BACKGROUND:To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases.METHODS:A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed.RESULTS:Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1Gy and 24.7Gy for the SC and CC plans (p<0.0001). The volume of contralateral parotid receiving 40Gy or more was respectively 5.3% and 18.2% (p<0.0001)CONCLUSION:Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage.

BACKGROUND:In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed.METHODS:A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70Gy (62.4-75Gy).RESULTS:At a median follow-up of 14months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications.CONCLUSIONS:IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.

L’expansion et l’intensification agricole ont d’énormes conséquences sur la biodiversité. L’étude des compromis entre production et biodiversité peut aider au ciblage de mesures en faveur de la biodiversité.L’objectif de la thèse était de révéler des stratégies d’utilisation des sols agricoles qui permettraient d’enrayer le déclin des oiseaux agricoles tout en maintenant la production dans un territoire partagé entre grandes cultures et élevage de ruminants.Notre travail s’est basé sur l’étude de corrélations entre des variables décrivant l’utilisation des sols agricoles, la production agricole et plusieurs descripteurs des communautés d’oiseaux dans les milieux agricoles français.Nous avons observé des communautés d’oiseaux très spécialisées et pauvres en espèces dans les régions à haute production végétale ; et des communautés dominées par des oiseaux généralistes dans les régions à haute production animale. La stratégie qui maximise le FBI (un indice d’abondance des oiseaux agricoles) en maintenant la production dans ses composantes animale et végétale combinait une légère extensification des grandes cultures, le renforcement des régions d’élevage extensif et l’intensification des régions d’élevage déjà intensives.Nos résultats soulignent la nécessité d’adopter des solutions différenciées à la production animale et à la production végétale, au-delà de la dichotomie land sparing/land sharing. / Agricultural expansion and intensification have disastrous consequences on biodiversity. Studying the relationship between biodiversity and food production can help devise appropriate measures.The objective of this work was to reveal land use strategies to halt the decline of farmland birds while maintaining agricultural production.Our work was based on the study of correlations between agricultural land use, food production, and various bird community descriptors across French agroecosystems.In high crop production regions, we observed low-diversity communities dominated by few arable specialist species. In high livestock production regions, we observed communities dominated by generalist bird species. The land-use strategy that maximized the Farmland Bird Index under crop and livestock production constraints involved a decrease of crop intensity in the most intensive crop regions and an increase of livestock intensity in the most intensive livestock regions. Extensive livestock production was reinforced in current extensive areas.Our results have shown that different strategies are needed in crop-dominated and in livestock dominated regions.

Male Fischer rats (n=43) were used in a diet-diet/ exercise design to investigate the apparent protein sparing effects of exercise. The animals were divided into five groups: INITIAL (baseline), SEDENTARY (control), DIET, DIET/EXERCISE, and EXERCISE. Carcasses were analyzed for body composition, the blood for plasma alanine concentration and the urine for urea nitrogen concentration. The results showed no significant differences between groups in urinary urea nitrogen, plasma alanine, body weight, or carcass weights. The EXERCISE group had a significant increase in percent protein and a significant decrease in percent fat and grams of fat when compared to all other groups (p <.05).

