Short communication: Utilisation of n-alkanes to estimate feed intake in horses fed known amounts of a labelled concentrate supplement.

The assessment of feed intake in stabled horses is a difficult task to accomplish. Faecal markers, namely n-alkanes, have been used successfully for the estimation of this important nutritional parameter. This usually involves the dosing of synthetic n-alkanes via different matrices, a laborious task that may also influence the animal normal foraging behaviour. An experiment was conducted to evaluate a relative simple methodology to quantify feed intake in horses, based on the provision of measured amounts of a concentrate supplement labelled with beeswax and the utilisation of n-alkanes as faecal markers. Four Lusitano horses were used in three consecutive experimental periods. Animals were fed on cereal straw and different proportions of a previously prepared beeswax-labelled concentrate supplement (BLCS; 0.05, 0.10 and 0.20, DM basis). Beeswax labelling was performed to provide a distinct n-alkane profile for the concentrate feed. Prior to feed intake calculations, proportions of labelled concentrate supplement in the diets were estimated using n-alkanes C25 to C33 by least-square optimisation procedures. Results showed that the beeswax labelling resulted in high n-alkane concentrations in the concentrate feed, especially for the odd-chain n-alkanes. Estimates of diet composition did not differ from the measured values, except for the diet with highest BLCS incorporation, with an underestimation of 10%. DM intake was accurately estimated by the "labelled supplement method" in all diets. However, for the lowest BLCS incorporation, DM intake was underestimated by 16% whereas for the higher levels of BLCS in the diet, measured and estimated DM intake values were almost identical with a slight overestimation of only 0.7 and 0.2% (10 and 20% of BLCS, respectively). Results indicate that both diet composition and feed intake can be accurately estimated in horses using the "labelled supplement method", even when very low levels of the labelled concentrate supplement are included in the animals' diet. This method eliminates the need for daily dosing with external synthetic markers, providing advantages in terms of minimising animal management and interference with their normal foraging behaviour.

Suboptimal Completion Rates, Adverse Events, Costs, Resource Utilization, and Cost Impact of Noncompletion in Oral Adjuvant Capecitabine-Based Chemotherapy in Patients With Early-Stage Colon Cancer.

BACKGROUND: Suboptimal completion of chemotherapy, which may involve reduced patient adherence, remains a serious issue and leads to reduced treatment efficacy. This study assessed the completion rates, risk factors for noncompletion, and cost impact for noncompletion in patients on capecitabine monotherapy (Cape) or capecitabine with oxaliplatin (CAPOX) for the adjuvant treatment of early-stage colon cancer. METHODS: Patients with a diagnosis of early-stage colon cancer between April 2013 and March 2017 were retrospectively identified. Treatment completion was evaluated. Multivariate logistic regressions analyses were used to assess the baseline factors associated with noncompletion. Adverse events, costs, healthcare resource utilization, and cost impact for noncompletion were investigated. RESULTS: A total of 673 patients met the eligibility criteria, of which 382 (57%) were treated with Cape and 291 (43%) with CAPOX. The overall completion rate for adjuvant therapy was 40% (Cape 46%; CAPOX 33%). Noncompletion was associated with CAPOX treatment and higher healthcare costs within 6 months prior to chemotherapy. The 6-month unadjusted total healthcare costs were $44,444 for Cape and $71,247 for CAPOX. The nonchemotherapy costs were 41% higher for noncompleters than completers in both treatment groups (P = .002). CONCLUSIONS: The real-world completion rates for adjuvant capecitabine-based chemotherapy in early-stage colon cancer patients are low. Noncompletion of therapy is associated with higher baseline healthcare costs. The nonchemotherapy costs are significantly higher in noncompleters than completers, highlighting the financial burden of managing adverse events and preexisting comorbidities, which may lead to early discontinuation of therapy. Effective strategies to optimize completion of oral chemotherapy may consider adherence monitoring.

Reconsidering LINE-1's role in cancer: does LINE-1 function as a reporter detecting early cancer-associated epigenetic signatures?

