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1.
PLoS Pathog ; 17(11): e1010033, 2021 11.
Article in English | MEDLINE | ID: mdl-34780568

ABSTRACT

Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.


Subject(s)
Animal Diseases/pathology , Cell Differentiation , Communicable Diseases/pathology , Facial Neoplasms/veterinary , Gene Expression Regulation, Neoplastic , Proteome/metabolism , Schwann Cells/pathology , Animal Diseases/genetics , Animal Diseases/metabolism , Animals , Biological Variation, Population , Communicable Diseases/genetics , Communicable Diseases/metabolism , Facial Neoplasms/classification , Gene Expression Profiling , Marsupialia , Proteome/analysis , Schwann Cells/metabolism , Transcriptome
2.
Phys Rev Lett ; 128(20): 203603, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35657853

ABSTRACT

We report tunable excitation-induced dipole-dipole interactions between silicon-vacancy color centers in diamond at cryogenic temperatures. These interactions couple centers into collective states, and excitation-induced shifts tag the excitation level of these collective states against the background of excited single centers. By characterizing the phase and amplitude of the spectrally resolved interaction-induced signal, we observe oscillations in the interaction strength and population state of the collective states as a function of excitation pulse area. Our results demonstrate that excitation-induced dipole-dipole interactions between color centers provide a route to manipulating collective intercenter states in the context of a congested, inhomogeneous ensemble.

3.
Immunology ; 163(2): 169-184, 2021 06.
Article in English | MEDLINE | ID: mdl-33460454

ABSTRACT

Transmissible cancers are malignant cells that can spread between individuals of a population, akin to both a parasite and a mobile graft. The survival of the Tasmanian devil, the largest remaining marsupial carnivore, is threatened by the remarkable emergence of two independent lineages of transmissible cancer, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to major histocompatibility complex class I (MHC-I) molecules from Tasmanian devil cells and representative cell lines of each transmissible cancer. Here, we show that DFT1 + IFN-γ and DFT2 cell lines express a restricted repertoire of MHC-I allotypes compared with fibroblast cells, potentially reducing the breadth of peptide presentation. Comparison of the peptidomes from DFT1 + IFNγ, DFT2 and host fibroblast cells demonstrates a dominant motif, despite differences in MHC-I allotypes between the cell lines, with preference for a hydrophobic leucine residue at position 3 and position Ω of peptides. DFT1 and DFT2 both present peptides derived from neural proteins, which reflects a shared cellular origin that could be exploited for vaccine design. These results suggest that polymorphisms in MHC-I molecules between tumours and host can be 'hidden' by a common peptide motif, providing the potential for permissive passage of infectious cells and demonstrating complexity in mammalian histocompatibility barriers.


Subject(s)
Antigens, Neoplasm/metabolism , Cancer Vaccines/immunology , Facial Neoplasms/immunology , Immunotherapy/methods , Marsupialia/immunology , Neoplastic Cells, Circulating/pathology , Peptides/metabolism , Amino Acid Motifs/genetics , Animals , Antigen Presentation , Antigens, Neoplasm/genetics , Cell Line, Tumor , Histocompatibility , Histocompatibility Antigens Class I/metabolism , Peptides/genetics , Polymorphism, Genetic , Protein Binding
4.
Immunol Invest ; 48(7): 719-736, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31161832

ABSTRACT

The Tasmanian devil is the only mammalian species to harbour two independent lineages of contagious cancer. Devil facial tumour 1 (DFT1) emerged in the 1990s and has caused significant population declines. Devil facial tumour 2 (DFT2) was identified in 2014, and evidence indicates that this new tumour has emerged independently of DFT1. While DFT1 is widespread across Tasmania, DFT2 is currently found only on the Channel Peninsula in south east Tasmania. Allograft transmission of cancer cells should be prevented by major histocompatibility complex (MHC) molecules. DFT1 avoids immune detection by downregulating MHC class I expression, which can be reversed by treatment with interferon-gamma (IFNγ), while DFT2 currently circulates in hosts with a similar MHC class I genotype to the tumour. Wild Tasmanian devil numbers have not recovered from the emergence of DFT1, and it is feared that widespread transmission of DFT2 will be devastating to the remaining wild population. A preventative solution for the management of the disease is needed. Here, we review the current research on immune responses to devil facial tumours and vaccine strategies against DFT1 and outline our plans moving forward to develop a specific, effective vaccine to support the wild Tasmanian devil population against the threat of these two transmissible tumours.


