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OBJECTIVE To describe mortality trends of men and women working in various petrochemical and refinery operations of a U.S.-based company. METHODS The cohort consists of full-time employees with at least one day of service during 1979 through 2010. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for 111 possible causes of death studied. RESULTS SMRs for malignant mesothelioma and asbestosis were highest for the 1940's decade of hire. Increased SMRs were observed for malignant melanoma and motor neuron disease with no obvious work patterns. Decreasing mortality patterns were observed for aplastic anemia and acute non-lymphocytic leukemia. CONCLUSIONS Mortality surveillance of this large established cohort aids in assessing the chronic health status of the workforce. Identifying methods for incorporating job-exposure matrices and non-occupational risk factors could further enhance interpretations for some findings such as motor neuron disease.

Acute exposure to hydrogen sulfide initiates a series of hallmark biological effects that occur progressively at increasing exposure levels: odor perception, conjunctivitis, olfactory paralysis, "knockdown," pulmonary edema, and apnea. Although effects of exposure to high concentrations of hydrogen sulfide are clear, effects associated with chronic, low-level exposure in humans is under debate, leading to uncertainty in the critical effect used in regulatory risk assessments addressing low dose exposures. This study integrates experimental animal, observational epidemiology, and occupational exposure evidence by applying a pathway-based approach. A hypothesized adverse outcome pathway (AOP) network was developed from 34 studies, composed of 4 AOPs sharing 1 molecular initiating events (MIE) and culminating in 4 adverse outcomes. A comparative assessment of effect levels and weight of evidence identified an AOP leading to a biologically-plausible, low-dose outcome relative to the other outcomes (nasal lesions, 30 ppm versus olfactory paralysis,100 ppm; neurological effects,80 ppm; pulmonary edema,80 ppm). This AOP (i.e. AOP1) consists of the following key events: cytochrome oxidase inhibition (10 ppm), neuronal cell loss (30 ppm), and olfactory nasal lesions (defined as both neuronal cell loss and basal cell hyperplasia;30 ppm) in rodents. The key event relationships in this pathway were supported by moderate empirical evidence and have high biological plausibility due to known mechanistic understanding and consistency in observations for diverse chemicals.

Throughout history, environmental epidemiology has proven crucial to identify certain threats to human health and to provide a basis for the development of life-saving public health policies. However, epidemiologists are facing challenges when studying tenuous threats such as environmental exposure to chemicals, whose association with adverse health effects may be difficult to characterize. As a result, epidemiological data can seldom be fully leveraged for quantitative risk assessment and decision-making. Despite two decades of efforts to improve a more systematic integration of human data to evaluate human health risks, assessors still heavily rely on animal data to do so, while epidemiology plays more of a secondary role. Although the need for more and better collaboration between risk assessors and epidemiologists is widely recognized, both fields tend to remain siloed. In 2017, the Health and Environmental Sciences Institute initiated a project engaging the epidemiology, exposure science, and regulatory communities with tripartite representation from regulators, industry, and academia in a dialogue on the use of environmental epidemiology for regulatory decision-making. Several focus groups attended by epidemiology, exposure science, and risk assessment experts were organized to explore incentives and barriers to collaboration, to ultimately bridge the gap between the various disciplines, and to realize the full potential of epidemiological data in risk assessment. Various ideas that have emerged from these meetings could help ensure the better integration of epidemiological data in quantitative risk assessment and contribute to building confidence in a robust and science-based regulatory decision-making process.

Venom peptides are potent and selective modulators of voltage-gated ion channels that regulate neuronal function both in health and in disease. We previously identified the spider venom peptide Tap1a from the Venezuelan tarantula Theraphosa apophysis that targeted multiple voltage-gated sodium and calcium channels in visceral pain pathways and inhibited visceral mechano-sensing neurons contributing to irritable bowel syndrome. In this work, alanine scanning and domain activity analysis revealed Tap1a inhibited sodium channels by binding with nanomolar affinity to the voltage-sensor domain II utilising conserved structure-function features characteristic of spider peptides belonging to family NaSpTx1. In order to speed up the development of optimized NaV-targeting peptides with greater inhibitory potency and enhanced in vivo activity, we tested the hypothesis that incorporating residues identified from other optimized NaSpTx1 peptides into Tap1a could also optimize its potency for NaVs. Applying this approach, we designed the peptides Tap1a-OPT1 and Tap1a-OPT2 exhibiting significant increased potency for NaV1.1, NaV1.2, NaV1.3, NaV1.6 and NaV1.7 involved in several neurological disorders including acute and chronic pain, motor neuron disease and epilepsy. Tap1a-OPT1 showed increased potency for the off-target NaV1.4, while this off-target activity was absent in Tap1a-OPT2. This enhanced potency arose through a slowed off-rate mechanism. Optimized inhibition of NaV channels observed in vitro translated in vivo, with reversal of nocifensive behaviours in a murine model of NaV-mediated pain also enhanced by Tap1a-OPT. Molecular docking studies suggested that improved interactions within loops 3 and 4, and C-terminal of Tap1a-OPT and the NaV channel voltage-sensor domain II were the main drivers of potency optimization. Overall, the rationally designed peptide Tap1a-OPT displayed new and refined structure-function features which are likely the major contributors to its enhanced bioactive properties observed in vivo. This work contributes to the rapid engineering and optimization of potent spider peptides multi-targeting NaV channels, and the research into novel drugs to treat neurological diseases.

