Applied Radiation and Isotopes Monte Carlo Verification of Output Correction Factors for a TrueBeam STx linac

The recent publication of the new code of practice IEAA/AAPM TRS-483 introduces the use of output correction factors to correct the changes in detector response in relative dosimetry of small photon beams. In TRS-483, average correction factors are reported for several detectors at 6 and 10 MV with and without attening. These correction factors were determined by Monte Carlo simulation or experimental measurements using several linacs of di erent brands and vendors. The goal of this work was to validate the output correction factors reported in TRS-483 for a 6 MV (with and without attening lter) of a TrueBeam STx® linac with Monte Carlo simulation for four radiation detectors employed in the dosimetry of small photon beams and whose output correction factors were determined using di erent radiation source than TrueBeam STx®: PTW®31010, PTW®31016, IBA®CC-01, and IBA®SFD. The results show that Monte Carlo calculated output factors, and those reported in the code of practice TRS-483 fully agree within 1%. The use of generic correction factors for a TrueBeam STx® and the detectors studied in this work is adequate for small dosimetry static beams within the uncertainties of Monte Carlo calculations and output correction factors reported in TRS-483. Key words: TRS-483, Monte Carlo simulation, output correction factors, detector model, Phase Space File, Latent Varianc

Fairness and Bias in Algorithmic Hiring

Employers are adopting algorithmic hiring technology throughout the recruitment pipeline. Algorithmic fairness is especially applicable in this domain due to its high stakes and structural inequalities. Unfortunately, most work in this space provides partial treatment, often constrained by two competing narratives, optimistically focused on replacing biased recruiter decisions or pessimistically pointing to the automation of discrimination. Whether, and more importantly what types of, algorithmic hiring can be less biased and more beneficial to society than low-tech alternatives currently remains unanswered, to the detriment of trustworthiness. This multidisciplinary survey caters to practitioners and researchers with a balanced and integrated coverage of systems, biases, measures, mitigation strategies, datasets, and legal aspects of algorithmic hiring and fairness. Our work supports a contextualized understanding and governance of this technology by highlighting current opportunities and limitations, providing recommendations for future work to ensure shared benefits for all stakeholders

Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae

Bioactivity-directed fractionation of the organic extracts of two filamentous fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the Mycosynthetix library, led to the isolation of a new dimeric epipolythiodioxopiperazine alkaloid, verticillin H (1), along with six related analogues, Sch 52900 (2), verticillin A (3), gliocladicillin C (4), Sch 52901 (5), 11'-deoxyverticillin A (6), and gliocladicillin A (7). The structures of compounds 1–7 were determined by extensive NMR and HRMS analyses, as well as by comparisons to the literature. All compounds (1–7) were evaluated for cytotoxicity against a panel of human cancer cell lines, displaying IC50 values ranging from 1.2 µM to 10 nM. Compounds 1–5 were examined for activity in the NF-?B assay, where compounds 2 and 3 revealed activity in the sub-micromolar range. Additionally, compounds 1, 3, and 4 were tested for EGFR inhibition using an enzymatic assay, while compound 3 was examined against an overexpressing EGFR+ve cancer cell line

Heat and mass transfer behaviours of building materials and structures

Heat storage as a means to respond to the requirements for improved energy efficiency motivated this study. The objective was to evaluate the impact of thermal energy storage systems in dwellings under Mexican climatic conditions. In the first part of this work thermal behaviors of adobe traditional architecture is discussed; in the second part a latent heat storage system using phase change materials (PCMs) is proposed and assessed. The high thermal mass structural elements of adobe traditional architecture have been charactefted as heat wave modulators. Nevertheless, the moisture content in these structures also plays a significant role as a means for heat storage and potentially enhancing thermal lag. The objective of this part of the study was to assess the scope of existing coupled heat and mass transport models regarding water contained latent heat storage on porous structures. The significant contribution of latent heat storage recognized in adobe structures, led to the study of a solar-thermal storage system using (PCMs). The objective of this part of the study was twofold: 1) Enhance the existing computational models on the Stephan problem by considering the effect of regional variations (weather conditions imposed) on the boundary conditions. 2) Evaluate the impact of the solar-thermal system proposed when applied in dwellings in view of regional variations under Mexican weather conditions. Solar-thermal storage systems independent of the structure offer the possibility to be applied to existing buildings as well as new constructions. The proposal is a storage element that constitutes internal blinds in windows. The computational model of the Stephan problem was solved with the enthalpy method. Simulations were run under different sets of climatic conditions. For the first time the main factors for promoting system's optimisation, when gathered in a single comparison study, provided a more general insight on system's performance. Experimental work was also carried out regarding the charging of the heat storage unit by heat gains other than direct radiation, and the storage unit's performance as insulator. A large-scale solar simulator was constructed. Statistical analysis of experimental results showed interesting findings including: The important role that internal heat gains play on the charging of the latent heat storage unit proposed. A larger effect on the discharging ratio was found with lower air temperatures than with faster air flow rates. The faster discharging rate tests also released slightly more energy. PCM volume was found to be the most critical factor on system performance. The importance of providing the means to discharge the total quantity of heat stored was pointed out. For the cooling mode, elements to enhance discharging might be required. For system control, thermal insulation was found to be an effective measure when the discharging is required to occur over a longer period. The multiple PCM unit was found to be more efficient during the charging process (storing more energy) than units containing a single PCM. Nevertheless the single PCM unit performed better for cooling than the multiple PCM unit. The question was raised as to what extent PCM thermal conductivity actually influences system's performance. The thermal storage system proposed in this study reduced the heating system energy consumption requirements for an experimental room by 28.6%.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