Long interspersed nuclear element-1 (LINE-1 or L1) is the only autonomously active retrotransposon in humans. While L1 has been implicated in several pathologies and the aging process, I present a model which challenges an understanding of L1 as predominantly antagonistic to human health. I hypothesize that L1 serves as a reporter in an early cancer alert system: a tripwire strung throughout the genome poised to trigger p53 and a type I interferon (IFN-1) response when the epigenetic landscape portends cancer. Cell proliferation and a shift to aerobic glycolysis cause dramatic changes in the epigenome which are permissive to L1's escape from suppression. L1 has several properties which make it particularly apt to fulfill this hypothesized sentinel function. Being present in many copies spread throughout the genome allows it to monitor many regions for epigenetic instability and renders it robust to deactivation by mutation. This proposed cancer alert system would alter the cancer cell fitness landscape discouraging the use of growth-favoring aerobic glycolysis by threatening the activation of tumor-suppressive mechanisms. It also imposes costs on a strategy of non-specific global transcriptional derepression aimed at activating oncogenes. Erroneous activations of this system are predicted to increase the rate of aging, suggesting this represents a case of antagonistic pleiotropy trading prolonged youth for cancer prevention. More research is needed to assess this model. Lay summary: During carcinogenesis the epigenome is remodeled by the Warburg effect and cellular proliferation. These processes globally relax chromatin. This epigenetic environment is permissive to the retrotransposon long interspersed nuclear element-1's (LINE-1 or L1) escape from suppression. I hypothesize and present evidence for the notion that L1 has been co-opted to serve as a reporter in an early cancer alert system, poised to trigger tumor suppressive mechanisms when the epigenetic landscape portends cancer. This hypothesis describes a potentially major means by which transformation is thwarted early on.

Does HIV infection increase male sexual behavior?

After 40 years of intense study on HIV/AIDS, scientists have identified, among other things, at risk populations, stages of disease progression and treatment strategies. What has received less attention is the possibility that infection might elicit an increase in sexual behavior in humans. In 2000, Starks and colleagues speculated that HIV infection could alter host behavior in a manner that facilitated the spread of the virus. Retrospective and self-report data from five studies now support this hypothesis. Individuals with acute-versus nonacute-stage infections report more sexual partners and more frequent risky sex. Additionally, male sexual behavior increases nonlinearly with HIV viral load, and data suggest a potential threshold viral level above which individuals are more likely to engage in risky sexual behavior. Taken together, these data suggest that HIV infection influences male sexual behavior in a manner beneficial to the virus. Here, we present these findings, highlight their limitations and discuss alternative perspectives. We argue for increased testing of this hypothesis and advocate for increased public health measures to mitigate the putative impact on male sexual behavior. Lay Summary In 2000, Starks and colleagues speculated that HIV infection could alter host behavior in a manner that facilitated the spread of the virus. Retrospective and self-report data from five studies now support this hypothesis. We argue for increased testing of this hypothesis and advocate for increased public health measures to mitigate the putative impact on male sexual behavior.

The rates of second lung cancers and the survival of surgically-resected second primary lung cancers in patients undergoing resection of an initial primary lung cancer.

BACKGROUND: The Lung Cancer Screening Trial demonstrated improved overall survival (OS) and lung cancer specific survival (LCSS), likely due to finding early-stage NSCLC. The purpose of our investigation is to evaluate whether long-term surveillance strategies (4+ years after surgical resection of the initial lung cancer(1LC)) would be beneficial in NSCLC patients by assessing the rates of second lung cancers(2LC) and the OS/LCSS in patients undergoing definitive surgery in 1LC as compared to 2LC (>48 months after 1LC) populations. METHODS: SEER13/18 database was reviewed for patients during 1998-2013. Log-rank tests were used to determine the OS/LCSS differences between the 1LC and 2LC in the entire surgical group(EG) and in those having an early-stage resectable tumors (ESR, tumors <4 cm, node negative). Joinpoint analysis was used to determine rates of second cancers 4-10 year after 1LC using SEER-9 during years 1985-2014. RESULTS: The rate of 2LCs was significantly less than all other second cancers until 2001 when the incidence of 2LCs increased sharply and became significantly greater than all other second cancers in females starting in year 2005 and in men starting in year 2010. OS/LCSS, adjusted for propensity score by using inverse probability weighting, demonstrated similar OS, but worse LCSS for 2LCs in the EG, but similar OS/LCSSs in the ESR group. CONCLUSION: Because the rate of 2LCs are increasing and because the OS/LCSS of the 1LC and 2LC are similar in early-stage lesions, we feel that continued surveillance of patients in order to find early-stage disease may be beneficial.

