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PURPOSE OF REVIEW: The present investigation evaluated integration of novel medication technology to enhance treatment options, while improving patient outcomes in acute pain management. In this regard, we focused on determining the role of development and utilization of cutting-edge pharmaceutical advancements, such as targeted drug delivery systems, as well as non-pharmacologic interventions in addressing acute pain states. Further research in this area is warranted related to the need for increased patient comfort and reduced adverse effects. RECENT FINDINGS: Recent innovations and techniques are discussed including pharmacologic drugs targeting sodium and calcium channels, peptide-based pharmacologic drugs, and non-medicinal methods of alleviating pain such as soothing music or virtual reality. The present investigation included review of current literature on the application of these innovative technologies, analyzing mechanisms of action, pharmacokinetics, and clinical effectiveness. Our study also investigated the potential benefits in terms of pain relief, reduced side effects, and improved patient adherence. The research critically examines the challenges and considerations associated with implementing these technologies in acute pain management, considering factors like cost, accessibility, and regulatory aspects. Additionally, case studies and clinical trials are highlighted which demonstrate practical implications of these novel medication technologies in real-world scenarios. The findings aim to provide healthcare professionals with a comprehensive understanding of the evolving landscape in acute pain management while guiding future research and clinical practices toward optimizing their use in enhancing patient care.
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The lateral circumflex femoral artery (LCFA), a branch of the deep femoral artery (DFA), supplies the muscular and fascial anatomy of the anterior thigh. An undocumented variation of the LCFA was discovered during a dissection of the lower extremities. The LCFA is a vital vessel that can be used in coronary artery bypass grafts (CABGs) and reconstructive and bypass surgical procedures. On the other hand, the LCFA is susceptible to iatrogenic damage during surgeries involving the hip joint and procedures such as femoral nerve blocks. Knowledge of variations in the origin and course of the LFCA, like many other anatomical structures, is an important concept that physicians and health care providers must be aware of when performing anterior thigh procedures. This case report shows an interesting duplication of the LCFA, the first originating superiorly from the common femoral artery (CFA) and the second from the deep femoral artery (DFA) inferiorly. Both LCFAs exhibited typical trifurcation into ascending, descending, and transverse branches.
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The successful rehabilitation and release of raptor chicks can be challenging, especially when the chicks are still in the post-fledging dependency period. Here, we report on a recently fledged powerful owl chick that was held in care for 33 days before being successfully reunited with its parents. We document the steps undertaken during the entire process from collection from the wild to post-release monitoring and recommend clinical procedures for treatment of raptors entering veterinary facilities. Success of this rehabilitation was facilitated by early care and treatment for potential rodenticide poisoning, as well as the integration of citizen scientists monitoring the family unit in the field while the chick was in care and during the post-release period. Given the emerging evidence of widespread rodenticide poisoning in raptors both in Australia and globally, it is critical to suspect all raptors may have been exposed to anticoagulant rodenticides and commence treatment with vitamin K immediately. Routine treatment for rodenticides early increases the probability of successful recovery post-trauma as well as reducing the time in treatment as much as possible.
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Rapaces , Rodenticidas , Estrigiformes , Animales , Anticoagulantes , PollosRESUMEN
Respiratory infections are common in children, and there is a need for user-friendly collection methods. Here, we performed the first human subjects study using the CandyCollect device, a lollipop-inspired saliva collection device .We showed that the CandyCollect device can be used to collect salivary bacteria from healthy adults using Streptococcus mutans and Staphylococcus aureus as proof-of-concept commensal bacteria. We enrolled healthy adults in a nationwide (USA) remote study in which participants were sent study packages containing CandyCollect devices and traditional commercially available oral swabs and spit tubes. Participants sampled themselves at home, completed usability and user preference surveys, and mailed the samples back to our laboratory for analysis by qPCR. Our results showed that for participants in which a given bacterium (S. mutans or S. aureus) was detected in one or both of the commercially available methods (oral swab and/or spit tubes), CandyCollect devices had a 100% concordance with the positive result (n = 14 participants). Furthermore, the CandyCollect device was ranked the highest preference sampling method among the three sampling methods by 26 participants surveyed (combining survey results across two enrollment groups). We also showed that the CandyCollect device has a shelf life of up to 1 year at room temperature, a storage period that is convenient for clinics or patients to keep the CandyCollect device and use it any time. Taken together, we have demonstrated that the CandyCollect is a user-friendly saliva collection tool that has the potential to be incorporated into diagnostic assays in clinic visits and telemedicine.