High-Resolution MS, MS/MS, and UV Database of Fungal Secondary Metabolites as a Dereplication Protocol for Bioactive Natural Products

A major problem in the discovery of new biologically active compounds from natural products is the reisolation of known compounds. Such reisolations waste time and resources, distracting chemists from more promising leads. To address this problem, dereplication strategies are needed that enable crude extracts to be screened for the presence of known compounds before isolation efforts are initiated. In a project to identify anticancer drug leads from filamentous fungi, a significant dereplication challenge arises, as the taxonomy of the source materials is rarely known, and, thus, the literature cannot be probed to identify likely known compounds. An ultraperformance liquid chromatography–photodiode array–high-resolution tandem mass spectrometric (UPLC-PDA-HRMS-MS/MS) method was developed for dereplication of fungal secondary metabolites in crude culture extracts. A database was constructed by recording HRMS and MS/MS spectra of fungal metabolites, utilizing both positive- and negative-ionization modes. Additional details, such as UV-absorption maxima and retention times, were also recorded. Small-scale cultures that showed cytotoxic activities were dereplicated before engaging in the scale-up or purification processes. Using these methods, approximately 50% of the cytotoxic extracts could be eliminated from further study after the confident identification of known compounds. The specific attributes of this dereplication methodology include a focus on bioactive secondary metabolites from fungi, the use of a 10 min chromatographic method, and the inclusion of both HRMS and MS/MS data

Peptaibols, Tetramic Acid Derivatives, Isocoumarins, and Sesquiterpenes from a Bionectria sp. (MSX 47401)

An extract of the filamentous fungus Bionectria sp. (MSX 47401) showed both promising cytotoxic activity (>90% inhibition of H460 cell growth at 20 µg/mL) and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). A bioactivity-directed fractionation study yielded one new peptaibol (1) and one new tetramic acid derivative (2), and the fungus biosynthesized diverse secondary metabolites with mannose-derived units. Five known compounds were also isolated: clonostachin (3), virgineone (4), virgineone aglycone (5), AGI-7 (6), and 5,6-dihydroxybisabolol (7). Compounds 5 and 7 have not been described previously from natural sources. Compound 1 represents the second member of the peptaibol structural class that contains an ester-linked sugar alcohol (mannitol) instead of an amide-linked amino alcohol, and peptaibols and tetramic acid derivatives have not been isolated previously from the same fungus. The structures of the new compounds were elucidated primarily by high-field NMR (950 and 700 MHz), HRESIMS/MS, and chemical degradations (Marfey’s analysis). All compounds (except 6) were examined for antibacterial and antifungal activities. Compounds 2, 4, and 5 showed antimicrobial activity against S. aureus and several MRSA isolates

Mudanças no perfil funcional de pacientes con patologia psiquiátrica resistente submetidos a neurocirurgia funcional estereotáxica

