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Since its arrival in 2004, the non-native Harlequin ladybird Harmonia axyridis (Coleoptera: Coccinellidae) has rapidly spread throughout Britain, and it is now the most common coccinellid in England. There have since been concerns about the detrimental effects it may have on native coccinellids because there is a strong correlation between the arrival of H. axyridis and the decline in native species, including the two-spot ladybird, Adalia bipunctata. However, there have been few studies of the behavioural interactions between these two species, which occupy a high-niche overlap. This study investigated if the presence of H. axyridis impacts the feeding behaviour of A. bipunctata through direct competition for aphid prey. Foraging and interactive behaviour of A. bipunctata and H. axyridis were investigated within microcosms. Adalia bipuncata exhibited a similar consumption rate and time in the presence of H. axridis, yet H. axyridis consumed 3.5 times more prey items and were seven times faster compared to A. bipuncata. Observations showed that H. axyridis does not directly disrupt the feeding behaviour of A. bipunctata, but rather indirectly excludes the native species through being a superior competitor for prey items. Results indicate that the decline in native coccinellid species may be a consequence of H. axyridis competitive advantage, but that the concept of coexistence should not be dismissed.
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BACKGROUND: Physician burnout is associated with deleterious effects for physicians and their patients and might be exacerbated by practice transformation. OBJECTIVE: Assess the effect of the Comprehensive Primary Care (CPC) initiative on primary care physician experience. DESIGN: Prospective cohort study conducted with about 500 CPC and 900 matched comparison practices. Mail surveys of primary care physicians, selected using cross-sectional stratified random selection 11 months into CPC, and a longitudinal design with sample replacement 44 months into CPC. PARTICIPANTS: Primary care physicians in study practices. INTERVENTION: A multipayer primary care transformation initiative (October 2012-December 2016) that required care delivery changes and provided enhanced payment, data feedback, and learning support. MAIN MEASURES: Burnout, control over work, job satisfaction, likelihood of leaving current practice within 2 years. KEY RESULTS: More than 1000 physicians responded (over 630 of these in CPC practices) in each round (response rates 70-81%, depending on round and research group). Physician experience outcomes were similar for physicians in CPC and comparison practices. About one third of physician respondents in CPC and comparison practices reported high levels of burnout in each round (32 and 29% in 2013 [P = 0.59], and 34 and 36% in 2016 [P = 0.63]). Physicians in CPC and comparison practices reported some to moderate control over work, with an average score from 0.50 to 0.55 out of 1 in 2013 and 2016 (CPC-comparison differences of - 0.04 in 2013 [95% CI - 0.08-0.00, P = 0.07], and - 0.03 in 2016 [95% CI - 0.03-0.02, P = 0.19]). In 2016, roughly three quarters of CPC and comparison physicians were satisfied with their current job (77 and 74%, P = 0.77) and about 15% planned to leave their practice within 2 years (14 and 15%, P = 0.17). CONCLUSIONS: Despite requiring substantial practice transformation, CPC did not affect physician experience. Research should track effects of other transformation initiatives on physicians and test new ways to address burnout. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02320591.
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Esgotamento Profissional/epidemiologia , Atenção à Saúde/organização & administração , Satisfação no Emprego , Médicos de Atenção Primária/organização & administração , Atenção Primária à Saúde/tendências , Local de Trabalho/organização & administração , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Type 2 diabetes mellitus (T2DM) and obesity constitute interwoven pandemics challenging healthcare systems in developed countries, where diabetic kidney disease (DKD) is the most common cause of end-stage renal disease. Obesity accelerates renal functional decline in people with T2DM. Intentional weight loss (IWL) strategies in this population hold promise as a means of arresting DKD progression. In the present paper, we summarize the impact of IWL strategies (stratified by lifestyle intervention, medications, and metabolic surgery) on renal outcomes in obese people with DKD. We reviewed the Medline, EMBASE and Cochrane databases for relevant randomized control trials and observational studies published between August 1, 2018 and April 15, 2019. We found that IWL improves renal outcomes in the setting of DKD and obesity. Rate of progression of DKD slows with IWL, but varying outcome measures among studies makes direct comparison difficult. Furthermore, established means of estimating renal function are imperfect owing to loss of lean muscle mass with IWL strategies. The choice of optimal IWL strategy needs to be individualized; future work should establish the comparative efficacy of IWL strategies in obese people with DKD to better inform such decisions.