Conventional spirometry produces measurement error by using repeatability criteria (RC) to discard acceptable data and terminating tests early when RC are met. These practices also implicitly assume that there is no variation across maneuvers within each test. This has implications for air pollution regulations that rely on pulmonary function tests to determine adverse effects or set standards. We perform a Monte Carlo simulation of 20,902 tests of forced expiratory volume in 1 second (FEV1), each with eight maneuvers, for an individual with empirically obtained, plausibly normal pulmonary function. Default coefficients of variation for inter‐ and intratest variability (3% and 6%, respectively) are employed. Measurement error is defined as the difference between results from the conventional protocol and an unconstrained, eight‐maneuver alternative. In the default model, average measurement error is shown to be ∼5%. The minimum difference necessary for statistical significance at p < 0.05 for a before/after comparison is shown to be 16%. Meanwhile, the U.S. Environmental Protection Agency has deemed single‐digit percentage decrements in FEV1 sufficient to justify more stringent national ambient air quality standards. Sensitivity analysis reveals that results are insensitive to intertest variability but highly sensitive to intratest variability. Halving the latter to 3% reduces measurement error by 55%. Increasing it to 9% or 12% increases measurement error by 65% or 125%, respectively. Within‐day FEV1 differences ≤5% among normal subjects are believed to be clinically insignificant. Therefore, many differences reported as statistically significant are likely to be artifactual. Reliable data are needed to estimate intratest variability for the general population, subpopulations of interest, and research samples. Sensitive subpopulations (e.g., chronic obstructive pulmonary disease or COPD patients, asthmatics, children) are likely to have higher intratest variability, making it more difficult to derive valid statistical inferences about differences observed after treatment or exposure.

The literature has shown an increased risk for mental health conditions among victims of domestic violence. Few studies have examined the relationship between mental health disorders and domestic violence among Caribbean women, and how the association might be influenced by migratory and contextual factors. This study addresses the mental well-being of U.S. Caribbean Black women victims of domestic violence, and the relationships between acculturation, discrimination, and demographic influences. An analysis of data from the 2001–2003 National Survey of American Life (NSAL) re-interview, the first and most complete study on U.S. Caribbean Blacks, was conducted. Bivariate analysis revealed an association between acts of physical domestic violence and mental health conditions, with generally higher risk among women who reported both severe physical intimate partner violence and childhood physical abuse. Multivariate logistic regression indicates an association between specific mental disorders and acts of domestic violence. Acculturation, length of residence in the United States, age, education, poverty, and country of origin were also associated with mental health. The study highlights future directions for exploration including additional investigation of the influence of acculturation on the physical health of victims of domestic violence.

Toxicology feeding studies of mineral oil hydrocarbons (MOHs), within the carbon number range C22-C28, results in species-specific epithelioid granulomas in the liver of F-344 rats but not in other rat strains, or species. While MOH has been detected, and some pathological effects have been shown to occur in other organs/tissues of F-344 rats and other rat strains/species, it is generally accepted that the effect of toxicological concern is species-specific inflammatory liver granuloma. As oil retention and other MOH-related nontoxic pathological changes in the liver are observed in humans, some have hypothesized that the potential for oil accumulation over a lifetime, through dietary sources, may predispose humans to similar liver effects as observed in F-344 rats. To address this concern, a mode of action/human relevance framework (MoA/HRF) analysis for MOH-induced epithelioid granuloma in the F-344 rat model was developed. The key events for the development of liver epithelioid granulomas were identified as increased MOH intestinal absorption, preferential tissue retention and ultimately formation of necrotic granulomas encased by infiltrating inflammatory lymphocytes. The hypothesized MoA was evaluated using the modified Bradford Hill considerations for causality and was considered to be established in the F-344 rodent model. However, key strain/species differences in the rate of intestinal absorption, tissue retention of MOH and inflammatory response to MOH in the liver were identified. Overall, the F-344 rat MoA was not considered to be relevant to humans, consistent with data showing no evidence for the formation of epithelioid granulomas with humans even in cases of massive ingestion of MOHs.

