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1.
Appetite ; 200: 107501, 2024 09 01.
Article in English | MEDLINE | ID: mdl-38763298

ABSTRACT

This study investigates the structure of factors that influence consumer intentions to both try and to consume cultured proteins, and their intentions to substitute vegan, vegetarian and omnivore diets with these alternative protein sources. Comprehensive survey data (N = 3862) was collected from three Nordic countries (Denmark, Finland, and Norway) and analysed using confirmatory factor analysis and structural equation modelling. Theoretically, this article draws from behavioural models of environmental psychology, identity theory, and attitude theory. Results indicate that beliefs about the necessity of an industry producing cultured proteins and impacts of cultured proteins on the global economy are significant predictors of consumer intentions. Moreover, participants who exhibited high levels of general and food innovativeness were more likely to express positive intentions to consume cultured proteins. Social norms influenced consumer intentions: Individuals surrounded by positive attitudes and intentions toward cultured proteins within their social networks were more inclined to want to consume these products. The predictor variables in the final model accounted for between 39% and 66% of the variance in the different cultured proteins related intentions. Understanding consumer intentions better can inform targeted communication strategies aimed at promoting the advantages of cultured proteins and facilitating its adoption.


Subject(s)
Consumer Behavior , Intention , Meat , Humans , Male , Female , Adult , Middle Aged , Young Adult , Food Preferences/psychology , Dairy Products , Animals , Surveys and Questionnaires , Finland , Adolescent , Diet, Vegetarian/psychology , Fishes , Aged , Social Norms , Dietary Proteins , Seafood , Norway , Health Knowledge, Attitudes, Practice , Diet/psychology , In Vitro Meat
2.
Public Health ; 232: 61-67, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744097

ABSTRACT

OBJECTIVES: We explored the early impact of changes to the UK alcohol tax system, implemented in August 2023, on the strength and price of alcoholic products available for sale on the website of the largest supermarket in England. STUDY DESIGN: Our comparative descriptive study using longitudinal brand-level data was not preregistered and should be considered exploratory. METHODS: Data were collected weekly (May to October 2023) using automated web scraping tools. Outcomes were product strength (% alcohol by volume [ABV]) and price (per 10 mL of pure alcohol and per litre of product). We undertook paired t-tests, two-sample Kolmogorov-Smirnov tests, and quantile regression to compare outcomes before and after the tax changes. Beer, cider, spirits, and ready-to-drinks (RTDs) were analysed separately. RESULTS: There was a reduction in the mean strength of beer, driven by manufacturers reformulating a small number of weaker beers, moving them into a lower tax band (<3.5%ABV). The mean price per 10 mL of alcohol and per litre of product was significantly higher after the new tax system for beer, cider, and spirits and significantly lower for RTDs. Increases in the price of beer tended to occur across the entire distribution, whereas increases in the price of cider occurred among more expensive products. CONCLUSIONS: Changes to product strength tended to occur among weaker products near the new lowest tax band, suggesting tax bands may be a potential stimulus for change. Reformulation of stronger products would have better public health potential. Longer term monitoring, including data on purchasing/consumption, is required.


Subject(s)
Alcoholic Beverages , Commerce , Taxes , Taxes/statistics & numerical data , Alcoholic Beverages/economics , Humans , Commerce/statistics & numerical data , United Kingdom , Beer/economics , Beer/statistics & numerical data , Alcohol Drinking/epidemiology , Supermarkets , Longitudinal Studies
3.
Public Health ; 226: 39-52, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38000113

ABSTRACT

OBJECTIVE: Alcohol consumption, smoking, and excess weight independently increase the risk of morbidity/mortality. Less is known about how they interact. This research aims to quantify the independent and joint associations of these exposures across health outcomes and identify whether these associations are synergistic. STUDY DESIGN: The protocol for this systematic review and meta-analysis was pre-registered (PROSPERO CRD42021231443). METHODS: Medline and Embase were searched between 1 January 2010 and 9 February 2022. Eligible peer-reviewed observational studies had to include adult participants from Organisation for Co-Operation and Development countries and report independent and joint associations between at least two eligible exposures (alcohol, smoking, and excess weight) and an ICD-10 outcome (or equivalent). For all estimates, we calculated the synergy index (SI) to identify whether joint associations were synergistic. Meta-analyses were conducted for outcomes with sufficiently homogenous data. RESULTS: The search returned 26,290 studies, of which 98 were included. Based on 138,130 participants, the combined effect (SI) of alcohol and smoking on head and neck cancer death/disease was 3.78 times greater than the additive effect of each exposure (95% confidence interval [CI] = 2.61, 5.48). Based on 2,603,939 participants, the combined effect of alcohol and excess weight on liver disease/death was 1.55 times greater than the additive effect of each exposure (95% CI = 1.33, 1.82). CONCLUSION: Synergistic associations suggest the true population-level risk may be underestimated. In the absence of bias, individuals with multiple risks would experience a greater absolute risk reduction from an intervention that targets a single exposure than individuals with a single risk.