Subject(s)
Antigens, Neoplasm/immunology , Cancer Vaccines/immunology , Facial Neoplasms/immunology , Facial Neoplasms/veterinary , Animals , Cancer Vaccines/therapeutic use , Facial Neoplasms/genetics , Facial Neoplasms/therapy , Gene Expression Regulation, Neoplastic , Histocompatibility Antigens Class I/genetics , Immunotherapy , Marsupialia , Vaccination , Vaccines, Subunit
5.
Adv Sci (Weinh) ; : e2402048, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961641

ABSTRACT

Ferro-rotational (FR) materials, renowned for their distinctive material functionalities, present challenges in the growth of homo-FR crystals (i.e., single FR domain). This study explores a cost-effective approach to growing homo-FR helimagnetic RbFe(SO4)2 (RFSO) crystals by lowering the crystal growth temperature below the TFR threshold using the high-pressure hydrothermal method. Through polarized neutron diffraction experiments, it is observed that nearly 86% of RFSO crystals consist of a homo-FR domain. Notably, RFSO displays remarkable stability in the FR phase, with an exceptionally high TFR of ≈573 K. Furthermore, RFSO exhibits a chiral helical magnetic structure with switchable ferroelectric polarization below 4 K. Importantly, external electric fields can induce a single magnetic domain state and manipulate its magnetic chirality. The findings suggest that the search for new FR magnets with outstanding material properties should consider magnetic sulfates as promising candidates.

6.
Evol Appl ; 17(3): e13670, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38468711

ABSTRACT

Since the emergence of a transmissible cancer, devil facial tumour disease (DFT1), in the 1980s, wild Tasmanian devil populations have been in decline. In 2016, a second, independently evolved transmissible cancer (DFT2) was discovered raising concerns for survival of the host species. Here, we applied experimental and modelling frameworks to examine competition dynamics between the two transmissible cancers in vitro. Using representative cell lines for DFT1 and DFT2, we have found that in monoculture, DFT2 grows twice as fast as DFT1 but reaches lower maximum cell densities. Using co-cultures, we demonstrate that DFT2 outcompetes DFT1: the number of DFT1 cells decreasing over time, never reaching exponential growth. This phenomenon could not be replicated when cells were grown separated by a semi-permeable membrane, consistent with exertion of mechanical stress on DFT1 cells by DFT2. A logistic model and a Lotka-Volterra competition model were used to interrogate monoculture and co-culture growth curves, respectively, suggesting DFT2 is a better competitor than DFT1, but also showing that competition outcomes might depend on the initial number of cells, at least in the laboratory. We provide theories how the in vitro results could be translated to observations in the wild and propose that these results may indicate that although DFT2 is currently in a smaller geographic area than DFT1, it could have the potential to outcompete DFT1. Furthermore, we provide a framework for improving the parameterization of epidemiological models applied to these cancer lineages, which will inform future disease management.

7.
Surg Endosc ; 27(10): 3555-63, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23584820

ABSTRACT

BACKGROUND: Prolonged operative duration is associated with increased postoperative morbidity and mortality. Although laparoscopic colectomy (LC) is associated with longer operative duration compared with open colectomy (OC), research shows paradoxically decreased morbidity following LC versus OC. The direct impact of operative duration on postoperative pulmonary complications (PPC) following LC versus OC has not been analyzed. METHODS: We queried the ACS/NSQIP 2009-2010 Public Use File for patients who underwent elective LC and OC. The associations between operative duration and a PPC (pneumonia, intubation >48 h, and unplanned intubation) were evaluated. Multivariable regression models were created to determine the independent effect of operative time on the development of PPC controlling for LC versus OC. RESULTS: A total of 25,419 colectomies (13,741 laparoscopic and 11,678 open) were reviewed; 765 (3 %) patients experienced at least one PPC. Regression modeling demonstrated that for both LC and OC each 60-min increase in operative time up to 480 min was associated with 13 % increased odds of PPC [odds ratio (OR) 1.13; 95 % confidence interval (CI) 1.07-1.19]. Beyond 480 min, each additional 60-min interval was associated with 33 % increased risk of PPC (OR 1.33; 95 % CI 1.12-1.58). Overall, PPCs occurred half as often following LC [270 (2 %) laparoscopic vs. 497 (4.3 %) open; OR 0.45; 95 % CI 0.39-0.53]. CONCLUSIONS: Operative duration is independently associated with increased risk of PPC in patients undergoing LC and OC. However, a laparoscopic approach carries half the absolute risk of PPC and, when safe, should be preferentially utilized despite a potential for prolonged operative duration.