Livestock provide as much as one-third of all protein consumed by humans, but have a disproportionate and growing environmental impact. Livestock production occupies 50-75% of agricultural land, contributes 15% of anthropogenic greenhouse gas emissions, and drives agricultural expansion in the tropics through the global trade in animal feed. This thesis therefore evaluates two strategies for shrinking the environmental impact of the livestock sector. First, I evaluate the potential for food losses (i.e. foods which were intended for human consumption, but which ultimately are not directly eaten by people) to replace grain- and soybean-based pig feeds in Europe. While food losses have been included in animal feed for millennia, the practice is all but banned in the European Union, because of disease control concerns. Several East Asian states have in the last 20 years, however, introduced regulated systems for safely recycling food losses into animal feed. I combine data from multiple sources (including government reports, the animal science literature, and factory-floor data from South Korean swill-feed factories), and find that the introduction of East Asian practices for recycling food losses as animal feed could reduce the land use of EU pork (20% of world production) by one fifth, potentially saving 1.8 million hectares of agricultural land. This would also reduce 12/14 other assessed environmental impacts and deliver economic savings for pig farmers, as swill (cooked food losses) costs 40-60% less than conventional grain-based feeds. In a survey of pig farmers (n=82) and other agricultural stakeholders (n=81) at a UK agricultural trade fair, we found high support (>75%) for the relegalisation of swill. Support for swill feeding arose in part because respondents thought that swill would lower costs, increase profitability, and be better for the environment. Our results also confirmed the critical importance of disease control and consumer communication when considering relegalisation, as respondents who thought that swill would increase disease risks and be unpalatable to consumers were less supportive of relegalisation. Any new system for the use of swill will require careful design of regulation to ensure that heat-treatment is sufficient, and to reduce to a negligible level the risk of uncooked animal by-products entering feed. Our results suggest, however, that if such a system can be established, there would be multiple benefits and widespread support for its relegalisation. Second, I evaluated the potential to increase the productivity of cattle ranching in the Brazilian Amazon. While high hopes have been placed on the potential for intensification of low-productivity cattle ranching to spare land for other agricultural uses, cattle productivity in the Amazon biome (29% of the Brazilian cattle herd) remains stubbornly low, and it is not clear how to realize theoretical productivity gains in practice. I therefore (a) surveyed six on-the-ground initiatives which have been working with local farmers to improve cattle ranching, quantifying their farm practices, animal performance, and economic results; and (b) analysed the progress that has already been made in reconciling agriculture and forest conservation, by evaluating the impact of the flagship anti-deforestation policy, the priority list (Municípios Prioritários). The survey showed that cattle intensification initiatives operating in four states have used a wide range of technologies to improve productivity by 30-490%, while supporting compliance with the Brazilian Forest Code. Using two complementary difference-in-difference estimators, I then found no evidence for trade-offs between agriculture and forest conservation under the priority list; instead, reductions in deforestation in priority list municipalities were paired with increases in cattle production and productivity (cattle/hectare). The policy had no effect on dairy or crop production. Together, these results provide real-world evidence that increases in cattle production in Brazil do not need to come at the expense of the country’s remaining native vegetation.

Cobia (Rachycentron canadum) aquaculture is poised for expansion, due in part to rapid growth rate, tolerance of culture conditions, and high market value of this species. Similar to other carnivorous marine fishes, the high monetary cost and long-range unsustainability of reliance on fish oil as the principle lipid source for cobia feeds necessitates evaluation of alternative lipid sources to spare or replace fish oil. Unfortunately, alternative lipid-based feeds may affect production performance, and typically yield fillets with reduced levels of long-chain polyunsaturated fatty acids (LC-PUFAs) such as docosahexaenoic acid (DHA, 22:6n-3). Recent research has indicated that diets rich in saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs), coupled with the application of so-called "finishing feeds" (feeds containing elevated levels of fish oil relative to grow-out feeds) at the end of the production cycle, may limit or attenuate these effects of fish oil sparing. Accordingly, I conducted two trials to evaluate the usefulness of alternative lipids and finishing in cobia culture. In the first trial, I assessed growth performance and tissue fatty acid composition of juvenile cobia fed diets (~11% lipid, ~48% protein) containing fish oil (control), or 50/50 blends of fish oil and alternative lipids (beef tallow, pork lard, partially and fully hydrogenated soy oils, and traditional soy oil) supplemented with an algal meal (to meet the 22:6n-3 requirement of cobia) for 8 weeks. Although minor differences were observed in feed intake, growth performance was otherwise equivalent among the dietary groups. Tissue fatty acid composition varied significantly among treatments, however, with alternative lipids containing higher levels of saturated (SFAs) and monounsaturated fatty acids (MUFAs) yielding tissue profiles that were most similar to those associated with the fish oil-based control feed. Although beef tallow and hydrogenated soybean oil were largely equivalent in terms of growth performance and fatty acid profile change, beef tallow was selected for further evaluation because of its low cost. In the second trial, beef tallow replaced fish oil in feeds at one of four substitution levels: 0% (100% fish oil), 33%, 67%, or 100% tallow (with algal 22:6n-3 meal included in all feeds as before). Juvenile cobia were raised on these feeds for 8 weeks, then switched to the 100% fish oil-based control feed for an 8-week finishing period. During finishing, subsamples of fish were collected every 2 weeks to quantify changes in tissue fatty acid profile over time as a result of finishing. In the second trial, the overall similarity of tissue fatty profiles to those in the 100% fish oil control treatment increased over the course of finishing, mostly as a result of declines in SFAs and MUFAs. These results suggest that SFA and MUFA-rich lipids, such as fully hydrogenated soy oil and beef tallow, are effective and strategically valuable as partial substitutes for fish oil in cobia feeds, and that finishing is at least partially effective in restoring cobia tissue fatty acid composition to a state approximating that of cobia fed only fish oil as dietary lipid.

