© 2014 International Institute of Forecasters. We propose a new tool, the Generalized Autocontour (G-ACR), as the basis for a battery of dynamic specification tests that are applicable (in-sample or out-of-sample) to univariate or multivariate random processes. We apply this methodology to the modeling of a multivariate system by specifying the dynamics of the marginal distributions of each process in the system, together with a copula that ties up the marginals to produce their multivariate distribution. We work with the probability integral transforms (PIT) of the system that, under a correct specification of the conditional model, should be i.i.d.U[0,1]. The dimensionality of the system is not a constraint, because the information contained in the vector of PITs is condensed into an indicator, which is the basis of the proposed tests. We construct hyper-cubes of different sizes within the max imum hyper-cube formed by a multidimensional uniform density [0, 1] < sup > n < /sup > , and assess the locations of the empirical PITs (duplex, triplex, n-plex of observations) within the corresponding population hyper-cubes. If the conditional model is correct, the volumes of the population hyper-cubes must be the same as those in their empirical counterparts. This approach allows the researcher to focus on different areas of the conditional density model, so as to assess the regions of interest. We estimate a trivariate model for a very large number of trades on the stocks of three large U.S. banks and find that the contemporaneous dependence among institutions is asymmetric, which implies that when liquidity drains (due to a lack of trading) in one institution, we should expect a concurrent effect among similar institutions. On the other hand, when liquidity is plentiful (due to dense trading), the trades on the stocks of the institutions are not correlated. We assess the models' performances by evaluating their one-step-ahead density forecasts of trades.

ABSTRACT

Motile cells migrate directionally in the electric field in a process known as galvanotaxis. Galvanotaxis is important in wound healing, development, cell division, and nerve growth. Different cell types migrate in opposite directions in electric fields, to either cathode, or anode, and the same cell can switch the directionality depending on chemical conditions. We previously reported that individual fish keratocyte cells sense electric fields and migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Many physiological processes rely on collective, not individual, cell migration, so here we report on directional migration of cohesive cell groups in electric fields. Uninhibited cell groups of any size move to the cathode, with speed decreasing and directionality increasing with the group size. Surprisingly, large groups of PI3K-inhibited cells move to the cathode, in the direction opposite to that of individual cells, which move to the anode, while such small groups are not persistently directional. In the large groups, cells’ velocities are distributed unevenly: the fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. Our results are most consistent with the hypothesis, supported by the computational model, that cells inside and at the edge of the groups interpret directional signals differently. Namely, cells in the group interior are directed to the cathode independently of their chemical state. Meanwhile, edge cells behave like the individual cells: they are directed to the cathode/anode in uninhibited/PI3K-inhibited groups, respectively. As a result, all cells drive uninhibited groups to the cathode, but a mechanical tug-of-war between the inner and edge cells directs large PI3K-inhibited groups with cell majority in the interior to the cathode, while rendering small groups non-directional.

Significance statement

Motile cells migrate directionally in electric fields. This behavior – galvanotaxis – is important in many physiological phenomena. Individual fish keratocytes migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Uninhibited cell groups move to the cathode. Surprisingly, large groups of PI3K-inhibited cells also move to the cathode, in the direction opposite to that of individual cells. The fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. We posit that inner and edge cells interpret directional signals differently, and that a tug-of-war between the edge and inner cells directs the cell groups. These results shed light on general principles of collective cell migration.