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias – as in clinical medicine and healthcare – or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work. Keywords: Methodological quality, Reporting quality, Risk of bias, Scoping review, Toxicity studies

Coccidioides immitis and Coccidioides posadasii are soil-dwelling fungi and the causative agents of coccidioidomycosis, a mycosis endemic to certain semiarid regions in the Americas. The most common route of infection is by inhalation of airborne Coccidioides arthroconidia. Once a susceptible host inhales the conidia, a transition to mature endosporulated spherules can occur within the first 5 days of infection. For this study, we examined the host response in a murine model of coccidioidomycosis during a time period of infection that has not been well characterized. We collected lung tissue and bronchoalveolar lavage fluid (BALF) from BALB/c mice that were infected with a C. immitis pure strain, a C. immitis hybrid strain, or a C. posadasii strain as well as uninfected mice. We compared the host responses to the Coccidioides strains used in this study by assessing the level of transcription of selected cytokine genes in lung tissues and characterized host and fungal proteins present in BALF. Host response varied depending on the Coccidioides strain that was used and did not appear to be overly robust. This study provides a foundation to begin to dissect the host immune response early in infection, to detect abundant Coccidioides proteins, and to develop diagnostics that target these early time points of infection.

The objective of this study was to investigate the genetic relationships between skin lesion traits in group housed growing pigs as a measure of short- (in a newly mixed group) and long- (in a socially stable group) term aggression and commonly used commercial performance measures: growth, feed intake, feed efficiency, and carcass traits. Data on 2,413 growing pigs (138 groups) were available. Pigs were mixed into new social groups of 18 animals, and skin lesions were counted 24 h (SL24h) and 5 wk (SL5wk) postmixing. The animal model was used to estimate genetic parameters for skin lesion traits, test daily gain, lifetime daily gain, daily feed intake, feed efficiency (calculated as test daily gain divided by daily feed intake), loin depth, back fat, and HCW. Skin lesions had a heritable component, ranging from 0.08 for anterior SL24h to 0.22 for central SL5wk and would, therefore, be suitable as a method of phenotyping aggression for selection purposes. Significant positive genetic correlations were found between SL24h and SL5wk (0.46 to 0.81). Positive genetic correlations were also found between SL24h (central and posterior body regions) or SL5wk (all body regions) and the production traits lifetime daily gain, test daily gain, and HCW (0.29 to 0.54). Central SL24h, anterior SL5wk, and posterior SL5wk were found to correlate positively with feed efficiency (0.39 to 0.50), suggesting that pigs with more lesions convert feed more efficiently. Where significant, the magnitude of phenotypic correlations was low but positive (0.07 to 0.10). These results suggest that, genetically, animals that receive many lesions show improved performance compared to those with few lesions, except for anterior SL24h, which had previously been shown to be genetically positively correlated with the initiation of nonreciprocal attacks. It may, therefore, be possible, via selection against anterior skin lesions at mixing, to reduce this form of 1-sided aggression without adversely affecting production traits.

Mixing of growing pigs results in aggressive contests between group members. As aggression serves to establish dominance relationships, it is possible that increased initial aggression may facilitate the formation of social hierarchies. The objective of the study was to investigate whether there is a phenotypic link between behavioural traits of aggression at mixing and increased long-term group social stability. Aggressive behavioural traits were recorded for 24 h after mixing, whereas the numbers of skin lesions (anterior, central and posterior) were obtained 24 h (SL24h) and 3 weeks post-mixing (SL3wk) for 1,166 pigs. At the group level, aggressive behavioural traits were positively correlated with anterior SL24h (0.34 to 0.67; P

Background Therapeutic mammaplasty, which combines breast reduction and mastopexy techniques with tumour excision, may extend the boundaries of breast-conserving surgery and improve outcomes for patients, but current practice is unknown and high-quality outcome data are lacking. This prospective multicentre cohort study aimed to explore the practice and short-term outcomes of the technique. Methods Consecutive patients undergoing therapeutic mammaplasty at participating centres between 1 September 2016 and 30 June 2017 were recruited to the study. Demographic, preoperative, operative, oncological and complication data were collected. The primary outcome was unplanned reoperation for complications within 30 days of surgery. Secondary outcomes included re-excision rates and time to adjuvant therapy. Results Overall, 880 patients underwent 899 therapeutic mammaplasty procedures at 50 centres. The most common indications were avoidance of poor cosmetic outcomes associated with standard breast-conserving surgery (702 procedures, 78·1 per cent) or avoidance of mastectomy (379, 42·2 per cent). Wise-pattern skin incisions were the most common (429 of 899, 47·7 per cent), but a range of incisions and nipple–areola pedicles were used. Immediate contralateral symmetrization was performed in one-third of cases (284 of 880, 32·3 per cent). In total, 205 patients (23·3 per cent) developed a complication, but only 25 (2·8 per cent) required reoperation. Median postoperative lesion size was 24·5 (i.q.r. 16–38) mm. Incomplete excision was seen in 132 procedures (14·7 per cent), but completion mastectomy was required for only 51 lesions (5·7 per cent). Median time to adjuvant therapy was 54 (i.q.r. 42–66) days. Conclusion Therapeutic mammaplasty is a safe and effective alternative to mastectomy or standard breast-conserving surgery. Further work is required to explore the impact of the technique on quality of life, and to establish cost-effectiveness.