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Saliva , Staphylococcus aureus , Niño , Humanos , Adulto , Saliva/microbiología , Manejo de Especímenes/métodos , Streptococcus mutans , LaboratoriosRESUMEN
Toxic species of the dinoflagellate genus Dinophysis can produce diarrheic toxins including okadaic acid (OA) and dinophysistoxins (DTXs), and the non-diarrheic pectenotoxins (PTXs). Okadaic acid and DTXs cause diarrheic shellfish poisoning (DSP) in human consumers, and also cause cytotoxic, immunotoxic and genotoxic effects in a variety of mollusks and fishes at different life stages in vitro. The possible effects of co-produced PTXs or live cells of Dinophysis to aquatic organisms, however, are less understood. Effects on an early life stage of sheepshead minnow (Cyprinodon variegatus), a common finfish in eastern USA estuaries, were evaluated using a 96-h toxicity bioassay. Three-week old larvae were exposed to PTX2 concentrations from 50 to 4000 nM, live Dinophysis acuminata culture (strain DAVA01), live cells resuspended in clean medium or culture filtrate. This D. acuminata strain produced mainly intracellular PTX2 (≈ 21 pg cell-1), with much lower levels of OA and dinophysistoxin-1. No mortality or gill damages were observed in larvae exposed to D. acuminata (from 5 to 5500 cells mL-1), resuspended cells and culture filtrate. However, exposure to purified PTX2 at intermediate to high concentrations (from 250 to 4000 nM) resulted in 8 to 100% mortality after 96 h (24-h LC50 of 1231 nM). Histopathology and transmission electron microscopy of fish exposed to intermediate to high PTX2 concentrations revealed important gill damage, including intercellular edema, necrosis and sloughing of gill respiratory epithelia, and damage to the osmoregulatory epithelium, including hypertrophy, proliferation, redistribution and necrosis of chloride cells. Tissue damage in gills is likely caused by the interaction of PTX2 with the actin cytoskeleton of the affected gill epithelia. Overall, the severe gill pathology observed following the PTX2 exposure suggested death was due to loss of respiratory and osmoregulatory functions in C. variegatus larvae.
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Cyprinidae , Dinoflagelados , Peces Killi , Contaminantes Químicos del Agua , Animales , Humanos , Ácido Ocadaico , Toxinas Marinas/toxicidad , Larva , Contaminantes Químicos del Agua/toxicidadRESUMEN
Respiratory infections are common in children, and there is a need for user-friendly collection methods. Here, we performed the first human subjects study using the CandyCollect device, a lollipop inspired saliva collection device. 1 We showed the CandyCollect device can be used to collect salivary bacteria from healthy adults using Streptococcus mutans and Staphylococcus aureus as proof-of-concept commensal bacteria. We enrolled healthy adults in a nationwide (USA) remote study in which participants were sent study packages containing CandyCollect devices and traditional commercially available oral swabs and spit tubes. Participants sampled themselves at home, completed usability and user preference surveys, and mailed the samples back to our laboratory for analysis by qPCR. Our results showed that for participants in which a given bacterium ( S. mutans or S. aureus ) was detected in one or both of the commercially available methods (oral swab and/or spit tubes), CandyCollect devices had a 100% concordance with the positive result (n=14 participants). Furthermore, the CandyCollect device was ranked the highest preference sampling method among the three sampling methods by 26 participants surveyed (combining survey results across two enrollment groups). We also showed that the CandyCollect device has a shelf life of up to 1 year at room temperature, a storage period that is convenient for clinics or patients to keep the CandyCollect device and use it any time. Taken together, we have demonstrated that the CandyCollect is a user-friendly saliva collection tool that has the potential to be incorporated into diagnostic assays in clinic visits and telemedicine.
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BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.
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We describe a 47-year-old non-atopic woman, working as a spray painter in a tannery for 23 years, with a 16-year history of cutaneous symptoms and a subsequent 2-year history of asthmatic symptoms after exposure to aerosol and vapour of polyfunctional aziridine (PFA) at work. To confirm the occupational origin of the dermatitis and asthma we performed a skin prick test with PFA and a specific inhalation challenge (SIC) with PFA. Prick test with PFA elicited an immediate positive skin reaction. She developed an immediate asthmatic reaction upon SIC with PFA. The onset of occupational dermatitis before asthma is consistent with the hypothesis that the sensitization to PFA was triggered in the skin. The observation that the reactions elicited in skin and airways upon exposure to PFA exhibited the same time course, suggests a similar mechanism at both sites. Thus, the avoidance of both skin and airway exposure to PFA should be recommended in workplace hygiene practice.
