Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices

Objective The aim of this study was to investigate how head and neck squamous cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment within a bespoke microfluidic device respond to radiation treatment. Study Design Feasibility study. Setting Tertiary referral center. Subjects and Methods Thirty-five patients with HNSCC were recruited, and liver tissue from 5 Wistar rats was obtained. A microfluidic device was used to maintain the tissue biopsy samples in a viable state. Rat liver was used to optimize the methodology. HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2 metastatic cervical lymph nodes were also obtained. Irradiation consisted of single doses of between 2 Gy and 40 Gy and a fractionated course of 5×2 Gy. Cell death was assessed in the tissue effluent using the soluble markers lactate dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical detection of cleaved cytokeratin18 (M30 antibody). Results A significant surge in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in HNSCC, it was seen after 40 Gy compared with the control. There was no significant difference in cytochrome c release after 5 Gy or 10 Gy. M30 demonstrated a dose-dependent increase in apoptotic index for a given increase in single-dose radiotherapy. There was a significant increase in apoptotic index between 1×2 Gy and 5×2 Gy. Conclusion M30 is a superior method compared with soluble markers in detecting low-dose radiation-induced cell death. This microfluidic technique can be used to assess radiation-induced cell death in HNSCC and therefore has the potential to be used to predict radiation response

Target product profiles for protecting against outdoor malaria transmission.

BACKGROUND\ud \ud Long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have decimated malaria transmission by killing indoor-feeding mosquitoes. However, complete elimination of malaria transmission with these proven methods is confounded by vectors that evade pesticide contact by feeding outdoors.\ud \ud METHODS\ud \ud For any assumed level of indoor coverage and personal protective efficacy with insecticidal products, process-explicit malaria transmission models suggest that insecticides that repel mosquitoes will achieve less impact upon transmission than those that kill them outright. Here such models are extended to explore how outdoor use of products containing either contact toxins or spatial repellents might augment or attenuate impact of high indoor coverage of LLINs relying primarily upon contact toxicity.\ud \ud RESULTS\ud \ud LLIN impact could be dramatically enhanced by high coverage with spatial repellents conferring near-complete personal protection, but only if combined indoor use of both measures can be avoided where vectors persist that prefer feeding indoors upon humans. While very high levels of coverage and efficacy will be required for spatial repellents to substantially augment the impact of LLINs or IRS, these ambitious targets may well be at least as practically achievable as the lower requirements for equivalent impact using contact insecticides.\ud \ud CONCLUSIONS\ud \ud Vapour-phase repellents may be more acceptable, practical and effective than contact insecticides for preventing outdoor malaria transmission because they need not be applied to skin or clothing and may protect multiple occupants of spaces outside of treatable structures such as nets or houses

The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation

Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation. In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation. Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre-existing chiral centres that are proximal to the reactive site. Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized. Here we report the use of a double stereoablative enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F (ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product

Democratic Teacher Education Practices

[Living reference work entry] This entry provides an insight into the turbulent and recently disappointing events in the history of Design and Technology (D&T) teacher education in England over the last 150 years. It is a complex journey that needs to include a review of the generic history of teacher education in England, the differing educational needs of children, the changing role of D&T as a school curriculum subject, the requirements for an appropriately trained workforce to meet the economic needs of the country, and how various government educational initiatives and interventions (Gillard 2018) have affected how teachers in general and D&T teachers in particular have been and still are trained today. All these factors are inseparably intertwined. Therefore, this entry discusses them all together in chronological date order

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

A Systematic Review of Mosquito Coils and Passive Emanators: Defining Recommendations for Spatial Repellency Testing Methodologies.

Mosquito coils, vaporizer mats and emanators confer protection against mosquito bites through the spatial action of emanated vapor or airborne pyrethroid particles. These products dominate the pest control market; therefore, it is vital to characterize mosquito responses elicited by the chemical actives and their potential for disease prevention. The aim of this review was to determine effects of mosquito coils and emanators on mosquito responses that reduce human-vector contact and to propose scientific consensus on terminologies and methodologies used for evaluation of product formats that could contain spatial chemical actives, including indoor residual spraying (IRS), long lasting insecticide treated nets (LLINs) and insecticide treated materials (ITMs). PubMed, (National Centre for Biotechnology Information (NCBI), U.S. National Library of Medicine, NIH), MEDLINE, LILAC, Cochrane library, IBECS and Armed Forces Pest Management Board Literature Retrieval System search engines were used to identify studies of pyrethroid based coils and emanators with key-words "Mosquito coils" "Mosquito emanators" and "Spatial repellents". It was concluded that there is need to improve statistical reporting of studies, and reach consensus in the methodologies and terminologies used through standardized testing guidelines. Despite differing evaluation methodologies, data showed that coils and emanators induce mortality, deterrence, repellency as well as reduce the ability of mosquitoes to feed on humans. Available data on efficacy outdoors, dose-response relationships and effective distance of coils and emanators is inadequate for developing a target product profile (TPP), which will be required for such chemicals before optimized implementation can occur for maximum benefits in disease control

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

Giant Persistent Photoconductivity of the WO3 Nanowires in Vacuum Condition

A giant persistent photoconductivity (PPC) phenomenon has been observed in vacuum condition based on a single WO3 nanowire and presents some interesting results in the experiments. With the decay time lasting for 1 × 104 s, no obvious current change can be found in vacuum, and a decreasing current can be only observed in air condition. When the WO3 nanowires were coated with 200 nm SiO2 layer, the photoresponse almost disappeared. And the high bias and high electric field effect could not reduce the current in vacuum condition. These results show that the photoconductivity of WO3 nanowires is mainly related to the oxygen adsorption and desorption, and the semiconductor photoconductivity properties are very weak. The giant PPC effect in vacuum condition was caused by the absence of oxygen molecular. And the thermal effect combining with oxygen re-adsorption can reduce the intensity of PPC