In recent years, there has been a growing interest in feeding phytogenic products to poultry for their growth and health benefits. The objective of this experiment was to determine the effects of a phytogenic feed additive on turkey poult performance and digestive physiology over a 6-week brooding period. In total, 864 male Hybrid Converter turkey poults were obtained from a local commercial hatchery on day-of-hatch and placed into floor pens with clean pine shavings. The treatments were randomly assigned including an industry-type corn-soybean meal positive control (PC), a similar diet with a 1.5% reduction in crude protein and key amino acids (NC), or the NC with the addition of Digestarom® (PFA) included at a rate of 1 g/kg. Body weight gain (BWG), feed intake (FI), feed efficiency (FE), and mortality were recorded throughout the experiment. On day 14 poults fed the PFA had significantly higher BWG compared to the PC and NC fed birds. By day 42 birds fed the PC and PFA diets had significantly higher BWG compared to the NC, and the PC had significantly higher FE compared to the NC and PFA fed birds. No differences in FI or mortality were observed throughout the experiment. There were no significant differences in AMEn, crude protein digestibility, or nutrient transporter or pancreatic enzyme mRNA expression among treatments. However, aminopeptidase activity tended to be lower in the ileum of poults fed the PC or PFA diets compared to the NC, suggesting that the PFA may be improving protein utilization. / Master of Science / Recent regulations and customer demand have severely restricted the use of antibiotics in poultry production. Historically, antibiotics have been included in poultry diets at sub-therapeutic concentrations to improve performance and reduce disease incidence. Since this restriction, producers have experienced increased feed conversion ratio, decreased body weights, and increases in morbidity and mortality. Not only does this present an animal welfare issue, but producers experience decreased profits due to the decrease in performance associated with restricted antibiotic use. Many researchers are investigating the ability of alternative feed additives to help mitigate the lost performance this restriction has caused. One such alternative is a class of compounds known generally as phytogenic feed additives. These are herbs, spices, and associated products which can be included into the diet at relatively low concentrations. Previous research has demonstrated the ability of phytogenic feed additives to positively influence performance and gastrointestinal tract health, primarily in broiler chickens. Therefore, the objective of this thesis is to investigate the effect of a commercially available phytogenic feed additive on the performance, nutrient digestibility, and absorption in turkey poults over the first six weeks of feeding. Previous indications with this product seem to indicate that it also increases protein utilization so this product was evaluated using a reduced protein diet. By day 14, poults fed the feed additive had significantly higher body weights compared to both the positive and negative control. At the conclusion of the experiment on day 42, the birds fed the feed additive had significantly higher body weight compared to the negative control and were similar to the positive control. This suggests the ability of the feed additive to improve performance when dietary protein is reduced. Data from aminopeptidase activity in the ileum suggest a potential improvement in the efficiency of protein utilization, which may explain the performance improvements when poults were fed the phytogenic feed additive.