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Asma Ocupacional/inducido químicamente , Aziridinas/efectos adversos , Dermatitis Profesional/etiología , Asma Ocupacional/etiología , Pruebas de Provocación Bronquial , Dermatitis por Contacto/etiología , Femenino , Humanos , Persona de Mediana Edad , Pintura/efectos adversosRESUMEN
In this work, five Crassulacean Acid Metabolism (CAM) species from the five different genera (Agave, Ananas, Euphorbia, Kalanchoe, and Opuntia) were selected as alternative feedstocks and their biochemical methane potentials (BMP) were investigated. Batch assays were performed using sludge and rumen fluid as inocula under uncontrolled pH and at mesophilic temperature (39⯰C). Mean methane yields from the CAM plants inoculated with AD sludge ranged from 281 to 382â¯ml/gVS. These values were not significantly different from the methane yield obtained from maize, a feedstock for biomethane and volatile fatty acid (VFA), suggesting that CAM plants may be viable as bioenergy crops on poor-quality soils in areas with low rainfall that are unsuitable for cultivation of food crops.
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Agave , Aguas del Alcantarillado , Anaerobiosis , Animales , Reactores Biológicos , Ácidos Grasos Volátiles , MetanoRESUMEN
Gene editing following designer nuclease cleavage in the presence of a DNA donor template can revert mutations in disease-causing genes. For optimal benefit, reversion of the point mutation in HBB leading to sickle cell disease (SCD) would permit precise homology-directed repair (HDR) while concurrently limiting on-target non-homologous end joining (NHEJ)-based HBB disruption. In this study, we directly compared the relative efficiency of co-delivery of a novel CRISPR/Cas9 ribonucleoprotein targeting HBB in association with recombinant adeno-associated virus 6 (rAAV6) versus single-stranded oligodeoxynucleotides (ssODNs) to introduce the sickle mutation (GTC or GTG; encoding E6V) or a silent change (GAA; encoding E6optE) in human CD34+ mobilized peripheral blood stem cells (mPBSCs) derived from healthy donors. In vitro, rAAV6 outperformed ssODN donor template delivery and mediated greater HDR correction, leading to both higher HDR rates and a higher HDR:NHEJ ratio. In contrast, at 12-14 weeks post-transplant into recipient, immunodeficient, NOD, B6, SCID Il2rγ-/- Kit(W41/W41) (NBSGW) mice, a â¼6-fold higher proportion of ssODN-modified cells persisted in vivo compared to recipients of rAAV6-modified mPBSCs. Together, our findings highlight that methodology for donor template delivery markedly impacts long-term persistence of HBB gene-modified mPBSCs, and they suggest that the ssODN platform is likely to be most amenable to direct clinical translation.
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OBJECTIVE: To examine the prevalence and magnitude of chronic lung disease (CLD) and its association with empiric anti-tuberculosis treatment (due to lack of bacteriologic confirmation) among recurrent tuberculosis (TB) survivors in a human immunodeficiency virus (HIV) prevalent setting. METHODS: Prospective cohort study of retreatment TB survivors in Harare, Zimbabwe. At median follow-up of 2 years post-treatment initiation, we characterized mortality, respiratory impairment, and mental health. RESULTS: Among 175 retreatment TB survivors, 65% of whom were HIV-positive and 21% had been empirically treated, multiparameter CLD was noted at follow-up among 14% of patients (95%CI 9.0-19.7), with a six-fold increase in age-adjusted death in the first year following treatment completion. Empirically treated TB (relative risk [RR] 3.4, 95%CI 1.4-8.3) was associated with CLD, as was the number of previous anti-tuberculosis treatment courses in dose-dependent fashion (three vs. one, RR 6.2, 95%CI 1.7-22.1). Among retreatment TB survivors, 33% (95%CI 26.0-40.1) had persistent respiratory symptoms (Chronic Obstructive Pulmonary Disease Assessment Test score î¶10); 26% (95%CI 19.8-33.0) significant deficits in exercise capacity (median incremental shuttle walk test distance, 550 m; Q1-Q3 440-730 m); 83% (95%CI 75.7-89.7) residual radiographic abnormalities on chest X-ray; 12% (95%CI 6.6-16.1%) moderate-to-severe obstruction on spirometry; and 13% (95%CI 7.6-17.5%) major depression. CONCLUSIONS: Despite successful treatment, retreatment TB survivors retain a substantial risk of morbidity and mortality.
