Evaluating the fitness of human lysozyme transgenic dairy goats: growth and reproductive traits

While there are many reports in the literature describing the attributes of specific applications of transgenic animals for agriculture, there are relatively few studies focusing on the fitness of the transgenic animals themselves. This work was designed to gather information on genetically modified food animals to determine if the presence of a transgene can impact general animal production traits. More specifically, we used a line of transgenic dairy goats expressing human lysozyme in their mammary gland to evaluate the reproductive fitness and growth and development of these animals compared to their non-transgenic counterparts and the impact of consuming a transgenic food product, lysozyme-containing milk. In males, none of the parameters of semen quality, including semen volume and concentration, total sperm per ejaculate, sperm morphology, viability and motility, were significantly different between transgenic bucks and non-transgenic full-sib controls. Likewise, transgenic females of this line did not significantly differ in the reproductive traits of gestation length and litter size compared to their non-transgenic counterparts. To evaluate growth, transgenic and non-transgenic kid goats received colostrum and milk from either transgenic or non-transgenic does from birth until weaning. Neither the presence of the transgene nor the consumption of milk from transgenic animals significantly affected birth weight, weaning weight, overall gain and post-wean gain. These results indicate that the analyzed reproductive and growth traits were not regularly or substantially impacted by the presence or expression of the transgene. The evaluation of these general parameters is an important aspect of defining the safety of applying transgenic technology to animal agriculture

Psychometric Evaluation and Design of Patient-Centered Communication Measures for Cancer Care Settings

Objective To evaluate the psychometric properties of questions that assess patient perceptions of patient-provider communication and design measures of patient-centered communication (PCC). Methods Participants (adults with colon or rectal cancer living in North Carolina) completed a survey at 2 to 3 months post-diagnosis. The survey included 87 questions in six PCC Functions: Exchanging Information, Fostering Health Relationships, Making Decisions, Responding to Emotions, Enabling Patient Self-Management, and Managing Uncertainty. For each Function we conducted factor analyses, item response theory modeling, and tests for differential item functioning, and assessed reliability and construct validity. Results Participants included 501 respondents; 46% had a high school education or less. Reliability within each Function ranged from 0.90 to 0.96. The PCC-Ca-36 (36-question survey; reliability=0.94) and PCC-Ca-6 (6-question survey; reliability=0.92) measures differentiated between individuals with poor and good health (i.e., known-groups validity) and were highly correlated with the HINTS communication scale (i.e., convergent validity). Conclusion This study provides theory-grounded PCC measures found to be reliable and valid in colorectal cancer patients in North Carolina. Future work should evaluate measure validity over time and in other cancer populations. Practice implications The PCC-Ca-36 and PCC-Ca-6 measures may be used for surveillance, intervention research, and quality improvement initiatives

Investigating the clinical use of structured light plethysmography to assess lung function in children with neuromuscular disorders

BackgroundChildren and young people with neuromuscular disorders (NMD), such as Duchenne Muscular Dystrophy (DMD), develop progressive respiratory muscles weakness and pulmonary restriction. Pulmonary function monitoring of the decline in lung function allows for timely intervention with cough assist techniques and nocturnal non-invasive ventilation (NIV). NMD may find the measurement of lung function difficult using current techniques. Structured Light Plethysmography (SLP) has been proposed as a novel, non-contact, self-calibrating, non-invasive method of assessing lung function. The overarching aim of this study was to investigate the use of SLP as a novel method for monitoring respiratory function in children with neuromuscular disease.MethodsSLP thoraco-abdominal (TA) displacement was correlated with forced vital capacity measurements recorded by spirometry and the repeatability of the measurements with both methods examined. SLP tidal breathing parameters were investigated to assess the range and repeatability of regional right and left side TA displacement and rib cage and abdominal wall displacement.ResultsThe comparison of the FVC measured with SLP and with spirometry, while having good correlation (R = 0.78) had poor measurement agreement (95% limits of agreement: -1.2 to 1.2L) The mean relative contribution of right and left TA displacement in healthy controls was 50:50 with a narrow range. Repeatability of this measure with SLP was found to be good in healthy controls and moderate in NMD children with/without scoliosis but with a wider range. The majority of the control group displayed a predominant rib cage displacement during tidal breathing and those who displayed predominant abdominal wall displacement showed displacement of both regions close to 50:50 with similar results for the rib cage and abdomen. In comparison, children with NMD have a more variable contribution for all of these parameters. In addition, SLP was able to detect a reduction in abdominal contribution to TA displacement with age in the DMD group and detect paradoxical breathing in children with NMD. Using SLP tracings during tidal breathing we were able to identify three specific patterns of breathing amongst healthy individuals and in children with NMD.ConclusionsSLP is a novel method for measuring lung function that requires limited patient cooperation and may be especially useful in children with neuromuscular disorders. Measuring the relative contributions of the right and left chest wall and chest versus abdominal movements allows a more detailed assessment