Subject(s)
Alcohol Drinking , Smoking , Adult , Humans , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , Overweight
4.
BMC Infect Dis ; 20(1): 734, 2020 Oct 07.
Article in English | MEDLINE | ID: mdl-33028245

ABSTRACT

BACKGROUND: HIV continues to be the main determinant morbidity with high mortality rates in Sub-Saharan Africa, with a high number of patients being late presenters with advanced HIV. Clinical management of advanced HIV patients is thus complex and requires strict adherence to updated, empirical and simplified guidelines. The current study investigated the impact of the implementation of a new clinical guideline on the management of advanced HIV in Kinshasa, Democratic Republic of Congo (DRC). METHODS: A retrospective analysis of routine clinical data of advanced HIV patients was conducted for the periods; February 2016 to March 2017, before implementation of new guidelines, and November 2017 to July 2018, after the implementation of new guidelines. Eligible patients were patients with CD4 < 200 cell/µl and presenting with at least 1 of 4 opportunistic infections. Patient files were reviewed by a medical doctor and a committee of 3 other doctors for congruence. Statistical significance was set at 0.05%. RESULTS: Two hundred four and Two hundred thirty-one patients were eligible for inclusion before and after the implementation of new guidelines respectively. Sex and age distributions were similar for both periods, and median CD4 were 36 & 52 cell/µl, before and after the new guidelines implementation, respectively. 40.7% of patients had at least 1 missed/incorrect diagnosis before the new guidelines compared to 30% after new guidelines, p < 0.05. Clinical diagnosis for TB and toxoplasmosis were also much improved after the implementation of new guidelines. In addition, only 63% of patients had CD4 count test results before the new guidelines compared to 99% of patients after new guidelines. Death odds after the implementation of new guidelines were significantly lower than before new guidelines in a multivariate regression model that included patients CD4 count and 10 other covariates, p < 0.05. CONCLUSIONS: Simplification and implementation of a new and improved HIV clinical guideline coupled with the installation of laboratory equipment and point of care tests potentially helped reduce incorrect diagnosis and improve clinical outcomes of patients with advanced HIV. Regulating authorities should consider developing simplified versions of guidelines followed by the provision of basic diagnostic equipment to health centers.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , Adolescent , Adult , Ambulatory Care Facilities , CD4 Lymphocyte Count , Democratic Republic of the Congo , Female , Guidelines as Topic , HIV Infections/complications , HIV Infections/mortality , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , Toxoplasmosis/complications , Toxoplasmosis/diagnosis , Tuberculosis/complications , Tuberculosis/diagnosis , Young Adult
5.
Environ Sci Technol ; 53(16): 9656-9663, 2019 Aug 20.
Article in English | MEDLINE | ID: mdl-31347827

ABSTRACT

An eddy diffusion model using data from a desktop three-dimensioanl (3D) printer was developed under laboratory conditions and then coupled with Monte Carlo analysis to estimate the potential range of particulate concentrations in and around various industrial-size 3D printers, in this case large additive manufacturing processes using acrylonitrile-butadiene-styrene polymer feedstock. The model employed mass emission estimates determined from thermal gravimetric analysis and printer enclosure particle loss rates. Other model inputs included ranging terms for extrusion rate, temperature, print time, source-to-receiver distance, printer positions, particle size fraction, and environmental diffusivity estimates based on air changes per hour. Monte Carlo analysis bracketed measured environmental particulate concentrations associated with large-scale additive manufacturing processes (3D printing). Statistically, there was no difference between the average near-field particle concentrations measured and that of the model-derived average. However, the model began to vary more statistically, if not practically, from air-monitoring results in the far field. Diffusivity and extrusion rate emerged as the two most important variables in predicting environmental concentrations. This model can be used to estimate air concentrations over a range of varying conditions, such as one might employ in a "what if" type of evaluation to estimate employee exposure, for example, as a compliance effort with OSHA standard 29 CFR Part 1910.132, requiring a formal hazard assessment for work environments as a "before exposure" effort to determine if respiratory protection is needed.