Bakgrund: Användningen av höga doser av opioider under generell anestesi är numera mycket vanligt. Biverkningar orsakade av opioider är väl känt inom anestesin och sjukvården och senare evidens tyder på att opioider även kan bidra till smärtutveckling. Av denna anledning har studier de senaste 20 åren ifrågasatt användningen av opioider och intresset för att minska opioidbehovet och utveckla opioidfria metoder för anestesi har växt. Syfte: Att beskriva opioidfri analgesi i generell anestesi, och hur detta påverkar den perioperativa smärtupplevelsen, jämfört med patienter i generell anestesi som fått traditionell smärtlindring med opioider. Metod: En litteraturöversikt med systematisk ansats. Artikelsökningen genomfördes i PubMed, Cinahl och Scopus. Resultatet sammanställdes utifrån 15 granskade artiklar med kvantitativ design. Resultat: Litteraturöversikten visar att det finns ett stort antal läkemedel som kan användas inom opioidfri anestesi, samt deras för- och nackdelar för smärtupplevelsen jämfört opioider. De protokoll som användes vid opioidbaserad anestesi eller för opioidsparande anestesi är inte standardiserade och därför är det inte möjligt att syntetisera resultatet och ställa olika metoder mot varandra i denna litteraturöversikt. De flesta artiklar visade att det går att minska intraoperativt och postoperativt opioidbehov för patienter och ändå erbjuda likvärdig smärtlindring. De patienter som fick en opioidfri eller opioidsparande anestesi hade inte en försämrad perioperativ smärtupplevelse. Den mängd metoder som beskrevs indikerar att analgesi kan anpassas efter patientens individuella förutsättningar. Slutsats: Litteraturöversikten visade att olika läkemedel och metoder kan användas för att ge analgesi till patienten vid opioidfri anestesi samt dess effekt på smärtupplevelsen kontra opioider. De flesta alternativa läkemedel som används i artiklarna gav ett mer gynnsamt eller likvärdigt utfall för patienten. Genom utveckling av fler metoder för analgesi under anestesi kan anestesin i större omfattning utgå från individens behov och förutsättningar, vilket bidrar till en mer personcentrerad vård. Litteraturöversiktens resultat visar på en stor spridning och det är därför svårt att bedöma vilka läkemedel som är bäst lämpade. Det krävs således mer forskning inom detta ämne för att möjliggöra jämförelser och utarbeta protokoll som gör opioidfri anestesi till etablerad och säker metod för patienten. / Background: High dose opioids during general anesthesia are frequently used. The side effects caused by opioids are well known in anesthesia and healthcare and recent evidence implies opioides can contribute to the development of pain. For this reason, studies over the past 20 years have questioned the use of opioids and an interest has grown in reducing the need of opioids and developing opioid-free methods for anesthesia. Aim: To describe opioid-free analgesia in general anesthesia, and how this affects the perioperative pain experience, compared to patients in general anesthesia who have received traditional opioid-based pain relief. Method: A literature study with systematic approach. The article search was performed in PubMed, Cinahl and Scopus. The result was compiled based on 15 reviewed articles with quantitative design. Result: The literature review shows that there are a large number of drugs that can be used in opioid-free anesthesia and the advantages and disadvantages of these drugs versus opioids. The protocols used for opioid-based anesthesia or for opioid-saving anesthesia are not standardized and therefore it is not possible to synthesize the results or set different methods against each other in this review. Most articles found that it is possible to reduce the intraoperative and postoperative need of opioid for patients and still offer equivalent pain relief. The patients receiving opioid-free or opioid-sparing anesthesia did not suffer a worsened pain-related experience. The amount of methods described indicates that the analgesia can be customized accordingly to the patient's individual circumstances. Conclusion: The literature review described various drugs and methods that can be used to give analgesia to the patient during opioid-free anesthesia and the effect on the pain-related experience. Most of the alternative drugs used in the articles gave a more favorable or equivalent outcome for the patient. By developing more methods for analgesia during anesthesia, it is in a greater extent possible to adjust the anesthesia depending on the individuals needs, which contributes to a more person-centered care. The result shows a wide spread and it is therefore difficult to assess which drugs are best suited. Thus, more research is required in this subject to prepare protocols that make opioid-free anesthesia an established and safe method for the patient.

