pV Hz−1/2 and find that the total noise is consistent with a combination of photon noise, current shot noise, and electron-phonon thermal noise

Patient and professional factors that impact the perceived likelihood and confidence of healthcare professionals to discuss Implantable Cardioverter Defibrillator deactivation in advanced heart failure: Results from an international factorial survey

Background: Rate of implantable cardioverter defibrillator (ICD) implantations is increasing in patients with advanced heart failure. Despite clear guideline recommendations, discussions addressing deactivation occur infrequently. Aim: The aim of this article is to explore patient and professional factors that impact perceived likelihood and confidence of healthcare professionals to discuss ICD deactivation. Methods and Results: Between 2015 and 2016, an international sample of 262 healthcare professionals (65% nursing, 24% medical) completed an online factorial survey, encompassing a demographic questionnaire and clinical vignettes. Each vignette had 9 randomly manipulated and embedded patient-related factors, considered as independent variables, providing 1572 unique vignettes for analysis. These factors were determined through synthesis of a systematic literature review, a retrospective case note review, and a qualitative exploratory study. Results showed that most healthcare professionals agreed that deactivation discussions should be initiated by a cardiologist (95%, n = 255) or a specialist nurse (81%, n = 215). In terms of experience, 84% of cardiologists (n = 53) but only 30% of nurses (n = 50) had previously been involved in a deactivation decision. Healthcare professionals valued patient involvement in deactivation decisions; however, only 50% (n = 130) actively involved family members. Five of 9 clinical factors were associated with an increased likelihood to discuss deactivation including advanced age, severe heart failure, presence of malignancy, receipt of multiple ICD shocks, and more than 3 hospital admissions during the previous year. Furthermore, nationality and discipline significantly influenced likelihood and confidence in decision making. Conclusions: Guidelines recommend that healthcare professionals discuss ICD deactivation; however, practice is suboptimal with multifactorial factors impacting on decision making. The role and responsibility of nurses in discussing deactivation require clarity and improvement.Funding Agencies|HFA Nurse Fellowship training grant; Public Health Agency NI (Research &amp; Development Division)</p