Subject(s)
Colectomy/methods , Elective Surgical Procedures/methods , Laparoscopy/methods , Laparotomy/methods , Operative Time , Pneumonia/etiology , Postoperative Complications/etiology , Time Factors , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid , Elective Surgical Procedures/statistics & numerical data , Female , Hospital Mortality , Humans , Intubation, Gastrointestinal , Laparotomy/statistics & numerical data , Length of Stay , Male , Middle Aged , Narcotics/adverse effects , Pain Management , Pain, Postoperative/drug therapy , Pneumonia/epidemiology , Pneumonia/prevention & control , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Respiration, Artificial/statistics & numerical data , Risk Factors , Spirometry
8.
Cochrane Database Syst Rev ; (11): CD003985, 2011 Nov 09.
Article in English | MEDLINE | ID: mdl-22071810

ABSTRACT

BACKGROUND: Helmets reduce bicycle-related head injuries, particularly in single vehicle crashes and those where the head strikes the ground. We aimed to identify non-legislative interventions for promoting helmet use among children, so future interventions can be designed on a firm evidence base. OBJECTIVES: To assess the effectiveness of non-legislative interventions in increasing helmet use among children; to identify possible reasons for differences in effectiveness of interventions; to evaluate effectiveness with respect to social group; to identify adverse consequences of interventions. SEARCH METHODS: We searched the following databases: Cochrane Injuries Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; PsycINFO (Ovid); PsycEXTRA (Ovid); CINAHL (EBSCO); ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED); Social Sciences Citation Index (SSCI); Conference Proceedings Citation Index-Science (CPCI-S); and PubMed from inception to April 2009; TRANSPORT to 2007; and manually searched other sources of data. SELECTION CRITERIA: We included RCTs and CBAs. Studies included participants aged 0 to 18 years, described interventions promoting helmet use not requiring enactment of legislation and reported observed helmet wearing, self reported helmet ownership or self reported helmet wearing. DATA COLLECTION AND ANALYSIS: Two independent review authors selected studies for inclusion and extracted data. We used random-effects models to estimate pooled odds ratios (ORs) (with 95% confidence interval (CI)). We explored heterogeneity with subgroup analyses. MAIN RESULTS: We included 29 studies in the review, 21 of which were included in at least one meta-analysis. Non-legislative interventions increased observed helmet wearing (11 studies: OR 2.08, 95% CI 1.29 to 3.34). The effect was most marked amongst community-based interventions (four studies: OR 4.30, 95% 2.24 to 8.25) and those providing free helmets (two studies: OR 4.35, 95% CI 2.13 to 8.89). Significant effects were also found amongst school-based interventions (eight studies: OR 1.73, CI 95% 1.03 to 2.91), with a smaller effect found for interventions providing education only (three studies: OR 1.43, 95% CI 1.09 to 1.88). No significant effect was found for providing subsidised helmets (seven studies: OR 2.02, 95% CI 0.98 to 4.17). Interventions provided to younger children (aged under 12) may be more effective (five studies: OR 2.50, 95% CI 1.17 to 5.37) than those provided to children of all ages (five studies: OR 1.83, 95% CI 0.98 to 3.42).Interventions were only effective in increasing self reported helmet ownership where they provided free helmets (three studies: OR 11.63, 95% CI 2.14 to 63.16).Interventions were effective in increasing self reported helmet wearing (nine studies: OR 3.27, 95% CI 1.56 to 6.87), including those undertaken in schools (six studies: OR 4.21, 95% CI 1.06 to 16.74), providing free helmets (three studies: OR 7.27, 95% CI 1.28 to 41.44), providing education only (seven studies: OR 1.93, 95% CI 1.03 to 3.63) and in healthcare settings (two studies: OR 2.78, 95% CI 1.38 to 5.61). AUTHORS' CONCLUSIONS: Non-legislative interventions appear to be effective in increasing observed helmet use, particularly community-based interventions and those providing free helmets. Those set in schools appear to be effective but possibly less so than community-based interventions. Interventions providing education only are less effective than those providing free helmets. There is insufficient evidence to recommend providing subsidised helmets at present. Interventions may be more effective if provided to younger rather than older children. There is evidence that interventions offered in healthcare settings can increase self reported helmet wearing.Further high-quality studies are needed to explore whether non-legislative interventions increase helmet wearing, and particularly the effect of providing subsided as opposed to free helmets, and of providing interventions in healthcare settings as opposed to in schools or communities. Alternative interventions (e.g. those including peer educators, those aimed at developing safety skills including skills in decision making and resisting peer pressure or those aimed at improving self esteem or self efficacy) need developing and testing, particularly for 11 to 18 year olds. The effect of interventions in countries with existing cycle helmet legislation and in low and middle-income countries also requires investigation.