Subject(s)
Acrylonitrile , Air Pollution, Indoor , Butadienes , Particle Size , Particulate Matter , Printing, Three-Dimensional
6.
Anal Biochem ; 534: 10-13, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28698001

ABSTRACT

Predicting antibody pair performance in a sandwich format streamlines development of antibody-based diagnostics and laboratory research tools, such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow immunoassays (LFAs). We have evaluated panels of monoclonal antibodies against the malarial parasite biomarker Plasmodium falciparum histidine rich protein 2 (HRP2), including 9 new monoclonal antibodies, using biolayer interferometry (BLI) and screened antibody pairs in a checkerboard ELISA. This study showed BLI predicts antibody pair ELISA performance for HRP2. Pairs that included capture antibodies with low off-rate constants and detection antibodies with high on-rate constants performed best in an ELISA format.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Protozoan/analysis , Enzyme-Linked Immunosorbent Assay , Plasmodium falciparum/chemistry , Protozoan Proteins/analysis , Antigen-Antibody Reactions , Antigens, Protozoan/immunology , Plasmodium falciparum/immunology , Protozoan Proteins/immunology
7.
J Occup Environ Hyg ; 12(7): D116-22, 2015.
Article in English | MEDLINE | ID: mdl-25625686

ABSTRACT

The calibration records of two direct reading instruments designated as condensation particle counters were examined to determine the number of times they were found to be out of tolerance at annual manufacturer's recalibration. Both instruments were found to be out of tolerance more times than within tolerance. And, it was concluded that annual calibration alone was insufficient to provide operational confidence in an instrument's response. Therefore, a method based on subsequent agreement with data gathered from a newly calibrated instrument was developed to confirm operational readiness between annual calibrations, hereafter referred to as bump testing. The method consists of measuring source particles produced by a gas grille spark igniter in a gallon-size jar. Sampling from this chamber with a newly calibrated instrument to determine the calibrated response over the particle concentration range of interest serves as a reference. Agreement between this reference response and subsequent responses at later dates implies that the instrument is performing as it was at the time of calibration. Side-by-side sampling allows the level of agreement between two or more instruments to be determined. This is useful when simultaneously collected data are compared for differences, i.e., background with process aerosol concentrations. A reference set of data was obtained using the spark igniter. The generation system was found to be reproducible and suitable to form the basis of calibration verification. The bump test is simple enough to be performed periodically throughout the calibration year or prior to field monitoring.


Subject(s)
Air Pollutants, Occupational/analysis , Environmental Monitoring/instrumentation , Particulate Matter/analysis , Aerosols/analysis , Calibration , Environmental Monitoring/methods , Environmental Monitoring/standards , Occupational Exposure/analysis
8.
J Orthop ; 36: 65-71, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36605459

ABSTRACT

Reverse Total Shoulder Arthroplasty is being increasingly performed, with indications in both elective and trauma settings. Accordingly, there are an increasing number of revision cases where glenoid bone loss is a concern. There are well recognised surgical techniques for dealing with mild to moderate glenoid wear, including eccentric reaming and impaction grafting. In cases of severe wear or uncontained glenoid defects these may not be suitable, and the surgeon may look to a customised implant to deal with such bone loss. There are several implant manufacturers who currently market and produce patient specific instrumentation and customised glenoid baseplates to achieve the best possible fixation in cases of severe bone loss. This article outlines some examples of custom implants currently available to surgeons, and the process by which they may be procured and used. Implant and surgical considerations, and key aspects of surgical technique are also covered. Literature on outcomes and complications following custom shoulder arthroplasty shows promising results, but at present is limited to relatively small case series with no long-term outcome data.