The effects of exposure to high concentrations of hydrogen sulfide (H2S) on human health are well known. However, the potential human health hazards posed by low-level chronic environmental H2S exposure are being debated. Accordingly, we reviewed the literature regarding the effects of chronic, environmentally-relevant H2S exposures on human health. All human observational studies using an analytical study design (e.g. cohort, cross-sectional, case-control) to evaluate chronic-duration low-level H2S exposure (approximately ≤ 10 ppm on average, for 1 year or more), were evaluated for a range of health outcomes. Respiratory symptoms in both adults and children were the most consistently reported symptoms on the increase. When reported, such effects appear to be temporary, given that there is no consistent evidence of pulmonary function deficit in either age group, among those chronically exposed to low H2S concentrations. While sparse, some data also suggest potential ocular symptoms and disorders associated with chronic ambient level H2S exposure in adults (not children), but the limited data on H2S exposures, co-exposures and/or strong odor stimulus of H2S, temper interpretation. Neurological symptoms and deficits have been reported in some studies, but the highest quality evidence, obtained using objective outcome measures and a reasonably detailed assessment of exposure, does not support a neurological-related risk in adults (only one study in children). For the other endpoints assessed (cardiovascular, reproductive and developmental, and carcinogenicity), the results were mixed and/or conflicting, but did not indicate a potential health hazard, although this literature has several major limitations, particularly with regard to exposure estimation and the ability to assess exposure-response.

Most Borrelia species that cause tick-borne relapsing fever utilize rodents as their natural reservoirs, and for decades laboratory-bred rodents have served as informative experimental models for the disease. However, while there has much progress in understanding the pathogenetic mechanisms, including antigenic variation, of the pathogen, the host side of the equation has been neglected. Using different approaches, we studied, in immunocompetent inbred mice, the dynamics of infection with and host responses to North American relapsing fever agent B. hermsii. The spirochete’s generation time in blood of infected mice was between 4–5 h and, after a delay, was matched in rate by the increase of specific agglutinating antibodies in response to the infection. After initiating serotype cells were cleared by antibodies, the surviving spirochetes were a different serotype and, as a population, grew more slowly. The retardation was attributable to the host response and not an inherently slower growth rate. The innate responses at infection peak and immediate aftermath were characterized by elevations of both pro-inflammatory and anti-inflammatory cytokines and chemokines. Immunodeficient mice had higher spirochete burdens and severe anemia, which was accounted for by aggregation of erythrocytes by spirochetes and their partially reversible sequestration in greatly enlarged spleens and elsewhere.

Aggression at regrouping is a common issue in pig farming. Skin lesions are genetically and phenotypically correlated with aggression and have been shown to have a significant heritable component. This study predicts the magnitude of reduction in complex aggressive behavioural traits when using lesion numbers on different body regions at two different time points as selection criteria, to identify the optimum skin lesion trait for selection purposes. In total, 1146 pigs were mixed into new social groups, and skin lesions were counted 24 h (SL24h) and 3 weeks (SL3wk) post-mixing, on the anterior, centre and posterior regions of the body. An animal model was used to estimate genetic parameters for skin lesion traits and 14 aggressive behavioural traits. Estimated breeding values (EBVs) and phenotypic values were scaled and standardised to allow direct comparison across multiple traits. Individuals with SL24h and SL3wk EBVs in the least aggressive 10% of the population were compared with the population mean to predict the expected genetic and phenotypic response in aggressive behaviour to selection. At mixing, selection for low anterior lesions was predicted to affect substantially more behavioural traits of aggressiveness than lesions obtained on other body parts, with EBVs between −0.21 and −1.17 SD below the population mean. Individuals with low central SL24h EBVs also had low EBVs for aggressive traits (−0.33 to −0.55). Individuals with high SL3wk EBVs had low EBVs for aggression at mixing (between −0.24 and −0.53 SD below the population mean), although this was predicted to affect fewer traits than selection against SL24h. These results suggest that selection against anterior SL24h would result in the greatest genetic and phenotypic reduction in aggressive behaviour recorded at mixing. Selection for increased SL3wk was predicted to reduce aggression at mixing; however, current understanding about aggressive behaviour under stable social conditions is insufficient to recommend using this trait for selection purposes.