Subject(s)
Bicycling , Head Protective Devices/statistics & numerical data , Adolescent , Bicycling/legislation & jurisprudence , Bicycling/statistics & numerical data , Child , Child, Preschool , Craniocerebral Trauma/prevention & control , Head Protective Devices/supply & distribution , Humans , Program Development
9.
Mol Ther Methods Clin Dev ; 22: 183-195, 2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34485604

ABSTRACT

Adeno-associated virus (AAV)-based gene therapies have recently shown promise as a novel treatment for hereditary diseases. Due to the viral origin of the vector capsid, however, cellular immune response may be elicited that could eliminate transduced target cells. To monitor cellular immune responses in clinical trials, we optimized and bioanalytically validated a sensitive, robust, and reliable interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assay. For method performance validation, human peripheral blood mononuclear cells (PBMCs) were stimulated with peptides derived from AAV5 capsid proteins and the encoded transgene product, human blood clotting factor VIII (FVIII), in addition to positive controls, such as peptides from the 65-kDa phosphoprotein of cytomegalovirus. We statistically assessed the limit of detection and confirmatory cutpoint, evaluated precision and linearity, and confirmed specificity using HIV peptides. Robustness parameter ranges and sample stability periods were established. The validated IFN-γ ELISpot assay was then implemented in an AAV5-FVIII gene therapy clinical trial. Cellular immune responses against the AAV5 capsid were observed in most participants as soon as 2 weeks following dose administration; only limited responses against the transgene product were detected. These data underscore the value of using validated methods for monitoring cellular immunity in AAV gene therapy trials.

10.
Evol Appl ; 13(7): 1719-1732, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32821279

ABSTRACT

Ecological and evolutionary concepts have been widely adopted to understand host-pathogen dynamics, and more recently, integrated into wildlife disease management. Cancer is a ubiquitous disease that affects most metazoan species; however, the role of oncogenic phenomena in eco-evolutionary processes and its implications for wildlife management and conservation remains undeveloped. Despite the pervasive nature of cancer across taxa, our ability to detect its occurrence, progression and prevalence in wildlife populations is constrained due to logistic and diagnostic limitations, which suggests that most cancers in the wild are unreported and understudied. Nevertheless, an increasing number of virus-associated and directly transmissible cancers in terrestrial and aquatic environments have been detected. Furthermore, anthropogenic activities and sudden environmental changes are increasingly associated with cancer incidence in wildlife. This highlights the need to upscale surveillance efforts, collection of critical data and developing novel approaches for studying the emergence and evolution of cancers in the wild. Here, we discuss the relevance of malignant cells as important agents of selection and offer a holistic framework to understand the interplay of ecological, epidemiological and evolutionary dynamics of cancer in wildlife. We use a directly transmissible cancer (devil facial tumour disease) as a model system to reveal the potential evolutionary dynamics and broader ecological effects of cancer epidemics in wildlife. We provide further examples of tumour-host interactions and trade-offs that may lead to changes in life histories, and epidemiological and population dynamics. Within this framework, we explore immunological strategies at the individual level as well as transgenerational adaptations at the population level. Then, we highlight the need to integrate multiple disciplines to undertake comparative cancer research at the human-domestic-wildlife interface and their environments. Finally, we suggest strategies for screening cancer incidence in wildlife and discuss how to integrate ecological and evolutionary concepts in the management of current and future cancer epizootics.

11.
Cytometry A ; 75(12): 1040-50, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19845018

ABSTRACT

Foxp3 is a key marker for CD4(+) regulatory T cells (T(regs)) and was used in developing a multiparameter flow cytometric panel to identify T(regs). Achieving reproducible staining and analysis first required optimization of Foxp3 staining. We present a comparative study of PCH101, 236A/E7, 3G3, 206D, 150D, and 259D/C7 clones of anti-human-Foxp3 antibodies used in combination with five different fixation/permeabilization buffers. Staining for CD25, CD152, and CD127 was also compared between fixation/permeabilization treatments. Promising antibody/buffer combinations were tested in a panel of peripheral blood mononuclear cells from 10 individuals, and then on fresh versus frozen cells from four individuals. Finally, different fluorochromes coupled to two representative antibodies were compared to optimize separation of Foxp3(+) from Foxp3(-) events. Foxp3 gates were set using two gating strategies based on CD127(+)CD25(-) "non-T(regs)" or based on isotype controls. For Foxp3 staining, the best conditions for fixation/permeabilization were obtained using the eBioscience Foxp3, Imgenex, BioLegend, and BD Foxp3 buffers. Comparing results from 10 subjects, 259D/C7, PCH101, 236A/E7, and 206D antibodies yielded statistically higher levels of Foxp3 cells than those by 150D and 3G3 antibodies (mean = 6.9, 5.1, 4.7, and 3.7% compared with 1.7, and 0.3% of CD25(+)Foxp3(+) events within CD4(+) cells, respectively). Importantly, the "nonspecificity" of some antibodies observed with a Foxp3 gate based on isotype controls could be eliminated by setting the Foxp3 gate on "non-T(regs)". Better separation of Foxp3(+) and Foxp3(-) populations was observed using the PCH101 clone coupled to Alexa647 compared with FITC or the 259D/C7 clone coupled to PE compared with Alexa488 fluorochrome. Foxp3 staining can be highly variable and depends on the choice of antibody/buffer pair and the fluorochrome used. Selecting the correct population for setting the Foxp3 gate is critical to avoid including non-T(regs) in the Foxp3(+) gate. The experiments presented here will aid in optimization of flow cytometry staining panels to quantify T(reg) frequencies in humans.