Thoracic aortic geometry correlates with endograft bird-beaking severity.

OBJECTIVE: Aortic geometry has been shown to influence the development of endograft malapposition (bird-beaking) in thoracic endovascular aortic repair (TEVAR), but the extent of this relationship lacks clarity. The aim of this study was to develop a reproducible method of measuring bird-beak severity and to investigate preoperative geometry associated with bird-beaking. METHODS: The study retrospectively analyzed 20 patients with thoracic aortic aneurysms or type B dissections treated with TEVAR. Computed tomography scans were used to construct three-dimensional geometric models of the preoperative and postoperative aorta and endograft. Postoperative bird-beaking was quantified with length, height, and angle; categorized into a bird-beak group (BBG; n = 10) and no bird-beak group (NBBG; n = 10) using bird-beak height ≥5 mm as a threshold; and correlated to preoperative metrics including aortic cross-sectional area, inner curvature, diameter, and inner curvature × diameter as well as graft diameter and oversizing at the proximal landing zone. RESULTS: Aortic area (1002 ± 118 mm2 vs 834 ± 248 mm2), inner curvature (0.040 ± 0.014 mm-1 vs 0.031 ± 0.012 mm-1), and diameter (35.7 ± 2.1 mm vs 32.2 ± 4.9 mm) were not significantly different between BBG and NBBG; however, inner curvature × diameter was significantly higher in BBG (1.4 ± 0.5 vs 1.0 ± 0.3; P = .030). Inner curvature and curvature × diameter were significantly correlated with bird-beak height (R = 0.462, P = .041; R = 0.592, P = .006) and bird-beak angle (R = 0.680, P < .001; R = 0.712, P < .001). CONCLUSIONS: TEVAR bird-beak severity can be quantified and predicted with geometric modeling techniques, and the combination of high preoperative aortic inner curvature and diameter increases the risk for development of TEVAR bird-beaking.

A Systematic Study of Selective Protein Glycation.

Glycation is a non-enzymatic post-translational modification (PTM) that remains poorly understood, largely because it is unknown how it occurs selectively. Using mass spectrometry, it was possible to evaluate total glycation levels, identify distinct glycated products, assign unique glycation sites, and correlate these data with chemical and structural features for a panel of proteins glycated in vitro. It was determined that the extent of glycation does not correlate with pKa or surface exposure at reactive sites. Rather, the data reveal that primary sequence dictates the overall likelihood that a site will become glycated, while surrounding structure further sculpts the glycation outcome. Clustered acidic residues were found to prevent glycation, whereas a combination of tyrosine and polar residues appear to promote glycation. This work contributes important new knowledge about the molecular features that govern selective glycation.

The cycle of violence. Revisited 6 years later.

OBJECTIVE: To assess the long-term effects of child abuse and neglect on delinquency, adult criminality, and violent criminal behavior. DESIGN: Prospective cohorts design that matched cases of abuse and neglect with those of controls. Follow-up data collection at 22 to 26 years following abuse or neglect. SETTING: A metropolitan area in the Midwest. PARTICIPANTS: Substantiated cases of child abuse or neglect identified from court records that were obtained from 1967 through 1971 (n=908). Comparison group matched on the date of birth, race, sex, and approximate social class (n=667). The current mean age was 32.5 years. MAIN OUTCOME MEASURES: Official arrest records for nontraffic and violent crimes collected from local, state, and federal law enforcement agencies through mid-1994. RESULTS: Childhood victims of abuse or neglect were more likely than controls to have a juvenile or adult arrest for any nontraffic offense (49% vs 38%) and for a violent crime (18% vs 14%). Victims of physical abuse and neglected children were more likely to be arrested for violence (odds ratios: 1.9 and 1.6, respectively), after controlling for age, race, and sex. CONCLUSIONS: Childhood abuse and neglect have a significant impact on the likelihood of arrest for delinquency, adult criminality, and violence. By the age of 32 years, almost half of the victims of abuse and neglect were arrested for a nontraffic offense. By responding to incidents of child abuse and neglect, health care professionals can play an important role in preventing future violence. More attention must be paid to childhood victims of neglect and to differences in the consequences of abuse and neglect by gender and race or ethnicity.