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Antituberculosos/administración & dosificación , Infecciones por VIH/epidemiología , Enfermedades Pulmonares/epidemiología , Tuberculosis/epidemiología , Adulto , Enfermedad Crónica , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Pulmonares/etiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Recurrencia , Retratamiento , Sobrevivientes , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , Zimbabwe/epidemiologíaRESUMEN
We report channel-resolved measurements of the anharmonic coupling of the coherent A_{1g} phonon in photoexcited bismuth to pairs of high wave vector acoustic phonons. The decay of a coherent phonon can be understood as a parametric resonance process whereby the atomic displacement periodically modulates the frequency of a broad continuum of modes. This coupling drives temporal oscillations in the phonon mean-square displacements at the A_{1g} frequency that are observed across the Brillouin zone by femtosecond x-ray diffuse scattering. We extract anharmonic coupling constants between the A_{1g} and several representative decay channels that are within an order of magnitude of density functional perturbation theory calculations.
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We present an extensive study of rehomogenized olivine-hosted melt inclusions, olivine phenocrysts, and chromian spinel inclusions to explore the link between geodynamic conditions and the origin and composition of Pliocene-Quaternary intraplate magmatism in Anatolia at Kula, Ceyhan-Osmaniye, and Karacadag. Exceptional compositional variability of these products reveals early and incomplete mixing of distinct parental melts in each volcanic center, reflecting asthenospheric and lithospheric mantle sources. The studied primitive magmas consist of (1) two variably enriched ocean island basalt (OIB)-type melts in Kula; (2) both OIB-type and plume mid-ocean ridge basalt (P-MORB)-like melts beneath Toprakkale and Üçtepeler (Ceyhan-Osmaniye); and (3) two variably enriched OIB-type melts beneath Karacadag. Estimated conditions of primary melt generation are 23-9 kbar, 75-30 km, and 1415-1215 °C for Kula; 28-19 kbar, 90-65 km, and 1430-1350 °C for Toprakkale; 23-18 kbar, 75-60 km, and 1400-1355 °C for Üçtepeler; and 35-27 kbar, 115-90 km, and 1530-1455 °C for Karacadag, the deepest levels of which correspond to the depth of the lithosphere-asthenosphere boundary in all regions. Although magma ascent was likely facilitated by local deformation structures, recent Anatolian intraplate magmatism seems to be triggered by large-scale mantle flow that also affects the wider Arabian and North African regions. We infer that these volcanics form part of a much wider Arabian-North African intraplate volcanic province, which was able to invade the Anatolian upper plate through slab gaps.
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BACKGROUND: Isocyanate-induced asthmatic reactions are associated with delayed increase in fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (FeNO50), a biomarker of airway inflammation. The time course of FeNO increase is compatible with the activation of NO synthase, but the origin of NO production in the lung is undetermined. OBJECTIVE: The aim of this study was to define the dynamics of airway and alveolar NO during specific inhalation challenge (SIC) with isocyanates and the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase. METHODS: Spirometry, exhaled NO parameters (FeNO50, bronchial wall NO concentration, NO airway diffusing capacity, NO flux to luminal space, alveolar NO) and ADMA levels in exhaled breath condensate were measured before and at intervals up to 24 h after exposure to isocyanates. The results were compared between 17 SIC-positive and eight SIC-negative subjects. RESULTS: A significant FeNO50 increase in SIC-positive subjects was detected 24 h after exposure and was associated with the augmented NO flux from airway wall to the lumen, whereas airway NO diffusion and alveolar NO were not affected. The changes in NO dynamics were specific for the subjects who developed an asthmatic reaction, but were independent from the pattern and magnitude of bronchoconstriction. There was no evidence that exhaled NO is modulated by the changes in ADMA concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Because isocyanate-induced increase in FeNO50 was almost exclusively determined by the increase in NO flux, the use of FeNO50 appears adequate to monitor the exhaled NO dynamics during SIC. FeNO50 measurement may provide additional information to spirometry, because bronchoconstriction and airway inflammatory responses are dissociated.