Subject(s)
Antibodies/immunology , CD4 Antigens/metabolism , Forkhead Transcription Factors/immunology , Interleukin-2 Receptor alpha Subunit/metabolism , T-Lymphocytes, Regulatory/cytology , Tissue Fixation , Buffers , Humans , Permeability , Staining and Labeling
12.
Elife ; 72018 08 14.
Article in English | MEDLINE | ID: mdl-30103855

ABSTRACT

Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer circulating in the Tasmanian devil (Sarcophilus harrisii), a species which already harbours a more widespread contagious cancer, Devil Facial Tumour 1 (DFT1). Here we show that in contrast to DFT1, DFT2 cells express major histocompatibility complex (MHC) class I molecules, demonstrating that loss of MHC is not necessary for the emergence of a contagious cancer. However, the most highly expressed MHC class I alleles in DFT2 cells are common among host devils or non-polymorphic, reducing immunogenicity in a population sharing these alleles. In parallel, MHC class I loss is emerging in vivo, thus DFT2 may be mimicking the evolutionary trajectory of DFT1. Based on these results we propose that contagious cancers may exploit partial histocompatibility between the tumour and host, but that loss of allogeneic antigens could facilitate widespread transmission of DFT2.


Subject(s)
Biological Evolution , Facial Neoplasms/genetics , Histocompatibility Antigens Class I/genetics , Alleles , Animals , Facial Neoplasms/physiopathology , Marsupialia/genetics , Marsupialia/physiology
13.
J Immunol Methods ; 326(1-2): 93-115, 2007 Sep 30.
Article in English | MEDLINE | ID: mdl-17707394

ABSTRACT

Although cryopreservation of peripheral blood mononuclear cells (PBMC) is a commonly used technique, the degree to which it affects subsequent functional studies has not been well defined. Here we demonstrate that long-term cryopreservation has detrimental effects on T cell IFN-gamma responses in human immunodeficiency virus (HIV) infected individuals. Long-term cryopreservation caused marked decreases in CD4(+) T cell responses to whole proteins (HIV p55 and cytomegalovirus (CMV) lysate) and HIV peptides, and more limited decreases in CD8(+) T cell responses to whole proteins. These losses were more apparent in cells stored for greater than one year compared to less than six months. CD8(+) T cell responses to peptides and peptide pools were well preserved. Loss of both CD4(+) and CD8(+) T cell responses to CMV peptide pools were minimal in HIV-negative individuals. Addition of exogenous antigen presenting cells (APC) did not restore CD4(+) T cell responses to peptide stimulation and partially restored T cell IFN-gamma responses to p55 protein. Overnight resting of thawed cells did not restore T cell IFN-gamma responses to peptide or whole protein stimulation. A selective loss of phenotypically defined effector cells did not explain the decrement of responses, although cryopreservation did increase CD4(+) T cell apoptosis, possibly contributing to the loss of responses. These data suggest that the impact of cryopreservation should be carefully considered in future vaccine and pathogenesis studies. In HIV-infected individuals short-term cryopreservation may be acceptable for measuring CD4(+) and CD8(+) T cell responses. Long-term cryopreservation, however, may lead to the loss of CD4(+) T cell responses and mild skewing of T cell phenotypic marker expression.


Subject(s)
Cryopreservation , T-Lymphocytes , Acute Disease , Apoptosis/immunology , B-Lymphocytes/immunology , Cell Line , Cell Line, Transformed , Cells, Cultured , Chronic Disease , Coculture Techniques , Cytomegalovirus/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/pathology , HIV/immunology , HIV Infections/immunology , HIV Infections/pathology , Humans , Male , T-Lymphocytes/cytology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Time Factors
14.
Nurse Educ Pract ; 15(6): 561-6, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26482402

ABSTRACT

Clinical practicum experiences for nursing students provides the students an opportunity to apply concepts learned in class, practice skills learned in lab, and interact with patients, families, and other nurses. Although students look forward to these experiences, they often feel intimated and anxious about them. Clinical instructors play an important role in this experience and can either help or hinder student learning and self-efficacy. Using Bandura's Social Learning Theory as foundation, this descriptive study examined the relationship between perceived instructor effectiveness and student self-efficacy. Data were collected from a BSN school of nursing at a Midwestern USA comprehensive masters university. The instruments used were the Nursing Clinical Teacher Effectiveness Inventory (NCTEI) and the student self-efficacy (SSE) questionnaire. Participants (n = 236) were from a traditional nursing program with 86% female and 14% male. Data was analyzed using Pearson's correlation and MANCOVA. Results indicated: Out of the five areas of attributes, one area showed significant (p < .01) difference between the lower and higher self-efficacy groups and with specific teacher behaviors within the Evaluation category. Students with high self-efficacy reported faculty who suggested ways to improve, identified strengths and weaknesses, observed frequently, communicated expectations, gives positive reinforcement ad corrects without belittling. This can help faculty develop behaviors that increases student learning and student self-efficacy.