Training staff to prevent aggressive behavior of cognitively impaired elderly patients during bathing and grooming.

1. Cognitively impaired elderly patients often become aggressive toward caregivers who are providing assistance with bathing and grooming, but caregivers can learn methods to prevent or reduce some of the aggression. 2. The R.E.S.P.E.C.T. model describes key practices caregivers can use to better meet patient needs and reduce aggression, increasing their understanding and skill. 3. In addition to training, observation of performance and consultation are important steps in enabling caregivers to apply and maintain their skills.

Cost-effectiveness of levonorgestrel subdermal implants. Comparison with other contraceptive methods available in the United States.

The objective of this analysis was to evaluate and compare the cost-effectiveness of eight contraceptive methods: condoms, diaphragms, oral contraceptives, intrauterine devices, medroxyprogesterone acetate suspension, levonorgestrel subdermal implants, tubal ligation and vasectomy. Based on a comprehensive review of the literature and various additional data sources, this analysis identified, measured and compared direct costs of the methods, physician visits, treatment of adverse effects and cost of failure (i.e., mean cost for all types of deliveries or first-trimester abortion). Medical benefits (if any) resulting from each contraceptive method were calculated and considered in the analysis as cost savings. The cost of method failure proved to be the greatest influence on cost-effectiveness. Sterilization was identified as the most cost-effective method overall. Of the reversible methods, the intrauterine device was found to be the most cost-effective, followed by levonorgestrel implants.

PIP: Cost is an important factor which can influence the choice of a particular contraceptive method. Costs affect not only patients, but the ability of social service systems to provide access to contraception. Levonorgestrel implants were approved by the Food and Drug Administration in December 1990 as the first available contraceptive subdermal implant. They have since been inserted in 780,000 women in the US. The authors developed a cost-effectiveness model to evaluate and compare the cost-effectiveness of these implants against those of condoms, diaphragms, oral contraceptives, IUDs, medroxyprogesterone acetate suspension, tubal ligation, and vasectomy. The model identifies, measures, and compares direct costs of the methods, physician visits, the treatment of adverse effects, and cost of failure, thus calculating an expected cost per year for each method. Medical benefits, if any, resulting from the use of each method were calculated and considered in the analysis as cost savings. A sensitivity analysis was performed using cost parameters and failure rates, both independently and in combination. Data for the analysis were drawn from a comprehensive literature review, physician surveys, manufacturer package inserts, 1992 diagnosis-related group hospital reimbursement rates from Medicaid, and physician interviews. The cost of method failure had the greatest influence upon cost-effectiveness, with sterilization identified as the most cost-effective method overall. Of the reversible methods, the IUD was found to be the most cost-effective, followed by levonorgestrel implants.

A commitment to values. A system integrates core values with leadership development.

The Values in Leadership program, a new leadership development program created by the Sisters of Charity Health Care Systems (SCHCS), is designed to empower effective leaders to live out personal values compatible with those of the organization. The program, designed for middle and senior managers, comprises seven educational modules- Living Our Values; Valuing Individual Differences; Leader as Servant; Leader as Visionary; Leader as Catalyst; Leader as Mentor; Formative Leadership; and Leader as Mentor; Motivational Coaching. Throughout the sessions, participants discuss the four roles of an effective leader-servant, visionary, catalyst, and mentor-which are grounded in SCHCS core values. Participants are also challenged to identify specific actions that can be integrated into their leadership styles. These actions, drawn from SCHCS leadership practices and core values, are reinforced when participants return to their jobs and write plans to incorporate these practices into their daily work.