9.
Cell Rep ; 41(11): 111783, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36516760

ABSTRACT

Bacille Calmette-Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTMs) are opportunistic pathogens present ubiquitously in the environment. TB endemic countries experience higher exposure to NTMs, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy against TB. Therefore, we develop a mouse model (BCG + NTM) to simulate human BCG immunization regime and continuous NTM exposure. BCG + NTM mice exhibit superior and prolonged protection against pulmonary TB, with increased B cell influx and anti-Mtb antibodies in serum and airways, compared with BCG alone. Notably, spatial transcriptomics and immunohistochemistry reveal that BCG + NTM mice formed B cell aggregates with features of germinal center development, which correlate with reduced Mtb burden. Our studies suggest a direct relationship between NTM exposure and TB protection, with B cells playing a crucial role.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Mice , Humans , Animals , BCG Vaccine , Nontuberculous Mycobacteria , Immunity, Cellular
10.
Scand J Immunol ; 73(2): 85-90, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21198748

ABSTRACT

We have previously reported a new receptor (NC-2) for natural cytotoxicity (NC) on murine leucocytes, identified by monoclonal antibody D9 (mAb D9). Pretreatment of mouse spleen cells with different concentrations of mAb D9 in vitro blocked NC against WEHI-164, whereas natural killing (NK) activity against YAC-1 was unaffected. This paper reports the immune surveillance against the growth of WEHI-164 tumour cells in mice by NC-2(+) Cells. The kinetics of in vivo reduction in NC activity were investigated by treating BALB/c and (CBA × C57BL/6) F1 mice with a single injection of 40 µg of mAb D9 and monitoring splenic NC activity by (51) Cr-release assay at intervals from 24 h to 3 weeks. Control mice were injected with OKT8 irrelevant antibody. Results showed a significant (P < 0.05) reduction in splenic NC activity within 24 h which persisted for up to 1 week. Similar results were also obtained when (CBA × C57BL/6) F1 mice were employed (P<0.001). In vivo tumour studies were undertaken to investigate the role of NC-2(+) cells in surveillance against tumour growth and metastasis of the WEHI-164 fibrosarcoma. When syngeneic BALB/c mice were injected with 40 µg of mAb D9 and then challenged with 5 × 10(5) WEHI-164 cells, results showed significantly increased growth rate of the transplanted WEHI-164 fibrosarcoma and tumour nodules in the lungs of animals, when compared to control mice with normal NC activity. Our data support an innate surveillance in metastasis and growth of WEHI-164 fibrosarcoma in mice.


Subject(s)
Fibrosarcoma/pathology , Lung Neoplasms/secondary , Animals , Cell Line, Tumor , Cell Proliferation , Female , Male , Mice , Neoplasm Transplantation
11.
J Pediatr Adolesc Gynecol ; 34(5): 662-665, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33989805

ABSTRACT

STUDY OBJECTIVE: Adolescent menstrual dysfunction (AMD) is a common cause of iron deficiency anemia and absences from school. The management of AMD with single- and double-dose desogestrel is largely on the basis of anecdotal evidence. Our aim was to describe the effectiveness and safety of both dosing strategies in our clinic cohort to help guide future management. DESIGN: Local service evaluation with retrospective analysis of clinic notes. SETTING: Adolescent gynecology clinic in a tertiary pediatric center in the North West of England. PARTICIPANTS: Adolescent girls (10-18 years of age) with AMD (n = 129). INTERVENTIONS: Single-dose (75 µg) desogestrel vs double-dose (150 µg) desogestrel. MAIN OUTCOME MEASURES: Prevalence of amenorrhea and light spotting, side effects, and discontinuation rates of both dosing regimens. RESULTS: Forty-three of 87 (49%) adolescent girls who started treatment with a double dose of desogestrel were amenorrheic/experienced light spotting, compared with 7/40 (18%) of girls who started treatment with a single dose (P = .001). Patients taking a double dose of desogestrel were less likely to discontinue overall (double: 45/89 [51%]; vs single: 35/40 [88%]; P < .001) and there was no evidence of an increase in nonbleeding side effects (double: 30/89 [34%]; vs single: 15/40 [38%]; P = .68). CONCLUSION: Our findings provide evidence that a double dose of desogestrel is associated with a higher prevalence of amenorrhea and light spotting compared with a single dose in adolescent girls with AMD. However, larger studies are needed to further inform clinical guidelines.