Subject(s)
Education, Nursing, Baccalaureate , Faculty, Nursing , Self Efficacy , Students, Nursing/psychology , Adult , Female , Humans , Learning , Male , Midwestern United States , Nursing Education Research , Preceptorship/methods , Social Theory , Surveys and Questionnaires
15.
Int J Sports Physiol Perform ; 10(4): 464-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25365032

ABSTRACT

PURPOSE: To investigate the effect of ingesting a caffeinated carbohydrate gel (CC) 10 minutes prior on 2000-m rowing performance compared with a carbohydrate-only placebo gel (CP). METHODS: A counterbalanced, single-blind, crossover study design was employed (N=13). All participants completed 1 familiarization trial followed by 2 experimental rowing time trials. The experimental trials were performed 10 min after ingesting CP (21.6 g of carbohydrate, 0 mg caffeine) or CC (21.6 g carbohydrate, 100 mg caffeine), and heart rate (HR), oxygen consumption (VO2), carbon dioxide production, minute ventilation (VE), respiratory-exchange ratio (RER), rating of perceived exertion (RPE), gastrointestinal discomfort (GI), and thirst perception (Thirst) were recorded every 200 m. Blood lactate [La-] was recorded immediately before and after exercise. RESULTS: A pairedsamples t test identified a significant improvement in 2000-m performance of 5.2±3.9 s (1.1%±1.7%; P=.034). Two-way repeated-measures ANOVA revealed no significant treatment effect for HR (177±8 vs 177±9 beats/min, P=.817), VO2 (46.1±6.5 vs 46.6±6.2 mL·kg(-1)·min(-1), P=.590), VE (121.8±14.7 vs 124.8±15.7 L/min, P=.490), RPE, GI, or Thirst for CP and CC, respectively. Paired-samples t tests revealed no treatment effect for postexercise [La-] between CP and CC (11.72±2.69 vs 12.26±3.13 mmol/L, P=.534). CONCLUSION: A relatively low dose of caffeine (1.3±0.1 mg/kg body mass) in an isotonic carbohydrate gel ingested only 10 min before performance improved 2000-m rowing time by 5.2±7.8 s (1.1%±1.7%).


Subject(s)
Athletic Performance/physiology , Caffeine/administration & dosage , Dietary Carbohydrates/administration & dosage , Physical Exertion/drug effects , Running/physiology , Administration, Oral , Central Nervous System Stimulants/administration & dosage , Cross-Over Studies , Dose-Response Relationship, Drug , Drug Combinations , Exercise Test , Gels , Humans , Male , Oxygen Consumption/physiology , Single-Blind Method , Young Adult
16.
Environ Sci Pollut Res Int ; 22(7): 5152-63, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25369917

ABSTRACT

Knowledge of how biochar impacts soil denitrification kinetics as well as the mechanisms of interactions is essential in order to better predict the nitrous oxide (N2O) mitigation capacity of biochar additions. This study had multiple experiments in which the effect of three biochar materials produced from corn stover (Zea mays L.), ponderosa pine wood residue (Pinus ponderosa Douglas ex Lawson and C. Lawson), switchgrass (Panicum virgatum L.), and their corresponding biomass materials (corn stover, ponderosa pine wood residue, and switchgrass) on cumulative N2O emissions and total denitrification in soils from two different landscape positions (crest and footslope) were studied under varying water-filled pore space (40, 70, and 90% WFPS). Cumulative N2O emissions were reduced by 30 to 70% in both crest and footslope soils. The effect of biochars and biomass treatments on cumulative N2O emissions and total denitrification were only observed at ≥40% WFPS. The denitrification enzyme activity (DEA) kinetic parameters, K s (half-saturation constant), and V max (maximum DEA rate) were both significantly reduced by biochar treatments, with reductions of 70-80% in footslope soil and 80-90 % in the crest soil. The activation energy (E a) and enthalpy of activation of DEA (ΔH) were both increased with biochar application. The trends in DEA rate constants (K s and V max) were correlated by the trends of thermodynamic parameters (activation energy E a and enthalpy of activation ΔH) for denitrifying enzyme activity (DEA). The rate constant V max/K s evaluated the capacity of biochars to mitigate the denitrification process. Denitrifying enzyme kinetic parameters can be useful in evaluating the ability of biochars to mitigate N2O gas losses from soil.