Estimating the incidence of acute infectious intestinal disease in the community in the UK:A retrospective telephone survey

Objectives: To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design. Design/Setting: A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days. Participants: 14,813 individuals for all of whom we had a legible recording of their agreement to participate Outcomes: Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause. Results: The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135 – 2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377 – 778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time. Conclusions: The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates

Infrared Dark Clouds in the Small Magellanic Cloud?

We have applied the unsharp-masking technique to the 24 $\mu$m image of the Small Magellanic Cloud (SMC), obtained with the Spitzer Space Telescope, to search for high-extinction regions. This technique has been used to locate very dense and cold interstellar clouds in the Galaxy, particularly infrared dark clouds (IRDCs). Fifty five candidate regions of high-extinction, namely high-contrast regions (HCRs), have been identified from the generated decremental contrast image of the SMC. Most HCRs are located in the southern bar region and mainly distributed in the outskirts of CO clouds, but most likely contain a significant amount of H2. HCRs have a peak-contrast at 24 $\mu$m of 2 - 2.5 % and a size of 8 - 14 pc. This corresponds to the size of typical and large Galactic IRDCs, but Galactic IRDCs are 2 - 3 times darker at 24 $\mu$m than our HCRs. To constrain the physical properties of the HCRs, we have performed NH3, N2H+, HNC, HCO+, and HCN observations toward one of the HCRs, HCR LIRS36-EAST, using the Australia Telescope Compact Array and the Mopra single-dish radio telescope. We did not detect any molecular line emission, however, our upper limits to the column densities of molecular species suggest that HCRs are most likely moderately dense with n ~ 10^{3} cm-3. This volume density is in agreement with predictions for the cool atomic phase in low metallicity environments. We suggest that HCRs may be tracing clouds at the transition from atomic to molecule-dominated medium, and could be a powerful way to study early stages of gas condensation in low metallicity galaxies. Alternatively, if made up of dense molecular clumps < 0.5 pc in size, HCRs could be counterparts of Galactic IRDCs, and/or regions with highly unusual abundance of very small dust grains.Comment: accepted for publication in the Astronomical Journa

Dietary Docosahexaenoic Acid Prevents Silica-Induced Development of Pulmonary Ectopic Germinal Centers and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse

Ectopic lymphoid structures (ELS) consist of B-cell and T-cell aggregates that are initiated de novo in inflamed tissues outside of secondary lymphoid organs. When organized within follicular dendritic cell (FDC) networks, ELS contain functional germinal centers that can yield autoantibody-secreting plasma cells and promote autoimmune disease. Intranasal instillation of lupus-prone mice with crystalline silica (cSiO2), a respirable particle linked to human lupus, triggers ELS formation in the lung, systemic autoantibodies, and early onset of glomerulonephritis. Here we tested the hypothesis that consumption of docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid with anti-inflammatory properties, influences the temporal profile of cSiO2-induced pulmonary ectopic germinal center formation and development of glomerulonephritis. Female NZBWF1 mice (6-wk old) were fed purified isocaloric diets supplemented with 0, 4, or 10 g/kg DHA - calorically equivalent to 0, 2, or 5 g DHA per day consumption by humans, respectively. Beginning at age 8 wk, mice were intranasally instilled with 1 mg cSiO2, or saline vehicle alone, once per wk, for 4 wk. Cohorts were sacrificed 1, 5, 9, or 13 wk post-instillation (PI) of the last cSiO2 dose, and lung and kidney lesions were investigated by histopathology. Tissue fatty acid analyses confirmed uniform dose-dependent DHA incorporation across all cohorts. As early as 1 wk PI, inflammation comprising of B (CD45R+) and T (CD3+) cell accumulation was observed in lungs of cSiO2-treated mice compared to vehicle controls; these responses intensified over time. Marked follicular dendritic cell (FDC; CD21+/CD35+) networking appeared at 9 and 13 wk PI. IgG+ plasma cells suggestive of mature germinal centers were evident at 13 wk. DHA supplementation dramatically suppressed cSiO2-triggered B-cell, T-cell, FDC, and IgG+ plasma cell appearance in the lungs as well as anti-dsDNA IgG in bronchial lavage fluid and plasma over the course of the experiment. cSiO2 induced glomerulonephritis with concomitant B-cell accumulation in the renal cortex at 13 wk PI but this response was abrogated by DHA feeding. Taken together, realistic dietary DHA supplementation prevented initiation and/or progression of ectopic lymphoid neogenesis, germinal center development, systemic autoantibody elevation, and resultant glomerulonephritis in this unique preclinical model of environment-triggered lupus