Subject(s)
Desogestrel , Metrorrhagia , Adolescent , Amenorrhea/chemically induced , Child , Desogestrel/adverse effects , Ethinyl Estradiol , Female , Humans , Retrospective Studies
12.
Vaccines (Basel) ; 9(4)2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33916180

ABSTRACT

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

13.
J Exp Med ; 154(2): 306-17, 1981 Aug 01.
Article in English | MEDLINE | ID: mdl-7264561

ABSTRACT

Mice were treated with the bone-seeking isotope, 89Sr, cyclophosphamide, and short-term lethal irradiation in vivo, and murine spleen cells are treated with anti-Nk-1.2 plus complement (C) in vitro. Fresh spleen cell suspensions from the above groups and from beige and neonatal mice were subsequently tested for natural killer (NK) cell activity against a panel of lymphoid and nonlymphoid tumor cell target. NK cell reactivities against YAC-1, MPC-11, and Cl.18 tumors were markedly and consistently reduced in (a) mice treated with 89Sr, (b) spleen cells treated with anti-Nk-1.2 plus C, and (c) C57BL/6 bg/bg mice. In contrast, NK activities against FLD-3 and WEHI-164.1 tumors were usually normal in mice treated with 89Sr, in beige mutant mice, and in spleen cells after treatment with anti-Nk-1.2 antibody and C. It appears, therefore, that two major groups of NK cells exist in fresh mouse spleen cells suspensions. NK-A cells are marrow dependent, Nk antigen positive, and deficient in beige mice; these lyse YAC-1, MPC-11, and Cl.18 tumors. NK-B cells, which are responsible for the lysis of WEHI-164.1 and FLD-3, are Nk antigen negative, marrow independent, and unaffected by the bg/bg mutation. Other features of NK-B cells, suggest that these NK cells, although they share the characteristics mentioned above, differ among themselves especially with respect to age of maturation and susceptibility to cyclophosphamide and total body irradiation. The NK-B group may therefore induce subsets that remain to be defined.


Subject(s)
Killer Cells, Natural/classification , Aging , Animals , Binding, Competitive , Cyclophosphamide/pharmacology , Killer Cells, Natural/radiation effects , Mice/genetics , Spleen/cytology , Strontium Radioisotopes
14.
J Exp Med ; 155(2): 557-73, 1982 Feb 01.
Article in English | MEDLINE | ID: mdl-6977009

ABSTRACT

The ultraviolet radiation-induced fibrosarcoma 1591 generally is rejected by normal syngeneic mice and only rarely exhibits progressive growth. We isolated five of these rare progressor tumors from normal animals to determine the selective pressures that had been exerted upon the parental tumor by normal immunocompetent hosts. We found that the variant tumor cell lines could neither induce nor be killed by tumor-specific lymphocytes, suggesting that selection had been exerted against tumor cells expressing the tumor-specific antigen. In contrast, no selection against natural killer cell activity or against nonspecific T cell-mediated immunity seems to have occurred because progressor tumor cells were highly sensitive to these types of effector cells and in fact induced these effector cells more effectively than did the parental tumor. Nude mice were found to be as capable as normal mice in generating natural killer activity in response to a challenge with progressor tumor cells, but they were unable to mount a nonspecific T lymphocyte response. This may account for the fact that the progressor tumors grew at a significantly faster rate in nude animals than in normal mice. Thus, our study shows that in this tumor system nonspecific T cell-mediated immunity may play a role in retarding tumor growth, but the absolute resistance of normal animals to progressive tumor growth critically depends upon the presence of T cell-mediated tumor-specific immunity. Furthermore, neither NK cells nor nonspecific cytotoxic T lymphocytes appear to play a role in immunoselection against this tumor in normal immunocompetent hosts.


Subject(s)
Cell Transformation, Neoplastic , Fibrosarcoma/genetics , Genetic Variation , Selection, Genetic , Animals , Antigens, Ly/immunology , Cytotoxicity, Immunologic , Female , Fibrosarcoma/immunology , Immune Sera/pharmacology , Immunity, Cellular , Mice , Mice, Inbred C3H , Mice, Nude , Neoplasm Regression, Spontaneous , Neoplasm Transplantation , T-Lymphocytes/immunology
15.
Am J Physiol Heart Circ Physiol ; 298(5): H1616-25, 2010 May.
Article in English | MEDLINE | ID: mdl-20228259