Subject(s)
Biomass , Charcoal , Denitrification , Soil/chemistry , Kinetics , Nitrous Oxide/chemistry , Panicum , Pinus ponderosa , Water/chemistry , Wood , Zea mays
17.
Eur J Cardiothorac Surg ; 43(2): 312-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22611143

ABSTRACT

OBJECTIVES: To analyse the indications, operative techniques, postoperative morbidity, mortality and long-term outcomes of patients who underwent pneumonectomy for benign lung disease. METHODS: We retrospectively reviewed our institutional database for patients who underwent a pneumonectomy for benign lung disease from January 1991 to June 2010. The data were queried for the indications for surgery, details of operative technique, development of perioperative complications, mortality and long-term survival. RESULTS: There were 32 patients, 19 men (59%) and 13 women, with a mean age of 48 years (17-78). Indications for pneumonectomy included pulmonary tuberculosis in 10 patients (31%), chronic septic lung disease in seven (22%), invasive opportunistic infections in five (16%), fibrosing mediastinitis in four (12%) and other in six (19%). Pneumonectomies were left-sided in 17 (53%) and right-sided in 15 patients; nine (28%) were completion pneumonectomies. Intraoperatively, intrapericardial isolation was performed in 21 (66%) patients and extrapleural dissection in seven (22%); bronchial reinforcement was performed in 25 (78%). Operative mortality occurred in two (6%) patients. Major complications occurred in 12 (38%) patients; no patient developed bronchopleural fistula or postpneumonectomy empyema requiring intervention. Overall 5-year survival was 75% (95% CI 56.2-87.9), with a mean follow-up of 99 months. CONCLUSIONS: Pneumonectomy for benign disease is a high-risk procedure performed for a variety of indications. A detailed operative technique is of the utmost importance to minimize postoperative morbidity and mortality. Despite an increased perioperative risk, the long-term outcomes can be especially satisfactory. Pneumonectomy for benign disease should continue to be a treatment option for carefully selected patients.


Subject(s)
Lung Diseases/surgery , Pneumonectomy/methods , Adolescent , Adult , Aged , Female , Humans , Lung Diseases/mortality , Male , Middle Aged , Pneumonectomy/mortality , Postoperative Complications/etiology , Postoperative Complications/mortality , Retrospective Studies , Treatment Outcome , Young Adult
18.
Ann Thorac Surg ; 95(6): 1859-65; discussion 1865-6, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23415238

ABSTRACT

BACKGROUND: Residual disease at the bronchial margin after resection of non-small cell lung cancer (NSCLC) adversely affects survival. To ensure an R0 resection, thoracic surgeons commonly use intraoperative frozen section analysis of the bronchial margin. We hypothesize that frozen section of the bronchial margin is rarely positive and seldom changes intraoperative management. METHODS: Our institutional Society of Thoracic Surgery database was queried for all patients undergoing planned lobectomy for NSCLC from 2009 to 2011. Clinical variables, intraoperative data, and postoperative outcomes were reviewed. Specifically, intraoperative frozen section and final pathology results of all bronchial margins were examined. The frequency that frozen section results affected intraoperative decision making was evaluated. RESULTS: A total of 287 lobectomies for NSCLC were performed. Frozen section of the bronchial margin was performed in 270 patients (94.1%). There were 6 (2.2%) true-positive bronchial margins and 1 (0.4%) false-negative margin. In no cases did a positive frozen section lead to a change in operative management; reasons included unable to tolerate further resection (n = 5) and advanced-stage disease (n = 1). Positive margins were more frequent with open techniques (7%) than in video-assisted thoracoscopic operations (0.05%; p < 0.01). Tumors with positive margins were closer to the bronchial margin (1.0 vs 2.5 cm; p = 0.04). Frozen section was not used in 17 patients (5.9%), and none had positive margins on final pathology. CONCLUSIONS: Frozen section analysis of the bronchial margin rarely yields a positive result and infrequently changes intraoperative management in patients undergoing NSCLC resection. These data support selective use of intraoperative frozen section of bronchial margins during lobectomy for NSCLC.


Subject(s)
Bronchi/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Frozen Sections , Lung Neoplasms/surgery , Age Factors , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Databases, Factual , Disease-Free Survival , Education, Medical, Continuing , Female , Humans , Intraoperative Care/methods , Length of Stay , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm, Residual , Operative Time , Pneumonectomy/methods , Pneumonectomy/mortality , Prognosis , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Sex Factors , Survival Analysis , Treatment Outcome
19.
JAMA Surg ; 148(2): 118-26, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23560282