Acute Responses in Agonists of uEGF to Moderate-Intensity and High-Intensity Interval Exercise in Mid-Spectrum CKD

Urine epidermal growth factor (uEGF) is a novel biomarker utilized in assessing renal health in various renal diseases, specifically chronic kidney disease (CKD). uEGF promotes multiple intracellular pathways, stimulating renal cell growth, survival, and replication. uEGF production is activated by multiple agonists that bind to the uEGF receptor. Aerobic exercise initiates the upregulation of several of these agonists to increase the production of uEGF. Depending on the mode and intensity of aerobic exercise, uEGF agonists may activate differently in CKD populations. PURPOSE: To determine the influence of an acute bout of steady-state exercise (SSE) and high-intensity interval exercise (HIIE) on concentrations of uEGF agonists (serum insulin-like growth factor 1 (IGF-1), angiotensin II receptor type 1 (AGTR-1), and transforming growth factor beta 1 (TGF-β1)) in mid-spectrum CKD. METHODS: Twenty participants (n = 6 men; n = 14 women; age 62.0 + 9.9 yr; weight 80.9 + 16.2 kg; body fat 37.3 + 8.5% of weight; VO2max 19.4 + 4.7 ml/kg/min) completed 30 min of SSE at 65% VO2reserve or HIIE by treadmill walking (90% and 20% of VO2reserve in 3:2 min ratio) in a randomized crossover design. Both exercise conditions averaged ~ 65% VO2reserve. Blood and urine samples were obtained under standardized conditions just before, 1hr, and 24hrs after exercise. uEGF (ng/mL), serum IGF-1 (ng/mL), AGTR-1 (ng/mL), and TGF-β1 (pg/mL) responses were analyzed using 2 (condition) by 3 (sample point) repeated measures ANOVAs and Pearson Correlations. RESULTS: Serum IGF-1 and AGTR-1 increased 1hr and 24hr post-exercise in both exercise conditions; however, statistical significance was not achieved (p = 0.28 and p = 0.09). Similarly, serum TGF-β1 decreased at 24hrs in both exercise conditions but statistically remained unaltered (p = 0.42). IGF-1 was significantly correlated to uEGF in both conditions at all three-time points (p = 0.03), while AGTR-1 was significantly correlated to uEGF at 1hr in HIIE. uEGF findings were previously reported in ACSM abstract (DOI: 10.1249/01.mss.0000560710.72569.11). CONCLUSION: Agonists of uEGF remained unaltered following an acute bout of SSE and HIIE in mid-spectrum CKD. Further research is needed to understand better uEGF response activation to aerobic exercise in mid-spectrum CKD

An Inventory and Assessment of Sample Sources for Survey Research with Agricultural Producers in the U.S.

Researchers need probability samples to collect representative survey data about the behaviors and attitudes of agricultural producers they study in relation to the natural resources that they manage, yet obtaining accurate and complete sampling frames is challenging. We extract data from a publication database to identify the most commonly used sampling frame sources in survey research of agricultural producers in the U.S., finding that government program participant lists are used most often, while private vendor samples are increasingly being purchased. Based on our research experience, we find that for many projects, private vendors can provide the most rigorous samples. Given that survey methods remain a useful and popular method for studying the behaviors and attitudes of producers on a variety of topics, such an assessment and guide is needed for researchers and practitioners

Eliciting the child's voice in adverse event reporting in oncology trials: Cognitive interview findings from the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events initiative: Reeve et al.

Adverse event (AE) reporting in oncology trials is required, but current practice does not directly integrate the child’s voice. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being developed to assess symptomatic AEs via child/adolescent self-report or proxy-report. This qualitative study evaluates the child’s/adolescent’s understanding and ability to provide valid responses to the PRO-CTCAE to inform questionnaire refinements and confirm content validity