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Nefropatias Diabéticas , Obesidade , Redução de Peso/fisiologia , Albuminúria , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/fisiopatologia , Humanos , Estilo de Vida , Obesidade/complicações , Obesidade/terapia , Programas de Redução de PesoRESUMO
BACKGROUND: Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early-stage non-small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single-institution reports. The current multi-institutional study reported outcomes evaluating the largest such population reported to date. METHODS: Clinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan-Meier survival analyses and univariate/multivariate Cox proportional hazards models. RESULTS: A total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow-up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50-95 years) and 5.4 cm (range, 5.0-7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease-free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1-year and 2-year disease-specific survival rates were 95.5% and 78.6%, respectively. The median, 1-year, and 2-year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre-SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack-years died of radiation pneumonitis. CONCLUSIONS: The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688-696. © 2016 American Cancer Society.
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Carcinoma Pulmonar de Células não Pequenas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Resultado do TratamentoRESUMO
PURPOSE: The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM). METHODS: Established HNC quality of life questionnaires and our own MM quality of life questionnaire were sent to 15 HNC patients treated at our institution who reported using MM. Patients are clinically disease free and currently using MM to manage long-term side effects after curative HNC treatment. RESULTS: There was a 100 % response rate. Median time from treatment was 45 months (21-136 months). Most patients smoked marijuana (12 patients), while others reported ingestion (4 patients), vaporizing (3 patients), and use of homemade concentrated oil (1 patient). Six patients reported prior recreational marijuana use before diagnosis. MM provided benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasm, and sticky saliva. CONCLUSIONS: HNC patients report MM use to help with long-term side effects of radiotherapy.
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Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Maconha Medicinal/uso terapêutico , Qualidade de Vida/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Maconha Medicinal/administração & dosagem , Maconha Medicinal/farmacologia , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Despite the staggering diversity of venomous animals, there seems to be remarkable convergence in regard to the types of proteins used as toxin scaffolds. However, our understanding of this fascinating area of evolution has been hampered by the narrow taxonomical range studied, with entire groups of venomous animals remaining almost completely unstudied. One such group is centipedes, class Chilopoda, which emerged about 440 Ma and may represent the oldest terrestrial venomous lineage next to scorpions. Here, we provide the first comprehensive insight into the chilopod "venome" and its evolution, which has revealed novel and convergent toxin recruitments as well as entirely new toxin families among both high- and low molecular weight venom components. The ancient evolutionary history of centipedes is also apparent from the differences between the Scolopendromorpha and Scutigeromorpha venoms, which diverged over 430 Ma, and appear to employ substantially different venom strategies. The presence of a wide range of novel proteins and peptides in centipede venoms highlights these animals as a rich source of novel bioactive molecules. Understanding the evolutionary processes behind these ancient venom systems will not only broaden our understanding of which traits make proteins and peptides amenable to neofunctionalization but it may also aid in directing bioprospecting efforts.