Con el objetivo de evaluar los resultados de la Neurocirugía Funcional Estereotáctica (NFE) sobre el perfil funcional de los pacientes diagnosticados con Patología Psiquiátrica Resistente (PPR), se realizó un diseño pre/post tratamiento. 13 pacientes fueron evaluados ( = 31 ± 8 años): siete mujeres diagnosticadas con algún Trastorno de la Conducta Alimentaria Resistente (TCAR); tres mujeres diagnosticadas con Trastornos Resistentes Obsesivo Compulsivo y Depresivo (TOC y DR) y tres pacientes (dos mujeres y un hombre) diagnosticados con Depresión Resistente (DR). A estos pacientes se les aplicó la Escala de funcionamiento del paciente Eje K, la cual consta de siete subescalas, y una Escala de Evaluación de la Actividad Global (EAG) antes del tratamiento y después de éste (seis meses posteriores a la NFE). Todos los grupos diagnósticos y el total de los pacientes evaluados presentaron cambios clínicos positivos; sin embargo, sólo el grupo de TCAR mostró importantes cambios clínicos de mejoría en el perfil de funcionamiento, siendo esta diferencia estadísticamente significativa (pre Md = 56; post Md = 84; z= - 2.36, p <0.05). Con la evidencia obtenida se observó que la NFE representa una opción terapéutica emergente efectiva orientada a disminuir el sufrimiento de los pacientes con PPR, así como a mejorar el nivel de funcionamiento global y por ende su calidad de vida. Todos los pacientes del estudio presentaban una condición de resistencia a tratamientos convencionales indicados, la cual había sido documentada por un equipo interdisciplinario experto.Con o objetivo de avaliar os resultados da Neurocirurgía Funcional Estereotáxica (NFE) sobre o perfil funcional dos pacientes diagnosticados com Patologia Psiquiátrica Resistente (PPR), realizou-se um desenho pré/pós tratamento. 13 pacientes foram avaliados ( = 31 ± 8 anos): sete mulheres diagnosticadas com algum Transtorno da Conduta Alimentar Resistente (TCAR); três mulheres diagnosticadas com Transtornos Resistentes Obsessivo Compulsivo e Depressivo (TOC e DR) e três pacientes (duas mulheres e um homem) diagnosticados com Depressão Resistente (DR). A estes pacientes foi aplicada a Escala de funcionamento do paciente Eixo K, a qual consta de sete sub-escalas, e uma Escala de Avaliação da Atividade Global (EAG) antes do tratamento e depois dele (seis meses posteriores à NFE). Todos os grupos diagnósticos e o total dos pacientes avaliados apresentaram mudanças clínicas positivas; porém, só o grupo de TCAR mostrou importantes mudanças clínicas de melhoria no perfil de funcionamento, sendo esta diferença estatisticamente significativa (pré Md= 56; pós Md= 84; z= - 2.36, p <0.05). Com a evidência obtida observou-se que a NFE representa uma opção terapêutica emergente efetiva orientada a diminuir o sofrimento dos pacientes com PPR, bem como a melhorar o nível de funcionamento global e portanto sua qualidade de vida. Todos os pacientes do estudo apresentavam uma condição de resistência a tratamentos convencionais indicados, a qual havia sido documentada por uma equipe interdisciplinar de especialistas.In order to evaluate the results of the Stereotactic Functional Neurosurgery (SFN) on the functional profile of patients diagnosed with Resistant Psychiatric Pathology (RPP), a pre / post treatment design was performed. Thirteen patients were assessed ( = 31 ± 8 years): seven women diagnosed with some type of Resistant Eating Disorder (RED); three women diagnosed with Resistant Obsessive Compulsive Disorder and Resistant Depression (TOC and RD), and three patients (two women and one man) diagnosed with Resistant Depression (RD). The Patient's Functioning Scale, axis K, consisting of seven subscales, and the Assessment of Global Activity Scale (AGAS) were applied before and after treatment (6 months after FSN). All diagnostic groups and all the patients assessed showed positive clinical changes. However, only the RED group showed important clinical improvement in the performance profile with a statistically significant difference (pre Md = 56, Md = 84 post , z = - 2.36, p <0.05). With the evidence obtained it was noted that SFN represents an effective therapeutic option aimed at reducing the suffering of patients with RPP and improve their overall level of functioning and therefore their quality of life. All patients in the study had a condition indicating resistance to conventional treatments which had been documented by an expert multidisciplinary team

Chemoinformatic Expedition of the Chemical Space of Fungal Products

Aim: Fungi are valuable resources for bioactive secondary metabolites. However, the chemical space of fungal secondary metabolites has been studied only on a limited basis. Herein, we report a comprehensive chemoinformatic analysis of a unique set of 207 fungal metabolites isolated and characterized in a USA National Cancer Institute funded drug discovery project. Results: Comparison of the molecular complexity of the 207 fungal metabolites with approved anticancer and nonanticancer drugs, compounds in clinical studies, general screening compounds and molecules Generally Recognized as Safe revealed that fungal metabolites have high degree of complexity. Molecular fingerprints showed that fungal metabolites are as structurally diverse as other natural products and have, in general, drug-like physicochemical properties. Conclusion: Fungal products represent promising candidates to expand the medicinally relevant chemical space. This work is a significant expansion of an analysis reported years ago for a smaller set of compounds (less than half of the ones included in the present work) from filamentous fungi using different structural properties