A cDNA encoding the 180-kD canine ribosome receptor (RRp) was cloned and sequenced. The deduced primary structure indicates three distinct domains: an NH2-terminal stretch of 28 uncharged amino acids representing the membrane anchor, a basic region (pI = 10.74) comprising the remainder of the NH2-terminal half and an acidic COOH-terminal half (pI = 4.99). The most striking feature of the amino acid sequence is a 10-amino acid consensus motif, NQGKKAEGAP, repeated 54 times in tandem without interruption in the NH2-terminal positively charged region. We postulate that this repeated sequence represents a ribosome binding domain which mediates the interaction between the ribosome and the ER membrane. To substantiate this hypothesis, recombinant full-length ribosome receptor and two truncated versions of this protein, one lacking the potential ribosome binding domain, and one lacking the COOH terminus, were expressed in Saccharomyces cerevisiae. Morphological and biochemical analyses showed all proteins were targeted to, and oriented correctly in the ER membrane. In vitro ribosome binding assays demonstrated that yeast microsomes containing the full-length canine receptor or one lacking the COOH-terminal domain were able to bind two to four times as many human ribosomes as control membranes lacking a recombinant protein or microsomes containing a receptor lacking the NH2-terminal basic domain. Electron micrographs of these cells revealed that the expression of all receptor constructs led to a proliferation of perinuclear ER membranes known as "karmellae." Strikingly, in those strains which expressed cDNAs encoding a receptor containing the putative ribosome binding domain, the induced ER membranes (examined in situ) were richly studded with ribosomes. In contrast, karmellae resulting from the expression of receptor cDNA lacking the putative ribosome binding domain were uniformly smooth and free of ribosomes. Cell fractionation and biochemical analyses corroborated the morphological characterization. Taken together these data provide further evidence that RRp functions as a ribosome receptor in vitro, provide new evidence indicating its functionality in vivo, and in both cases indicate that the NH2-terminal basic domain is essential for ribosome binding.

Background/objective

Guidelines recommend less intensive glycemic treatment and less frequent glucose monitoring for nursing home (NH) residents. However, little is known about the frequency of fingerstick (FS) glucose monitoring in this population. Our objective was to examine the frequency of FS glucose monitoring in Veterans Affairs (VA) NH residents with diabetes mellitus, type II (T2DM).

Design and setting

National retrospective cohort study in 140 VA NHs.

Participants

NH residents with T2DM and older than 65 years admitted to VA NHs between 2013 and 2015 following discharge from a VA hospital.

Measurements

NH residents were classified into five groups based on their highest hypoglycemia risk glucose-lowering medication (GLM) each day: no GLMs; metformin only; sulfonylureas; long-acting insulin; and any short-acting insulin. Our outcome was a daily count of FS measurements.

Results

Among 17,474 VA NH residents, mean age was 76 (standard deviation (SD) = 8) years and mean hemoglobin A1c was 7.6% (SD = 1.5%). On day 1 after NH admission, 49% of NH residents were on short-acting insulin, decreasing slightly to 43% at day 90. Overall, NH residents had an average of 1.9 (95% confidence interval (CI) = 1.8-1.9) FS measurements on NH day 1, decreasing to 1.4 (95% CI = 1.3-1.4) by day 90. NH residents on short-acting insulin had the most frequent FS measurements, with 3.0 measurements (95% CI = 2.9-3.0) on day 1, decreasing to 2.6 measurements (95% CI = 2.5-2.7) by day 90. Less frequent FS measurements were seen for NH residents receiving long-acting insulin (2.1 (95% CI = 2.0-2.2) on day 1) and sulfonylureas (1.7 (95% CI = 1.5-1.8) on day 1). Even NH residents on metformin monotherapy had 1.1 (95% CI = 1.1-1.2) measurements on day 1, decreasing to 0.5 (95% CI = 0.4-0.6) measurements on day 90.

Conclusion

Although guidelines recommend less frequent glucose monitoring for NH residents, we found that many VA NH residents receive frequent FS monitoring. Given the uncertain benefits and potential for substantial patient burdens and harms, our results suggest decreasing FS monitoring may be warranted for many low hypoglycemia risk NH residents.

Various thermal-hydrologic models have been developed to simulate thermal-hydrologic conditions in emplacement drifts and surrounding host rock for the proposed high-level nuclear waste repository at Yucca Mountain, Nevada. The modeling involves two-phase (liquid and gas) and two-component (water and air) transport in a fractured-rock system, which is conceptualized as a dual-permeability medium. Simulated hydrologic processes depend upon calibrated system parameters, such as the van Genuchten α and m, which quantify the capillary properties of the fractures and rock matrix. Typically, these parameters are not calibrated for strongly heat-driven conditions, i.e., conditions for which boiling and rock dryout occur. The objective of this study is to modify the relationship between capillary pressure and saturation, P c(S), for strongly heated conditions that drive saturation below the residual saturation (S → 0). We offer various extensions to the van Genuchten capillary-pressure function and compare results from a thermal-hydrologic model with data collected during the Drift-Scale Test, an in situ thermal test at Yucca Mountain, to investigate the suitability of these various P c extension methods. The study suggests that the use of extension methods and the imposition of a capillary-pressure cap (or maximum) improve the agreement between Drift-Scale Test data and model results for strongly heat-driven conditions. However, for thermal-hydrologic models of the Yucca Mountain nuclear waste repository, temperature and relative humidity are insensitive to the choice of extension method for the capillary-pressure function. Therefore, the choice of extension method applied to models of drift-scale thermal-hydrologic behavior at Yucca Mountain can be made on the basis of numerical performance.