Aim The outcome of surgery for colorectal cancer in each unit in the UK is collated by the National Bowel Cancer Audit Project (NBOCAP). In 2008–2009 our unit had a raw 30-day postoperative mortality close to the national average, but when it was nationally adjusted it appeared to be an outlier. The purpose of this study was to identify reasons for this disparity. Method All records were obtained for patients undergoing surgery for colorectal cancer over the 2 years. Data submitted to NBOCAP to determine adjusted rates were compared with actual data. Results There were major discordances between submitted and actual data for American Society of Anesthesiology grades and timing of surgery. This explained why the unit appeared to be an outlier. Conclusion There is increasing emphasis on outcome of health service delivery, which has important implications. Submission of correct data is essential if objective comparison is to be made on which to base decisions on service delivery among units and within health regions.

The aim of designing and fabricating the surgical templates was to assist the surgical component of premolar transplantation, by establishing and replicating the root dimensions of the donor premolar tooth. The correct template could be used to assess the socket preparation (width and depth) prior to placement of the transplant in the recipient site, obviating the need to repeatedly try the donor tooth for fit at the recipient site, thereby minimising trauma to the periodontal ligament of the donor tooth. Seventy-five mandibular premolars and 50 maxillary second premolars were selected with varying stages of root development. All teeth had been extracted for orthodontic reasons. The root was measured for its length (maxL) and maximum (maxW) and minimum width (minW) with digital callipers from standardised reference points. These measurements were then used in the design of premolar transplant templates. The mean measurements for second maxillary premolars were maxL 14.6 mm (± 1.7), maxW 8.3 mm (± 0.5) and minW 4.9 (± 0.3). The mean measurements for mandibular premolars were maxL 14.8 (± 1.6), maxW 7.4 (± 0.6) and minW 5.3 (± 0.5). From these measurements, a range of maxillary second premolar and mandibular premolar templates have been fabricated. These figures also inform the multidisciplinary planning process for the space requirements at the donor site prior to transplantation.

Inhalation bioassays in mice and rats exposed to naphthalene (NA) show incidences of lung and nasal cancer, respectively. This paper describes a preliminary mode of action (MOA)/human relevance (HR) framework for NA. Species differences in both carcinogenic and cytotoxic responses between the rodent and human have been noted based on qualitative and quantitative differences in metabolism. Some occur at the initial oxidation of NA in the rat through CYP2F, versus CYP2A13 metabolism in the human respiratory system and which results in a difference in the specific naphthoquinone formed. Normally, subsequent reactive metabolites are then conjugated through glutathione, but high dose exposures, as in the rat bioassay, result in glutathione depletion, and the availability of 1,2-naphthoquinone for other conjugation. In the rat nose, it is proposed that a naphthoquinone imine is formed via a species and site-specific aryl amidase acting on an amino acid conjugate of the quinone. Such a quinone imine is believed to be the active agent in Alachlor and phenacetin, resulting in the same profile of respiratory tumors in the rat as NA. Based on the MOA and the limited epidemiological data indicating no human evidence of nasal or lung tumor risk, the carcinogenic response observed in rats does not appear relevant to the human.

Bioassays in mice and rats exposed via inhalation to naphthalene show incidences of lung and nasal cancer, respectively. To address the question of human relevancy, a literature search for cancer case reports in workers exposed to naphthalene was performed, along with an evaluation of major studies from industries with naphthalene-containing streams having the highest naphthalene exposures and/or most extensive epidemiology data. Although no epidemiologic studies of workers exposed solely to naphthalene were found, a population-based case-control study of oral and oropharynx cancer found no relation with naphthalene exposure. Limited case reports of laryngeal and colorectal cancer and naphthalene exposure exist, but these data are inadequate for evaluating human cancer risk. No case reports of nasal tumors were found, which is informative because case reports have historically identified several occupational carcinogens. Combined with anatomic and metabolic differences between rodent and human upper airways and data suggesting that cancer potency based on the rat bioassay is overestimated, relevancy of rat nasal tumors to humans is questionable. For lung cancer, existing human studies are insufficient to make firm conclusions about the presence or absence of a potential naphthalene-related risk, although no occupationally-related lung cancer risks were identified in the industries evaluated.