Psychometric prediction of driving performance among the disabled.

A battery of psychometric and performance tests was administered to 25 subjects who were classified into able-bodied (n = 8), brain-injured (n = 10), and spinal cord injured groups (n = 7). All disabled subjects were regarded by their referring rehabilitation therapists as potential candidates for driver assessment. Data were analyzed to identify which measures were useful in differentiating among the groups and predicting driving performance. Results indicated that psychometric measures can be useful in predicting driving performance among disabled drivers. Nearly all the measures in the battery were significant predictors of driving ability, and some were highly predictive. The best was the oral version of the Symbol Digit Modalities test, which by itself accounted for 70% of the variance of the full-sized-vehicle driving score. Adding a second variable into a two-step multiple regression further increased the correlation between predictors and driving, accounting for almost 80% of the variance in driving score. These findings support the feasibility of developing a simple test battery to determine which disabled candidates are ready for in-vehicle assessment, and which candidates are not ready without further evaluation of cognitive and performance skills.

Measures of central tendency, variability, and relative standing in nonnormal distributions: alternatives to the mean and standard score.

There are two major disadvantages to reporting test results in standardized scores such as z-scores or t-scores when describing individuals with disabilities. (1) Raw scores on many tasks from disabled individuals are notoriously nonnormal. They are asymmetric, in that they are skewed toward poor scores. (2) Low z-scores give a false impression of dysfunction because able-bodied subjects are often grossly overqualified for the application in question; they may have levels of strength or quickness several orders of magnitude greater than what is needed to do the assessment task. A recommended alternative is to describe the performance of disabled individuals using nonparametric statistics, and to report scores in boxplots, showing the extremes, the median, and the quartiles. Such points are easy to calculate and to interpret, and they are robust against outliers.

Afterimage color perception for designers.

This is a study of perception of negative afterimages. Surface color samples were viewed under Spectralight. Subjects fixated on 11 Munsell hues mounted on white cards and matched their afterimages with chips from the Munsell Book of Color. Samples were drawn from 125 participants in two groups, one practiced, the other unfamiliar with afterimage. No single afterimage or Munsell color chip was reported for any of the stimulus hues. However, most afterimage responses for nine stimulus colors fell within one Munsell hue family. Afterimages reported for the remaining two stimulus colors of purple-blue and yellow-red span two adjacent hue families. Results suggest new alternatives to traditional subtractive color complements. New afterimage opposites are provided.

Studies on the possible chemical, immunochemical and morphological differences at the cell surfaces of immunosensitive and immunoresistant, Moloney virus-induced, lymphoma cell-lines.

Comparison was made of several cell-surface parameters in the immunosensitive, Moloney virus-induced, mouse lymphoma, YAC, and its immunoresistant variant, YACIR. The characteristics of the two cell lines appeared to be similar by most of the criteria employed. The poly(acrylamide)-gel electrophoresis (with sodium dodecyl sulfate) patterns, after staining with Coomassie Brilliant Blue, of detergent-solubilized materials, appeared to be identical. After elution from a gel filtration column, no major differences were observed in the protein profiles of material cleaved from viable cells by proteolysis. Scanning and transmission electron microscopy revealed no major differences between the YAC and YACIR cells. The concentration of the lectins, Ricinus communis agglutinin, concanavalin A, wheat-germ agglutinin, and Solanum tuberosum (potato) agglutinin, required to agglutinate viable cells of the two lines were not significantly different. Neither cell was agglutinated by the lectins from Dolichos biflorus or Vicia graminea. Significant differences were, however, observed in the concentrations of lectin from Arachis hypogaea (peanut) needed to agglutinate the two cells. Although similar amounts (184-188 micrograms/10(9) cells) of sialic acid were released from viable cells by neuraminidase (V. cholerae), striking differences were observed in the composition of this material: 48% of N-glycolylneuraminic acid for YAC and 15% for YACIR. The remainder was N-acetylneuraminic acid for each cell line.