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Venenos de Artrópodes/metabolismo , Artrópodes/classificação , Artrópodes/metabolismo , Evolução Molecular , Animais , Venenos de Artrópodes/genética , Genômica/métodos , Família Multigênica , FilogeniaRESUMO
Changes in agricultural practice across Europe and North America have been associated with range contractions and local extinction of bumblebees (Bombus spp.). A number of agri-environment schemes have been implemented to halt and reverse these declines, predominantly revolving around the provision of additional forage plants. Although it has been demonstrated that these schemes can attract substantial numbers of foraging bumblebees, it remains unclear to what extent they actually increase bumblebee populations. We used standardized transect walks and molecular techniques to compare the size of bumblebee populations between Higher Level Stewardship (HLS) farms implementing pollinator-friendly schemes and Entry Level Stewardship (ELS) control farms. Bumblebee abundance on the transect walks was significantly higher on HLS farms than ELS farms. Molecular analysis suggested maximum foraging ranges of 566 m for Bombus hortorum, 714 m for B. lapidarius, 363 m for B. pascuorum and 799 m for B. terrestris. Substantial differences in maximum foraging range were found within bumblebee species between farm types. Accounting for foraging range differences, B. hortorum (47 vs 13 nests/km(2) ) and B. lapidarius (45 vs 22 nests/km(2) ) were found to nest at significantly greater densities on HLS farms than ELS farms. There were no significant differences between farm type for B. terrestris (88 vs 38 nests/km(2) ) and B. pascuorum (32 vs 39 nests/km(2) ). Across all bumblebee species, HLS management had a significantly positive effect on bumblebee nest density. These results show that targeted agri-environment schemes that increase the availability of suitable forage can significantly increase the size of wild bumblebee populations.
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Agricultura/métodos , Abelhas , Conservação dos Recursos Naturais/métodos , Densidade Demográfica , Animais , Comportamento Apetitivo , Abelhas/genética , InglaterraRESUMO
Global biodiversity has suffered a decline primarily attributed to landscape simplification and intensified agricultural practices. Agricultural environments, characterized by homogeneity and frequent disturbances, are often suboptimal habitats for various insect species. While agricultural fields do favour pests, they generally fail to provide suitable habitats for natural enemies. The inclusion of diverse supporting habitats, such as semi-natural habitats, grassy and woody field margins etc. surrounding agricultural fields, play a crucial role in fostering effective biodiversity conservation. Moreover, determining the influence of different adjacent habitat types is essential in elucidating their influence on pest abundance and parasitism rates. Our two-year field study focused on assessing the abundance of Brassicogethes aeneus and its parasitism rate. The findings revealed that the adjacent habitat type did not significantly increase pest abundance and the parasitism rate of B. aeneus larvae consistently stayed over the threshold for effective biological control throughout the fields. This was attributed to the high proportion (35 and 38% in the 2 study years) of semi-natural habitats within most of the 1 km radius study areas. While our study did not identify any specific adjacent habitat type or habitat within a 1 km radius that directly impacted B. aeneus abundance, it emphasises the intricate interplay between the pests, parasitism and the surrounding environment because the interactive effect of distance from the crop edge and habitat type had a significant influence on B. aeneus infestation levels but not on parasitism. Decision tree analysis suggests that > 18% semi-natural habitat is needed to ensure sufficient levels of parasitism for effective biological control. A comprehensive understanding of habitats that influence not only B. aeneus but also other pests is critical for the successful implementation of IPM strategies and conservation initiatives within the agricultural sector.
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Besouros , Controle Biológico de Vetores , Animais , Larva , Ecossistema , BiodiversidadeRESUMO
Virtual fencing systems have emerged as a promising technology for managing the distribution of livestock in extensive grazing environments. This study provides comprehensive documentation of the learning process involving two conditional behavioral mechanisms and the documentation of efficient, effective, and safe animal training for virtual fence applications on nursing Brangus cows. Two hypotheses were examined: (1) animals would learn to avoid restricted zones by increasing their use of containment zones within a virtual fence polygon, and (2) animals would progressively receive fewer audio-electric cues over time and increasingly rely on auditory cues for behavioral modification. Data from GPS coordinates, behavioral metrics derived from the collar data, and cueing events were analyzed to evaluate these hypotheses. The results supported hypothesis 1, revealing that virtual fence activation significantly increased the time spent in containment zones and reduced time in restricted zones compared to when the virtual fence was deactivated. Concurrently, behavioral metrics mirrored these findings, with cows adjusting their daily travel distances, exploration area, and cumulative activity counts in response to the allocation of areas with different virtual fence configurations. Hypothesis 2 was also supported by the results, with a decrease in cueing events over time and increased reliance with animals on audio cueing to avert receiving the mild electric pulse. These outcomes underscore the rapid learning capabilities of groups of nursing cows in responding to virtual fence boundaries.