Background

Guidelines recommend breast and colorectal cancer screening for older adults with a life expectancy >10 years. Most mortality indexes require clinician data entry, presenting a barrier for routine use in care. Electronic health records (EHR) are a rich clinical data source that could be used to create individualized life expectancy predictions to identify patients for cancer screening without data entry.

Objective

To develop and internally validate a life expectancy calculator from structured EHR data.

Design

Retrospective cohort study using national Veteran's Affairs (VA) EHR databases.

Patients

Veterans aged 50+ with a primary care visit during 2005.

Main measures

We assessed demographics, diseases, medications, laboratory results, healthcare utilization, and vital signs 1 year prior to the index visit. Mortality follow-up was complete through 2017. Using the development cohort (80% sample), we used LASSO Cox regression to select ~100 predictors from 913 EHR data elements. In the validation cohort (remaining 20% sample), we calculated the integrated area under the curve (iAUC) and evaluated calibration.

Key results

In 3,705,122 patients, the mean age was 68 years and the majority were male (97%) and white (85%); nearly half (49%) died. The life expectancy calculator included 93 predictors; age and gender most strongly contributed to discrimination; diseases also contributed significantly while vital signs were negligible. The iAUC was 0.816 (95% confidence interval, 0.815, 0.817) with good calibration.

Conclusions

We developed a life expectancy calculator using VA EHR data with excellent discrimination and calibration. Automated life expectancy prediction using EHR data may improve guideline-concordant breast and colorectal cancer screening by identifying patients with a life expectancy >10 years.

Background

Limited evidence exists on how women's experiences of care, specifically person-centered maternity care during childbirth, influence maternal and newborn health outcomes.

Objective

This study aimed to examine the associations between person-centered maternity care and maternal and newborn health outcomes.

Study design

Longitudinal data were collected with 1014 women who completed baseline at a health facility and followed up at 2 weeks and 10 weeks after birth. A validated 30-item person-centered maternity care scale was administered to postpartum women within 48 hours after childbirth. The person-centered maternity care scale has 3 subscales: dignity and respect, communication and autonomy, and supportive care. Bivariate and multivariable log Poisson regressions were used to examine the relationship between person-centered maternity care and reported maternal complications, newborn complications, postpartum depression, postpartum family planning uptake, exclusive breastfeeding, and newborn immunizations.

Results

Controlling for demographic characteristics, women with high total person-centered maternity care score at baseline had significantly lower risk of reporting maternal complications (adjusted relative risk, 0.63; 95% confidence interval, 0.42-0.95), screening positive for depression (adjusted relative risk, 0.55; 95% confidence interval, 0.38-0.81), and reporting newborn complications (adjusted relative risk, 0.74; 95% confidence interval, 0.56-0.97), respectively, than women with low total person-centered maternity care scores. Women with high scores on the supportive care subscale had significantly lower risk of reporting maternal and newborn complications than women with low scores on these subscales (adjusted relative risk, 0.52 [95% confidence interval, 0.42-0.65] and 0.74 [95% confidence interval, 0.60-0.91], respectively). Significant associations were found between all 3 subscale scores and screening positive for depression. Women with high total person-centered maternity care scores were also more likely to adopt a family planning method than those with low scores (adjusted relative risk, 1.25; 95% confidence interval, 1.02-1.52). In particular, women with high scores on the communication and autonomy subscale had significantly higher odds of adopting a family planning method than women with low scores (risk ratio, 1.15; 95% confidence interval, 1.08-1.23).

Conclusion

Improving person-centered maternity care may improve maternal and newborn health outcomes. Specifically, improving supportive care may decrease the risk of maternal and newborn complications, whereas improving communication and autonomy may increase postpartum family planning uptake.