Diagnosis of mediastinal/hilar lymph nodes and peribronchial masses | || | Conventional transbronchial fine needle aspiration (TBNA) | | B | | | √ | | | Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) | | B | | | D | | | √ | | | Therapeutic procedures for malignant disease | | Malignant airway obstruction | | 1. Endobronchial debulking of tumours | | D | | | √ | | | 2. Endobronchial electrocautery or diathermy | | D | | | √ |

This study examined the genetic and phenotypic associations between finisher performance, pre-breeding body condition of the gilt, subsequent lactation feed intake and survival of the primiparous sow to farrow in the second parity. Complete data were available on ~2200 sows, along with additional cohort and historical performance data. Genetic variation was observed for average lactation feed intake (heritability: 0.18 ± 0.04), with a significant proportion of observed variation in average intake attributable to variation in lactation length. Weight and body condition (fatness) at finishing were very highly correlated genetically (0.89 ± 0.03 and 0.90 ± 0.02) and moderately correlated phenotypically (0.58 ± 0.01 and 0.58 ± 0.01) with weight and body condition before mating. Estimates of genetic (r(g)) and phenotypic (r(p)) correlations between feed intake recorded at finishing and average lactation feed intake (LADI) were moderate (r(g) = 0.26 ± 0.16 and 0.42 ± 0.22) and low (r(p) = 0.07 ± 0.02 and 0.08 ± 0.03), with r(g) dependent on the models and data subsets used for lactation intake. Non-unity genetic correlations imply that different genetic control mechanisms regulate feed intake during growth and lactation. Moderate genetic correlations between lactation feed intake with live weight (TWT) or growth rate (TADG) recorded at selection and live weight before mating (0.42 ± 0.11, 0.42 ± 0.11 and 0.37 ± 0.15) were considerably higher than the corresponding phenotypic correlations for LADI with TADG or 29WT (0.09 ± 0.02 and 0.08 ± 0.02). Correlations between fatness at selection (TFAT) or mating (29FT) and LADI were negative but not significantly different from 0. Overall, these data suggest that there is exploitable genetic variation for feed intake during lactation, and that selection is possible if lactation feed intakes are recorded. However, genetic correlations suggest that early growth seems to be related to lactation feed intake capacity. There was generally no strong evidence that selection for lean growth potential in dam lines will substantially diminish sow lactation intake capacity as a correlated response.

Evaluation of burn pain and its successful treatment has proven challenging for all staff who care for burn patients. As successful pain relief is important for full physical and psychological recovery, accurate assessment of burn pain is essential. The authors sought to prospectively evaluate two previously validated pain scales, the Critical Care Pain Observation Tool (CCPOT) and the Adult Nonverbal Scale (ANVS), in our burn population and compare them with patients' reports of pain. Both scales include nonverbal behaviors that are numerically scored and can be used in communicative as well as noncommunicative patients. Thirty-eight patients underwent 225 paired pain assessments. Assessments were compared with patients' self-reports of pain using the numeric rating scale (NRS) and the visual analog scale (VAS). Performance of the scales was evaluated by psychometric analysis. Logistic regression was used to compare pain scores with patient demographics, burn demographics, and administered analgesia. Both CCPOT and ANVS were internally consistent and able to discriminate pain intensity. However, these scales had poor interrater reliability. Furthermore, they correlated poorly with patients' self-reports of pain per the NRS and VAS pain scale scores. By logistic regression, all the pain scales showed a decrease in patient pain corresponding to the length of time after the burn. Otherwise, pain was not related to any patient demographics or evaluator experience. The size of burn was the only burn-related variable significantly associated with the pain scores, and this was only for the scores obtained with the CCPOT scale. In addition, only CCPOT and ANVS scales correlated with administered analgesia during hospitalization. The authors conclude that CCPOT and ANVS do not accurately assess pain in burn patients. However, it seems that the staff may administer analgesia based on several nonverbal clues encompassed in these scales. Future studies should address nonverbal signs of pain in burn patients. These signs could then be used in pain scales to target burn patient pain more effectively.

The management of joint replacement in lysosomal storage diseases has not been well reported. We present three patients with progressive degenerative changes of the hips who required bilateral total hip replacement in early childhood. The stature of the patients make it essential to have access to appropriately scaled prostheses. Consideration has to be given to associated disorders of the skeleton which must be carefully screened to ensure safety in providing appropriate anaesthesia as well as ensuring that there is no cardiac abnormality. In one patient, a periprosthetic fracture was sustained in one hip in the early post-operative course requiring internal fixation. The patient made a full recovery and all six hips were clinically and radiologically satisfactory at mid-term review.