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Stereotactic body radiotherapy (SBRT) demonstrates excellent local control in early stage lung cancer, however a quarter of patients develop recurrence or distant metastasis. Transforming growth factor-beta (TGF-ß) supports metastasis and treatment resistance, and angiotensin receptor blockade (ARB) indirectly suppresses TGF-ß signaling. This study investigates whether patients taking ARBs while undergoing SBRT for early stage lung cancer exhibited improved overall survival (OS) or recurrence free survival (RFS) compared to patients not taking ARBs. This was a single institution retrospective analysis of 272 patients treated with SBRT for early stage lung cancer between 2009 and 2018. Patient health data was abstracted from the electronic medical record. OS and RFS were assessed using Kaplan-Meier method. Log-rank test was used to compare unadjusted survival between groups. Univariable and multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Of 247 patients analyzed, 24 (10%) patients took ARBs for the duration of radiotherapy. There was no difference in mean age, median tumor diameter, or median biologic effective dose between patients taking ARBs or not. Patients taking ARBs exhibited increased OS (ARB = 96.7 mo.; no ARB = 43.3 mo.; HR = 0.25 [95% CI: 0.10 to 0.62, P = .003]) and increased RFS (median RFS, ARB = 64.3 mo.; No ARB = 35.1 mo.; HR = 0.26 [95% CI: 0.10 to 0.63, P = .003]). These effects were not seen in patients taking angiotensin converting enzyme inhibitors (ACEIs) or statins. ARB use while undergoing SBRT for early stage lung cancer may increase OS and RFS, but ACEI use does not show the same effect.
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Produtos Biológicos , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Radiocirurgia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Produtos Biológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Receptores de Angiotensina/uso terapêutico , Estudos Retrospectivos , Fator de Crescimento Transformador beta , Fatores de Crescimento Transformadores/uso terapêutico , Resultado do TratamentoAssuntos
Dextrometorfano/efeitos adversos , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Buspirona/efeitos adversos , Clorfeniramina , Cloridrato de Duloxetina/efeitos adversos , Antagonistas dos Receptores Histamínicos H1 , Humanos , Masculino , Medicamentos Compostos contra Resfriado, Influenza e Alergia , Psicoses Induzidas por Substâncias/psicologia , Agonistas do Receptor de Serotonina/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversosRESUMO
BACKGROUND: Neonicotinoid insecticide seed treatments were withdrawn from use on cereal crops in the European Union (EU) in 2018 exposing the crops to yellow dwarf viruses transmitted by cereal aphids. To reduce prophylactic pyrethroid sprays there is a need for easier, field-specific monitoring techniques given that pest incidence is spatially and temporally highly sporadic. A field-specific monitoring method based on the use of yellow sticky traps mounted horizontally just above the crop was developed and evaluated to determine: (i) predictive capabilities of the sticky trap system, (ii) practicalities of use by farmers and agronomists, and (iii) whether landscape composition, boundary type and type of tillage affect immigration of aphid vectors. RESULTS: Yellow sticky traps effectively sampled winged cereal aphids and identified spatial differences in immigration patterns within- and between fields. Farmers and agronomist's aphid identification skills need improving, although they could detect aphid trends with minimal training. At least three times more cereal aphids were captured in crop headlands, especially next to taller field boundaries indicating that wind currents determined aphid immigration patterns within fields. Considerable between field aphid immigration was detected (24% of fields had no aphid immigration) even on the same farm. Levels of immigrating grain aphids were positively related to the proportion of grassland in the landscape. Tillage type had no impact on levels of immigrating aphids. CONCLUSION: Field-based monitoring and different management of headland areas could be used to reduce insecticide usage when controlling of cereal/barley yellow dwarf virus.