ABSTRACT

Sarcomere length (SL) is an important determinant and indicator of cardiac mechanical function; however, techniques for measuring SL in living, intact tissue are limited. Here, we present a technique that uses two-photon microscopy to directly image striations of living cells in cardioplegic conditions, both in situ (Langendorff-perfused rat hearts and ventricular tissue slices, stained with the fluorescent marker di-4-ANEPPS) and in vitro (acutely isolated rat ventricular myocytes). Software was developed to extract SL from two-photon fluorescence image sets while accounting for measurement errors associated with motion artifact in raster-scanned images and uncertainty of the cell angle relative to the imaging plane. Monte-Carlo simulations were used to guide analysis of SL measurements by determining error bounds as a function of measurement path length. The mode of the distribution of SL measurements in resting Langendorff-perfused heart is 1.95 mum (n = 167 measurements from N = 11 hearts) after correction for tissue orientation, which was significantly greater than that in isolated cells (1.71 mum, n = 346, N = 9 isolations) or ventricular slice preparations (1.79 mum, n = 79, N = 3 hearts) under our experimental conditions. Furthermore, we find that edema in arrested Langendorff-perfused heart is associated with a mean SL increase; this occurs as a function of time ex vivo and correlates with tissue volume changes determined by magnetic resonance imaging. Our results highlight that the proposed method can be used to monitor SL in living cells and that different experimental models from the same species may display significantly different SL values under otherwise comparable conditions, which has implications for experiment design, as well as comparison and interpretation of data.


Subject(s)
Microscopy, Fluorescence/methods , Myocytes, Cardiac/physiology , Myocytes, Cardiac/ultrastructure , Sarcomeres/physiology , Sarcomeres/ultrastructure , Algorithms , Animals , Cell Separation , Edema/pathology , Fluorescent Dyes , Heart Arrest, Induced , Image Processing, Computer-Assisted , In Vitro Techniques , Magnetic Resonance Imaging , Monte Carlo Method , Myocardial Contraction/physiology , Pyridinium Compounds , Rats , Rats, Sprague-Dawley
16.
J Evol Biol ; 23(3): 528-38, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20070459

ABSTRACT

Organismal fitness requires functional integration of nuclear and mitochondrial genomes. Structural and regulatory elements coevolve within lineages and several studies have found that interpopulation hybridization disrupts mitonuclear interactions. Because mitochondrial RNA polymerase (mtRPOL) plays key roles in both mitochondrial DNA (mtDNA) replication and transcription, the interaction between mtRPOL and coevolved regulatory sites in the mtDNA may be central to mitonuclear integration. Here, we generate interpopulation hybrids between divergent populations of the copepod Tigriopus californicus to obtain lines having different combinations of mtRPOL and mtDNA. Lines were scored for mtDNA copy number and ATP6 (mtDNA) gene expression. We find that there is a genotype-dependent negative association between mitochondrial transcriptional response and mtDNA copy number. We argue that an observed increase in mtDNA copy number and reduced mtDNA transcription in hybrids reflects the regulatory role of mtRPOL; depending on the mitonuclear genotype, hybridization may disrupt the normal balance between transcription and replication of the mitochondrial genome.


Subject(s)
Copepoda/genetics , DNA Copy Number Variations , DNA, Mitochondrial/metabolism , DNA-Directed RNA Polymerases/metabolism , Hybridization, Genetic , Animals , Copepoda/enzymology , DNA Replication , Genotype , Transcription, Genetic
17.
Int J Occup Environ Health ; 16(4): 451-7, 2010.
Article in English | MEDLINE | ID: mdl-21222388

ABSTRACT

Characterizing a process aerosol in the nanoscale beyond numeric concentration can assist in hazard assessment and in separating aerosolized process material from background aerosol. Size and size distribution, chemical composition, solubility, shape, and surface area may become important categorization parameters of exclusion/inclusion for purposes of exposure control. Various particle parameters are presented using examples from a process simulation. The process aerosol was composed of insoluble carbon particles plus environmental background constituents at an average air concentration of 2.76E+5 particles/cubic centimeter (p/cm3). Greater than 70% of the carbon particulate was blade-like in shape, 50% of which had a height dimension < or =100 nm. The equivalent spherical mobility diameter of 0.8% of the particulate was < or =100 nm in size. The carbon blades had a root-mean-square roughness of 75 nm and an average fractal dimension of 2.25. Obtaining these measures characterizes the aerosol and identifies parameters that may be important toxicologically.