Opioids, such as oxycodone, morphine, and fentanyl, are commonly used medications in the treatment of moderate to severe pain. In spite of their efficacious analgesic properties, their increased prescribing rates by physicians and inherent abuse-related effects have led to the ongoing opioid epidemic. Their clinical utility is limited by the risk of adverse dose-dependent side effects, such as constipation and respiratory depression, and the development of tolerance and dependence. Opioid-sparing adjunctive therapies are sought to address these issues by reducing the dose of opioid needed to achieve analgesia through alternative non-opioidergic mechanisms and as a result, reduce the incidence of the previously mentioned side effects. Serotonin type-2C receptor agonists have demonstrated antinociceptive efficacy in preclinical models of chronic pain. Lorcaserin is a selective 5-HT2C receptor agonist and was reported to attenuate the abuse-related effects of oxycodone. The antinociceptive properties of 5-HT2C receptor agonists and their potential to alter the abuse-related effects of commonly abused drugs suggest that lorcaserin may be a potential opioid-sparing therapeutic. The goal of these studies was to evaluate the utility of lorcaserin, in combination with opioids, in a preclinical model of acute pain. Based on previous studies demonstrating the antinociceptive activity of 5-HT2C agonists, the hypotheses for these studies were that lorcaserin would increase the acute antinociceptive effects of opioids and would attenuate the development of tolerance associated with chronic opioid consumption. The results demonstrate that the acute antinociceptive effects and the time-course of activity of opioids were enhanced by doses of lorcaserin. These effects were mediated through activation of the 5-HT2C receptor and were not blocked by administration of naloxone. Additionally, the acute effects of lorcaserin to increase opioid potency and time course was not mediated through changes in opioid distribution in the blood or central tissues. Opioid tolerance was evaluated in vivo, and tolerance was developed using two methods of treatment: an acute (single dose administration) model of tolerance and a multiple-injection model. Testing the effect of lorcaserin in these models was important because current research suggests that the mechanisms that underlie both models of tolerance are distinct from one another. The results demonstrate that lorcaserin significantly blocked the development of acute tolerance in the whole animal and on a single cell level in dorsal root ganglion cell cultures. In the multiple-day tolerance model, lorcaserin partially attenuated the development of opioid antinociceptive tolerance. Chronic administration of an opioid is associated with desensitization of the MOR, and the effect of lorcaserin on opioid tolerance may be mediated through changes in MOR functional activity. Upon further investigation using agonist-stimulated [35S]GTPyS, the results showed that lorcaserin altered basal binding of [35S]GTPyS but not agonist-stimulated binding in mice that received chronic opioid treatment. These data suggest that the effect of lorcaserin on opioid tolerance, in the multiple-injection model, is not mediated through changes in MOR functional activity. Collectively, the tolerance studies suggest that the effect of 5-HT2C receptor activation by lorcaserin has differential effects on the stages of opioid tolerances and further supports the notion that the mechanisms that underlie the stages of opioid tolerance are distinct. Given the efficacy of lorcaserin to increase the acute antinociceptive effects of opioids and its ability to impair the development of opioid tolerance, collectively, these data suggest that lorcaserin may be a useful opioid-sparing adjunctive therapy.

Gabapentin is an anticonvulsant that has become a treatment option for several indications that are not approved by Health Canada. Commonly, gabapentin is prescribed for neuropathic pain and anxiety disorders. The objective of this dissertation was to evaluate the efficacy of gabapentin for reducing pre-operative anxiety, post-operative pain and opioid consumption. The initial study examined regimens of pre-operative and post-operative gabapentin given to patients undergoing total knee arthroplasty. Patients that received gabapentin postoperatively used significantly less morphine at 24 hrs, 36 hrs and 48 hrs (p<0.05). Furthermore these patients had significantly better active-assisted knee flexion on postoperative day (POD) 2, POD 3, with a trend toward better flexion on POD 4. Next, we examined whether: 1) gabapentin administration reduces pain and opioid use after total hip arthroplasty using a multimodal analgesic regimen that included spinal anesthesia; and whether 2) preoperative administration of gabapentin is more effective than postoperative administration. Our results demonstrated that whether a 600 mg dose of gabapentin was given preoperatively or postoperatively, patients’ postoperative morphine consumption or pain scores were not reduced in hospital nor was there a reduction in pain 6 months after hip arthroplasty. The third study found that a single dose of 600 mg of gabapentin was not sufficient to reduce preoperative anxiety in patients prior to hip arthroplasty. In contrast, the final study demonstrated that 1200mg of gabapentin reduced pre-operative anxiety and pain catastrophizing in female patients with moderate to high levels of preoperative anxiety prior to major surgery, but also increased preoperative and early postoperative sedation. Our findings demonstrate the efficacy of perioperative gabapentin with respect to preoperative anxiety reduction and decreasing morphine consumption after surgery. Future studies that focus on the optimal dose and duration of perioperative gabapentin, with the aim of improving functional outcomes and decreasing the incidence and severity chronic post-surgical pain are warranted.