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Afídeos , Luteovirus , Animais , Produtos Agrícolas , Grão Comestível , Emigração e ImigraçãoRESUMO
OBJECTIVE: Identify a risk threshold for sudden incapacitation for safety critical positions in transportation industries supporting medical fitness for duty standards. METHODS: Systematic literature searches were performed examining acceptable risk criteria for medically related incapacitation using PubMed Central and Google Scholar databases. Websites for professional societies and national and international governmental agencies were also accessed. Article abstracts were reviewed and exhaustive searches were performed. RESULTS: International regulatory bodies have adopted definitions of acceptable risk typically with a threshold of 1% to 2% absolute risk of sudden incapacitation per annum. Several "risk-of-harm" models have been proposed that incorporate factors modulating an absolute risk constant derived from epidemiological studies. CONCLUSION: A 1% absolute annual risk of sudden incapacitation should be adopted as the threshold for determining medical fitness for duty among employees in safety critical positions in transportation industries.
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Meios de Transporte , HumanosRESUMO
OBJECTIVES: Laryngeal amyloidosis (LA) is a rare disease characterized by extracellular protein deposition within the larynx. Treatment is difficult due to the frequently submucosal and multifocal nature of disease. The mainstay of treatment is surgical resection; however, recurrence rates are high. Recently, use of radiotherapy (RT), either alone or postoperatively, for LA has been adapted from the management of extramedullary plasmacytoma and has been shown to provide local disease control. Here, we describe the experience with adjuvant RT for LA at our center. STUDY DESIGN: Retrospective case series. METHODS: Retrospective study of patients with amyloidosis of the larynx, with or without other disease sites, seen at a tertiary academic center between 2011 and 2019. Outcomes included disease characteristics, recurrence rates, treatment modalities, and pre- and posttreatment voice handicap index (VHI)-10. RESULTS: Ten patients met eligibility criteria. Mean follow-up time for all patients was 62.0 ± 41.0 months; mean follow-up time after last treatment was 51 ± 55 months. All but one patient underwent surgical resection of disease. Seven patients underwent subsequent RT. Of these seven, six underwent RT at our institution; five received a dose of 45 Gray (Gy); and one received a dose of 20 Gy. All seven completed RT without toxicity-related interruption. Patients undergoing RT underwent 2.1 ± 1.3 surgical procedures prior to RT; no patients required surgery after RT. Mean pretreatment VHI-10 was 22.9 ± 8.1; mean posttreatment VHI-10 was 12.9 ± 13.3. CONCLUSION: RT after surgery for LA can provide good local control without unacceptable toxicity and may decrease the need for further surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1810-1815, 2021.
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Amiloidose/radioterapia , Doenças da Laringe/radioterapia , Laringoscopia , Radioterapia Adjuvante/métodos , Adulto , Idoso , Amiloidose/cirurgia , Feminino , Seguimentos , Humanos , Doenças da Laringe/cirurgia , Laringe/efeitos da radiação , Laringe/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Tobacco is recognized as a causative agent for head and neck (H&N) and lung cancers, but not for cancers of the prostate or breast. Still, tobacco use during radiotherapy has been associated with poorer outcomes for all four of these commonly treated malignancies. We sought to evaluate if our providers record smoking history and discuss cessation as frequently for prostate and breast cancers as for H&N and lung cancers. METHODS: Initial consultation notes of 592 non-metastatic patients seen from January 2014 through June 2017 were reviewed using the electronic medical record. Descriptive statistics were used to evaluate smoking history and cessation discussions. The chi-squared test was used to compare frequencies. We chose two cancer sites commonly associated with tobacco use and causation (H&N and lung) and two sites not commonly associated (prostate and breast). RESULTS: Prostate cancer patients were less likely to have smoking history recorded (65%) than breast (91%), H&N (96%) or lung (97%) patients (p<0.0001). Breast and prostate cancer patients were less likely to be current smokers (10%) than H&N and lung cancer patients (29%) (p<0.0001). Smoking cessation discussions were less frequently documented in breast and prostate cancer patients (14%) than in H&N and lung cancer patients (55%) (p=0.0005). CONCLUSIONS: We document smoking history less frequently for prostate cancer patients than H&N, lung or breast cancer patients. Breast and prostate cancer patients have lower rates of current smoking than H&N and lung cancer patients. We document smoking cessation discussions less frequently in current smoking breast and prostate cancer patients than current smoking H&N and lung cancer patients. As all of these patients have been shown to experience poorer outcomes when smoking during radiotherapy, all should be asked about their smoking history.