Subject(s)
Aerosols/chemistry , Air Pollutants, Occupational/chemistry , Environmental Monitoring/methods , Nanoparticles/chemistry , Occupational Exposure/analysis , Particle Size
18.
Int J Occup Environ Health ; 16(4): 429-33, 2010.
Article in English | MEDLINE | ID: mdl-21222386

ABSTRACT

Deposition of particles in sampling lines may occur due to various physical forces. Particles in the nanoscale are not highly susceptible to inertial or sedimentary deposition, and electrical losses are reportedly controlled by using conductive tubing. Particle losses from diffusion affect size distribution and number concentration. Selectively removing the smallest particles has the effect of increasing the statistical measure of particle size-the geometric mean-while decreasing number concentration and geometric standard deviation. Quantification of losses is necessary to interpret or correct the data. Sample loss from a rigid graphitic or flexible Tygon tube attached to a scanning mobility particle sizer inlet was investigated during sampling at the Center for Nanophase Materials Sciences. Mean concentrations and particle size parameters determined from samples collected with and without sample inlet extensions were compared. Number concentration decreased and mean particle size increased for both tubing types at lengths of approximately 0.7 m.


Subject(s)
Environmental Monitoring , Nanoparticles/analysis , Environmental Monitoring/instrumentation , Particle Size
19.
Vaccine ; 38(45): 7156-7165, 2020 10 21.
Article in English | MEDLINE | ID: mdl-32978002

ABSTRACT

Although vaccination with BCG prevents disseminated forms of childhood tuberculosis (TB), it does not protect against pulmonary infection or Mycobacterium tuberculosis (Mtb) transmission. In this study, we generated a complete deletion mutant of the Mtb Esx-5 type VII secretion system (Mtb Δesx-5). Mtb Δesx-5 was highly attenuated and safe in immunocompromised mice. When tested as a vaccine candidate to boost BCG-primed immunity, Mtb Δesx-5 improved protection against highly virulent Mtb strains in the murine and guinea pig models of TB. Enhanced protection provided by heterologous BCG-prime plus Mtb Δesx-5 boost regimen was associated with increased pulmonary influx of central memory T cells (TCM), follicular helper T cells (TFH) and activated monocytes. Conversely, lower numbers of T cells expressing exhaustion markers were observed in vaccinated animals. Our results suggest that boosting BCG-primed immunity with Mtb Δesx-5 is a potential approach to improve protective immunity against Mtb. Further insight into the mechanism of action of this novel prime-boost approach is warranted.


Subject(s)
Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculosis , Type VII Secretion Systems , Animals , Antigens, Bacterial , BCG Vaccine , Guinea Pigs , Immunization, Secondary , Mice , Mycobacterium tuberculosis/genetics , Tuberculosis/prevention & control , Vaccination
20.
Br J Dermatol ; 161(6): 1270-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19747359

ABSTRACT

BACKGROUND: Studies have shown the benign to malignant ratio of excised pigmented skin lesions is suboptimal in primary care. OBJECTIVES: To assess the impact of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) on the management of suspicious pigmented skin lesions by primary care physicians. METHODS: A total of 63 primary care physicians were trained in the use of dermoscopy and SDDI (interventions) and then recruited pigmented lesions requiring biopsy or referral in routine care by naked eye examination. They were then given a dermatoscope and the option of a SDDI instrument, and change of diagnosis and management was assessed. RESULTS: Following the use of the interventions on 374 lesions a total of 163 lesions (43.6%) were excised or referred, representing a reduction of 56.4%. Of the 323 lesions confirmed to be benign, 118 (36.5%) were excised or referred, leading to a reduction of 63.5% (P < 0.0005) in those requiring excision or referral. The baseline naked eye examination benign to melanoma ratio was 9.5 : 1 which decreased to 3.5 : 1 after the diagnostic interventions (P < 0.0005). Of the 42 malignant lesions included in the study (34 melanoma, six pigmented basal cell carcinoma and two Bowen disease) only one in situ melanoma was incorrectly managed (patient to return if changes occur) resulting in the correct management of 97.6% and 97.1% of malignant pigmented lesions and melanoma, respectively. CONCLUSIONS: In a primary care setting the combination of dermoscopy and short-term SDDI reduces the excision or referral of benign pigmented lesions by more than half while nearly doubling the sensitivity for the diagnosis of melanoma.


Subject(s)
Dermoscopy/methods , Early Detection of Cancer/methods , Melanoma/diagnosis , Physical Examination/methods , Skin Neoplasms/diagnosis , Clinical Competence , Family Practice/education , Family Practice/statistics & numerical data , Female , Humans , Male , Melanoma/surgery , Mucous Membrane , Observer Variation , Referral and Consultation/statistics & numerical data , Sensitivity and Specificity , Skin Neoplasms/surgery , Western Australia
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