ABSTRACT

OBJECTIVE: To analyze postoperative outcomes, morbidity, and mortality following enterocutaneous fistula (ECF) takedown. DESIGN, SETTING, AND PATIENTS: Retrospective review of the complete medical records of patients who presented to a single tertiary care referral center from December 24, 1987, to June 18, 2010, and subsequently underwent definitive surgical treatment for ECF originating from the stomach, small bowel, colon, or rectum. MAIN OUTCOME MEASURES: Postoperative fistula recurrence and mortality. RESULTS: A total of 153 patients received operative intervention for ECF. Most ECFs were referred to us from outside institutions (75.2%), high output (52.3%), originating from the small bowel (88.2%), and iatrogenic in cause (66.7%). Successful ECF closure was ultimately achieved in 128 patients (83.7%). Six patients (3.9%) died within 30 days of surgery, and overall 1-year mortality was 15.0%. Postoperative complications occurred in 134 patients, for an overall morbidity rate of 87.6%. Significant risk factors for fistula recurrence were numerous, but postoperative ventilation for longer than 48 hours, organ space surgical site infection, and blood transfusion within 72 hours of surgery carried the most considerable impact (relative risks, 4.87, 4.07, and 3.91, respectively; P < .05). Risk of 1-year mortality was also associated with multiple risk factors, the most substantial of which were postoperative pulmonary and infectious complications. Closure of abdominal fascia was protective against both recurrent ECF and mortality (relative risks, 0.47 and 0.38, respectively; P < .05). CONCLUSIONS: Understanding risk factors both associated with and protective against ECF recurrence and postoperative morbidity and mortality is imperative for appropriate ECF management. Closure of abdominal fascia is of utmost importance, and preventing postoperative complications must be prioritized to optimize patient outcomes.


Subject(s)
Digestive System Surgical Procedures/methods , Intestinal Fistula/surgery , Postoperative Complications/epidemiology , Risk Assessment/methods , Adult , Aged , Aged, 80 and over , Digestive System Surgical Procedures/adverse effects , Female , Humans , Intestinal Fistula/epidemiology , Male , Middle Aged , Morbidity/trends , Recurrence , Retrospective Studies , Risk Factors , Survival Rate/trends , United States/epidemiology , Young Adult
20.
Arch Surg ; 147(10): 946-53, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23070409

ABSTRACT

BACKGROUND: The Surgical Care Improvement Project (SCIP) Inf-9 guideline promotes removal of indwelling urinary catheters (IUCs) within 48 hours of surgery. OBJECTIVES: To determine whether a correlation exists between SCIP Inf-9 compliance and postoperative urinary tract infection (UTI) rates and whether an association exists between UTI rates and SCIP Inf-9 exemption status. DESIGN Retrospective case control study. SETTING: Southeastern academic medical center. PATIENTS: American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and SCIP Inf-9 compliance data were collected prospectively on randomly selected general and vascular surgery inpatients. Monthly UTI rates and SCIP Inf-9 compliance scores were tested for correlation. Complete NSQIP data for all the inpatients with postoperative UTIs were compared with a group of 100 random controls to determine whether an association exists between UTI rates and SCIP Inf-9 exemption status. MAIN OUTCOME MEASURE: Postoperative UTI. RESULTS: In 2459 patients reviewed, SCIP Inf-9 compliance increased over time, but this was not correlated with improved monthly UTI rates. Sixty-one of the 69 UTIs (88.4%) were compliant with SCIP Inf-9; however, 49 (71.0%) of these were considered exempt from the guideline and, therefore, the IUC was not removed within 48 hours of surgery. Retrospective review of 100 random controls showed a similar compliance rate (84.0%, P = .43) but a lower rate of exemption (23.5%, P < .001). The odds of developing a postoperative UTI were 8 times higher in patients deemed exempt from SCIP Inf-9 (odds ratio [OR], 7.99; 95% CI, 3.85-16.61). After controlling for differences between the 2 groups, the adjusted ORs slightly increased (OR, 8.34; 95% CI, 3.70-18.76). CONCLUSIONS: Most UTIs occurred in patients deemed exempt from SCIP Inf-9. Although compliance rates remain high, practices are not actually improving. Surgical Care Improvement Project Inf-9 guidelines should be modified with fewer exemptions to facilitate earlier removal of IUCs.


Subject(s)
Catheters, Indwelling/standards , Device Removal/standards , Postoperative Complications/prevention & control , Practice Guidelines as Topic , Quality Improvement/standards , Urinary Catheters/standards , Urinary Tract Infections/prevention & control , Bacteriuria/etiology , Bacteriuria/prevention & control , Case-Control Studies , Catheters, Indwelling/adverse effects , Causality , Cause of Death , Cross Infection/epidemiology , Cross Infection/etiology , Cross Infection/prevention & control , Evidence-Based Medicine , Female , Guideline Adherence/statistics & numerical data , Humans , Incidence , Length of Stay , Male , Middle Aged , Odds Ratio , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Survival Rate , United States , Urinary Catheters/adverse effects , Urinary Tract Infections/epidemiology , Urinary Tract Infections/etiology
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