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We would like to change the authors' names and email addresses on page 195 of paper [...].
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PURPOSE: The role of MerTK, a member of the Tyro3-Axl-MerTK family of receptor tyrosine kinase, in the immune response to radiation therapy (RT) is unclear. We investigated immune-mediated tumor control after RT in murine models of colorectal and pancreatic adenocarcinoma using MerTK wild-type and knock-out hosts and whether inhibition of MerTK signaling with warfarin could replicate MerTK knock-out phenotypes. METHODS AND MATERIALS: Wild-type and MerTK-/- BALB/c mice were grafted in the flanks with CT26 tumors and treated with computed tomography guided RT. The role of macrophages and CD8 T cells in the response to radiation were demonstrated with cell depletion studies. The role of MerTK in priming immune responses after RT alone and with agonist antibodies to the T cell costimulatory molecule OX40 was evaluated in a Panc02-SIY model antigen system. The effect of warfarin therapy on the in-field and abscopal response to RT was demonstrated in murine models of colorectal adenocarcinoma. The association between warfarin and progression-free survival for patients treated with SABR for early-stage non-small cell lung cancer was evaluated in a multi-institutional retrospective study. RESULTS: MerTK-/- hosts had better tumor control after RT compared with wild-type mice in a macrophage and CD8 T cell-dependent manner. MerTK-/- mice showed increased counts of tumor antigen-specific CD8 T cells in the peripheral blood after tumor-directed RT alone and in combination with agonist anti-OX40. Warfarin therapy phenocopied MerTK-/- for single-flank tumors treated with RT and improved abscopal responses for RT combined with anti-CTLA4. Patients on warfarin therapy when treated with SABR for non-small cell lung cancer had higher progression-free survival rates compared with non-warfarin users. CONCLUSIONS: MerTK inhibits adaptive immune responses after SABR. Because warfarin inhibits MerTK signaling and phenocopies genetic deletion of MerTK in mice, warfarin therapy may have beneficial effects in combination with SABR and immune therapy in patients with cancer.
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Imunidade Adaptativa/genética , Imunidade Adaptativa/efeitos da radiação , Técnicas de Inativação de Genes , c-Mer Tirosina Quinase/deficiência , c-Mer Tirosina Quinase/genética , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Terapia de Alvo Molecular , Varfarina/farmacologia , Varfarina/uso terapêuticoRESUMO
Invertebrates perform many vital functions in agricultural production, but many taxa are in decline, including pest natural enemies. Action is needed to increase their abundance if more sustainable agricultural systems are to be achieved. Conservation biological control (CBC) is a key component of integrated pest management yet has failed to be widely adopted in mainstream agriculture. Approaches to improving conservation biological control have been largely ad hoc. Two approaches are described to improve this process, one based upon pest natural enemy ecology and resource provision while the other focusses on the ecosystem service delivery using the QuESSA (Quantification of Ecological Services for Sustainable Agriculture) project as an example. In this project, a predictive scoring system was developed to show the potential of five seminatural habitat categories to provide biological control, from which predictive maps were generated for Europe. Actual biological control was measured in a series of case studies using sentinel systems (insect or seed prey), trade-offs between ecosystem services were explored, and heatmaps of biological control were generated. The overall conclusion from the QuESSA project was that results were context specific, indicating that more targeted approaches to CBC are needed. This may include designing new habitats or modifying existing habitats to support the types of natural enemies required for specific crops or pests.