Summary Background: There has been a dramatic increase in the incidence of immediate breast reconstruction after mastectomy for breast cancer over the past few decades and autologous tissue flaps are being used with increasing frequency. Concern has been expressed that these complex procedures may lead to a delay in the delivery of adjuvant therapy, which in turn may adversely affect recurrence and survival rates. Several publications have looked into the effect of immediate reconstruction on the timing of delivery of adjuvant therapy, but all types of immediate breast reconstruction (IBR) tend to be examined as a homogenous group. Aim: The aim of this review was to search current literature and look specifically at the effect of autologous tissue reconstructions on adjuvant therapy, and identify possible causes of delay. Discussion: From the data analysed, it appears that there may be a delay in the delivery of adjuvant therapy associated with autologous tissue IBR, especially transverse rectus abdominis muscle (TRAM) flaps. The studies available, however, examine small numbers of patients, which makes proving statistical significance difficult. Moreover, there also appears to be no consensus on what constitutes a delay in the delivery of adjuvant therapy. From 3% to 72% of autologous tissue IBR patients seem to receive their adjuvant treatment with a delay, according to the guidelines of the respective centres. Moreover, the period of time until chemotherapy appears generally increased from 13% to 36% compared with mastectomy alone patients. The most common reasons for delay are wound and flap complications. Conclusion: At the moment, despite the increasing popularity of autologous IBR, these procedures have not proved their oncological safety. Further studies looking at the effect of IBR, especially TRAM flap reconstruction, are needed.

A project was instigated in October 2005 to improve the end-of-life care of care home (nursing) residents across South-East Wales through coordinating the implementation of the All-Wales Integrated Care Pathway for the last days of life. One of the key areas of responsibility for the project coordinator was to evaluate the current level of palliative care knowledge and skills held by care home staff participating in the project. There are currently 112 care homes (nursing) in South-East Wales and the project has provided some level of education on end-of-life care to nursing staff from 58 (52%) of those care homes. Copyright © 2008 John Wiley & Sons, Ltd.

Traumatic injury to permanent central incisors is a common occurrence in childhood and adolescence. It is of paramount importance that expedient and appropriate care is provided to ensure an optimum short- and long-term outcome for injured teeth and, importantly, the patients themselves. Treatment planning should thus adopt a holistic approach, taking into account a number of patient- and dental-related factors. Multidisciplinary care, involving paediatric dentistry, orthodontics or oral and maxillofacial surgery may be indicated. Decisions should also be informed by a sound understanding of the exact nature and prognosis of the presenting dental injury.Poor primary management of dental trauma may have lifelong consequences for the young patient.

Community-associated methicillin-resistant Staphylococcus aureus (MRSA), particularly USA300, is a major pathogen in the outpatient setting. We suspected that USA300 had been introduced into our burn-trauma unit (BTU) when three burn patients presented with numerous simultaneous abscesses. We did molecular typing on 206 MRSA isolates from all patients on the BTU who had MRSA isolated from either nares cultures or clinical specimens obtained between April 11, 2002 and October 24, 2006. We reviewed medical records for all patients who had USA300 and for 75 control patients. Twenty-five of 206 (12.1%) patients who were colonized (n = 3) or infected (n = 22) with MRSA had USA300. Thirteen patients had abscesses drained surgically and eight had necrotizing fasciitis excised. Seven patients had burns (mean burn size 11.8 +/- 3.4%), of who four (66.7%) acquired numerous simultaneous (3-33) abscesses. Fourteen patients acquired USA300 outside of the BTU, and three acquired this strain on the BTU. Cases were more likely to have been hospitalized or to have had an operation in the 6 months before they were hospitalized than were controls (P = .001 for both). To our knowledge, this is the first study to describe numerous simultaneous MRSA abscesses in burn patients. The MRSA strain USA300 may be introduced onto burn units from the community by patients admitted with skin and soft tissue infections, especially abscesses and necrotizing fasciitis. Burn patients may be at risk for numerous abscesses with USA300, because they have open wounds and their immune systems may be compromised.

The objective of the present research was to quantify the cardiovascular and physiological responses in pigs subjected to novel alleys and ramps. Ten test subject pigs were selected per treatment. The first (trained) group were trained to navigate a course including a ramp. Testing was daily for seven days. Once training was completed, the trained and control (naive) groups were exposed to a fixed course, the course and ramp (both up and down) while heart rates, time, handling difficulty, and blood were collected to determine the innate responses. Heart rates of trained pigs were reduced significantly ( P = 0.003) compared to naive pigs travelling the same course. Both handling ease and handling time were significantly improved for the trained pigs ( P = 0.03 and P = 0.01 respectively) compared to naive pigs. Blood immune measures indicated reduced stress among trained pigs who had lower neutrophil numbers ( P = 0.04) and lower total and average phagocytosis ( P = 0.001 and P = 0.02) compared with naive pigs. This study demonstrated that the exposure of pigs to a novel environment clearly causes a mild physiological response. Pigs are not inherently stressed by alleys and ramps, but rather novel experiences cause handling problems and a stress response and minimal training can reduce the stress experience for the pig.