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Asma/diagnóstico , Asma/etiología , Espiración , Isocianatos/efectos adversos , Óxido Nítrico , Adulto , Biomarcadores , Pruebas Respiratorias , Pruebas de Provocación Bronquial , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de TiempoRESUMEN
Anaerobic digestion of plant biomass to hydrocarbons could play a major part in meeting the needs of a modern low carbon society, but the cost reductions needed to make it an economically viable technology have been slower to arrive than in other renewable technologies. This is notwithstanding the observation that ruminants carry out the rate limiting hydrolysis step up to 30 times faster than an AD plant, and that bio-mimicry of ruminants could be an important source of innovation. This paper examines a number of factors which may, by focusing emphasis on the physical and chemical environment within cellulolytic biofilms, help accelerate development in the arena. It examines the process of cellulolysis from the perspective of a bacterium attached within a biofilm to a piece of insoluble cellulosic substrate to illustrate the extent of chemical heterogeneity that exists in the film, and between the film and the supernatant, and how this might control the rate of cellulolysis. It suggests several strategies used by ruminants to manage this heterogeneity that may be significant contributors to their effectiveness, and could provide a useful guide to more effective anaerobic digestion.
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Biopelículas , Rumiantes , Anaerobiosis , Animales , Biomasa , Hidrólisis , PlantasRESUMEN
BACKGROUND: Patients at elevated risk of drug-resistant tuberculosis (TB) are prioritized for Xpert(®) MTB/RIF testing; however, the clinical usefulness of the test in this population is understudied. DESIGN: From November 2011 to June 2014, consecutive out-patients with a history of previous TB in high-density suburbs of Harare, Zimbabwe, were tested using Xpert, solid and liquid culture, and the microscopic observation drug susceptibility assay. Diagnostic accuracy for rifampin (RMP) resistance and time to initiation of second-line regimens were ascertained. The rpoB gene was sequenced in cases with culture-confirmed RMP resistance and genotypic susceptibility. RESULTS: Among 352 retreatment patients, 71 (20%) were RMP-resistant, 98 (28%) RMP-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative. Xpert had a sensitivity of 86% (95%CI 75-93) and a specificity of 98% (95%CI 92-100) for RMP-resistant TB. The positive predictive value of Xpert-determined RMP resistance for multidrug-resistant TB (MDR-TB) was 82% (95%CI 70-91). Of 71 (83%) participants, 59 initiated treatment with second-line drugs, with a median time to treatment initiation of 18 days (IQR 10-44). CONCLUSION: The diagnostic accuracy of Xpert for RMP resistance is high, although the predictive value for MDR-TB was lower than anticipated. Xpert allows for faster initiation of second-line treatment than culture-based drug susceptibility testing under programmatic conditions.
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Antituberculosos/uso terapéutico , Proteínas Bacterianas/genética , Análisis Mutacional de ADN , ARN Polimerasas Dirigidas por ADN/genética , Farmacorresistencia Bacteriana/genética , Técnicas de Diagnóstico Molecular , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Rifampin/uso terapéutico , Tiempo de Tratamiento , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Retratamiento , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis/microbiología , ZimbabweRESUMEN
The thermal conductivity of solid biomass fuels is useful information in the investigation of biomass combustion behavior and the development of modeling especially in the context of large scale power generation. There are little published data on the thermal conductivity of certain types of biomass such as wheat straw, miscanthus, and torrefied woods. Much published data on wood is in the context of bulk materials. A method for determining the thermal conductivities of small particles of biomass fuels has been developed using a custom built test apparatus. Fourteen different samples of various solid biomass fuel were processed to form a homogenized pellet for analysis. The thermal conductivities of the pelletized materials were determined and compared against each other and to existing data.
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Biomedical innovations are unlikely to provide effective and ethical tuberculosis (TB) control measures without complementary social science research. However, a strong interest in interdisciplinary work is often undermined by differences in language and concepts specific to each disciplinary approach. Accordingly, biological and social scientists need to learn how to communicate with each other. This article will outline key concepts relating to TB from medical anthropology and health sociology. Distilling these concepts in an introductory framework is intended to make this material accessible to researchers in laboratory, clinical and fieldwork settings, as well as to encourage more social scientists to engage with TB research among target groups critical for successful programmatic interventions. For pedagogical purposes, the relevant concepts are grouped into three categories: 1) structures and settings, which includes overarching themes such as syndemics, local biologies, medicalisation, structural violence and surveillance; 2) practices and processes, encompassing gender, stigma, taboo, and victim blaming; and 3) experience and enculturation, which includes illness narratives, biographical disruption and dynamic nominalism. By helping to navigate this literature, we hope to foster more cross-disciplinary conversations between qualitative and quantitative researchers. TB, a quintessential social disease, will be controlled more effectively using a multistranded research approach.