Limiting unwanted tooth movement, while producing desired positioning of other teeth, is a very important part of orthodontics. In this article, Benjamin Lewis outlines the concept of orthodontic anchorage, explains why it is important, and how to manipulate anchorage techniques to produce the best possible result for your patients.

The correction of dental crossbites is a common orthodontic treatment aim. This article will describe the many different types of dental crossbite as well as demonstrating a variety of different orthodontic techniques used in their correction.

Functional appliances are usually used to correct Class II malocclusions. In his second article, Benjamin Lewis describes how these appliances work and gives an overview of the many types of appliance available.

The implementation of the Caribbean Single Market and Economy (CSME) will bring, among other things, the free movement of qualified labour, which political leaders hope will give the benefits of an economic bloc to the micro-economies of the region. There is, however, the question of whether the current status quo of unequal rights and the unequal distribution of benefits for various vulnerable groups will continue. This is particularly relevant as the epidemics of HIV and AIDS deepen in the region. This commentary argues for a critical analysis of the trends now emerging in the Caribbean Single Market that may reinforce the structural vulnerabilities that act as the drivers of these epidemics.

Our teeth are constantly moved and repositioned as part of the body's natural processes; however, this does not always go smoothly. In the first article of their series, Benjamin Lewis and Nicolas Jedynakiewicz explain the uses and benefits of orthodontics for tooth correction and realignment.

Current educational literature based on experience suggests that moving pigs in small group sizes is preferred because pigs may experience less stress. This study sought to determine the optimal group size of pigs in a simulated move from home pens to a transport vehicle. Group sizes of pigs ranging from 1 to 10 pigs/group were handled through a standard handling course. During handling, cardiovascular responses, time, and handling measures were collected. Group size significantly influenced heart rate. As group size was increased, a linear increase ( P P P > 0.10) when ten pigs were moved at a time as when 5 or 6 pigs were moved at a time. Moving pigs in groups of 5 or 6 caused less ( P

The 2005 International Symposium on the evaluation of butadiene and chloroprene health risks provided the opportunity to consider the past, present and future state of research issues for 1,3-butadiene. Considerable advancements have been made in our knowledge of exposure, metabolism, biomarkers of exposure and effect, and epidemiology. Despite this, uncertainties remain which will impact the human health risk assessment for current worker and environmental exposures. This paper reviews key aspects of recent studies and the role that biomarkers of internal dosimetry can play in addressing low to high exposure, gender, and cross-species differences in butadiene toxicity and metabolism. Considerable information is now available on the detection and quantification of protein adducts formed from the mono-, di- and dihydroxy-epoxide metabolites of butadiene. The diepoxide metabolite appears to play a key role in mutagenesis. Species differences in production of this critical metabolite are reflected by the diepoxybutane-specific hemoglobin adduct, pry-Val. To date, the pry-Val adduct has not been quantifiable in human blood samples from workers with cumulative occupational exposures up to 6.3 ppm-weeks; whereas, the pry-Val was quantifiable in the blood of mice and rats with similar cumulative exposures. Levels in mice were much higher than in rats. Further improvements in analytical sensitivity for the pyr-Val adduct are on the horizon. Epidemiology studies are also described and ongoing efforts promise to help bridge our understanding of past and future risks.

ABCG2 (ATP binding cassette subfamily G, member 2) mediates resistance to a variety of cytotoxic agents. Although human ABCG2 is well characterized, the function of canine ABCG2 has not been studied previously. Feline ABCG2 has an amino acid substitution in the adenosine triphosphate-binding domain that decreases its transport capacity relative to human ABCG2. Our goal was to compare canine ABCG2-mediated chemotherapeutic drug resistance to feline ABCG2-mediated chemotherapeutic drug resistance. HEK-293 cells stably transfected with plasmid containing canine ABCG2, feline ABCG2 or no ABCG2 were exposed to carboplatin, doxorubicin, mitoxantrone, toceranib or vincristine, and cell survival was subsequently determined. Canine ABCG2 conferred a greater degree of chemotherapy resistance than feline ABCG2 for mitoxantrone. Neither canine nor feline ABCG2 conferred resistance to doxorubicin, vincristine or toceranib. Canine, but not feline, ABCG2 conferred resistance to carboplatin, a drug that is not reported to be a substrate for ABCG2 in other species.

Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated in vitro antifungal activity, with MIC 50 and MIC 90 values of 1 and 2 μg/ml, respectively, against 52 Coccidioides clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo ( P < 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment ( P < 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these in vivo results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection.