Search Results (18)

Prostate cancer is a common cancer among males in the US, but little is known about its risk factors, including trace elements. The primary aim of this study was to examine prostate cancer and its association with arsenic and selenium in toenails. We conducted a small, nested case-control study of men residing in Iowa within the Agricultural Health Study cohort, where we also collected toenail samples to test for arsenic and other trace elements. Toenail samples were sent for neutron activation analysis aimed at long-lived trace elements, including arsenic. Logistic regression was used to estimate odds ratios (ORs) for trace element exposures and prostate cancer. A total of 66 prostate cancer cases and 173 healthy controls returned questionnaires, over 99% of which included toenail samples. An increased risk was seen for the highest levels of arsenic (OR = 3.4 confidence interval (CI) of 1.3–8.6 and OR = 2.2, 95% CI of 0.9–5.6) and the highest level of selenium (2.0, 95% CI of 1.0–4.0). These data also show detectable levels of over 50% for 14 of 22 elements detected in the toenails. The association seen here with arsenic and prostate cancer further supports ecological studies finding an association with community levels of arsenic and prostate cancer incidence and mortality. Full article

Idecabtagene vicleucel (ide-cel) was the first FDA-approved chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma (RRMM) patients. This was the first study to evaluate patient-reported outcomes (PROs) among RRMM patients receiving ide-cel in standard of care (SOC). We prospectively assessed health-related quality of life (HRQOL) and symptoms from pre-infusion (baseline) through day (D)90 post-infusion. Baseline PRO associations with patient characteristics, mean PRO changes, and time to stable change were evaluated with t-tests, linear mixed-effects models, and Kaplan–Meier analyses, respectively. Within-person change scores and minimally important difference thresholds determined clinical and meaningful significance. Participants (n = 42) were a median of 66 years old (range: 43–81). At baseline, extramedullary disease was associated with worse physical well-being (p = 0.008), global pain (p < 0.001), performance status (p = 0.002), and overall symptom burden (p < 0.001). Fatigue (p < 0.001) and functional well-being (p = 0.003) worsened by D7 before returning to baseline levels. Overall HRQOL (p = 0.008) and physical well-being (p < 0.001) improved by D60. Most participants reported PRO improvement (10–57%) or maintenance (23–69%) by D90. The median time it took to stabile deterioration in functional well-being was 14 days. The median time it took to stabile improvement in physical and emotional well-being was 60 days. Overall, RRMM patients reported improvements or maintenance of HRQOL and symptom burden after SOC ide-cel. Full article

Metabolomics analysis of urine before and after overactive bladder (OAB) treatment may demonstrate a unique molecular profile, allowing predictions of responses to treatment. This feasibility study aimed to correlate changes in urinary metabolome with changes in OAB symptoms after intravesical onabotulinumtoxinA (BTX-A) injections for refractory OAB. Women 18 years or older with non-neurogenic refractory OAB were recruited to complete OAB-V8 questionnaires and submit urine samples before and after 100 units intravesical BTX-A injection. Samples were submitted to CE-TOFMS metabolomics profiling. Data were expressed as percent of change from pre-treatment and were correlated with OAB-V8 score improvement. Urinary metabolite changes in the OAB-V8 groups were compared using the Kruskal–Wallis test, and associations between metabolites and OAB-V8 scores were examined using quantile regression analysis. Of 61 urinary metabolites commonly detected before and after BTX-A, there was a statistically significant decrease in adenosine and an increase in N8-acetylspermidine and guanidinoacetic acid levels associated with OAB score improvement, suggesting that intravesical BTX-A injection modifies the urinary metabolome. These urinary metabolites could provide insight into OAB pathophysiology and help identify patients who would benefit most from chemodenervation. Full article

A set of thermally rearranged mixed matrix membranes (TR-MMMs) was manufactured and tested for gas separation. These membranes were obtained through the thermal treatment of a precursor MMM with a microporous polymer network and an o-hydroxypolyamide,(HPA) created through a reaction of 2,2-bis(3-amino-4-hydroxyphenyl)-hexafluoropropane (APAF) and 5′-terbutil-m-terfenilo-3,3″-dicarboxylic acid dichloride (tBTmCl). This HPA was blended with different percentages of a porous polymer network (PPN) filler, which produced gas separation MMMs with enhanced gas permeability but with decreased selectivity. The thermal treatment of these MMMs gave membranes with excellent gas separation properties that did not show the selectivity decreasing trend. It was observed that the use of the PPN load brought about a small decrease in the initial mass losses, which were lower for increasing PPN loads. Regarding the glass transition temperature, it was observed that the use of the filler translated to a slightly lower Tg value. When these MMMs and TR-MMMs were compared with the analogous materials created from the isomeric 5′-terbutil-m-terfenilo-4,4″-dicarboxylic acid dichloride (tBTpCl), the permeability was lower for that of tBTmCl, compared with the one from tBTpCl, although selectivity was quite similar. This fact could be attributed to a lower rigidity as roughly confirmed by the segmental length of the polymer chain as studied by WAXS. A model for FFV calculation was proposed and its predictions compared with those evaluated from density measurements assuming a matrix-filler interaction or ideal independence. It turns out that permeability as a function of FFV for TR-MMMs follows an interaction trend, while those not thermally treated follow the non-interaction trend until relatively high PPN loads were reached. Full article

Training deep learning models requires having the right data for the problem and understanding both your data and the models’ performance on that data. Training deep learning models is difficult when data are limited, so in this paper, we seek to answer the following question: how can we train a deep learning model to increase its performance on a targeted area with limited data? We do this by applying rotation data augmentations to a simulated synthetic aperture radar (SAR) image dataset. We use the Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction technique to understand the effects of augmentations on the data in latent space. Using this latent space representation, we can understand the data and choose specific training samples aimed at boosting model performance in targeted under-performing regions without the need to increase training set sizes. Results show that using latent space to choose training data significantly improves model performance in some cases; however, there are other cases where no improvements are made. We show that linking patterns in latent space is a possible predictor of model performance, but results require some experimentation and domain knowledge to determine the best options. Full article

Mixed-matrix membranes (MMMs) consisting of an ortho-hydroxy polyamide (HPA) matrix, and variable loads of a porous polymer network (PPN) were thermally treated to induce the transformation of HPA to polybenzoxazole (β-TR-PBO). Two different HPAs were synthesized to be used as a matrix, 6FCl-APAF and tBTpCl-APAF, while the PPN used as a filler was prepared by reacting triptycene and trifluoroacetophenone. The permeability of He, H₂, N₂, O₂, CH₄ and CO₂ gases through these MMMs are analyzed as a function of the fraction of free volume (FFV) of the membrane and the kinetic diameter of the gas, allowing for the evaluation of the free volume. Thermal rearrangement entails an increase in the FFV. Both before and after thermal rearrangement, the free volume increases with the PPN content very similarly for both polymeric matrices. It is shown that there is a portion of free volume that is inaccessible to permeation (occluded volume), probably due to it being trapped within the filler. In fact, permeability and selectivity change below what could be expected according to densities, when the fraction of occluded volume increases. A higher filler load increases the percentage of inaccessible or trapped free volume, probably due to the increasing agglomeration of the filler. On the other hand, the phenomenon is slightly affected by thermal rearrangement. The fraction of trapped free volume seems to be lower for membranes in which the tBTpCl-APAF is used as a matrix than for those with a 6FCl-APAF matrix, possibly because tBTpCl-APAF could approach the PPN better. The application of an effective medium theory for permeability allowed us to extrapolate for a 100% filler, giving the same value for both thermally rearranged and non-rearranged MMMs. The pure filler could also be extrapolated by assuming the same tendency as in the Robeson’s plots for MMMs with low filler content. Full article

Mixed matrix membranes (MMMs) consisting of a blend of a hydroxypolyamide (HPA) matrix and variable loads of a porous polymer network (PPN) were thermally treated to induce the transformation of HPA to polybenzoxazole (β-TR-PBO). Here, the HPA matrix was a hydroxypolyamide having two hexafluoropropyilidene moieties, 6FCl-APAF, while the PPN was prepared by reacting triptycene (TRP) and trifluoroacetophenone (TFAP) in a superacid solution. The most probable size of the PPN particles was 75 nm with quite large distributions. The resulting membranes were analyzed by SEM and AFM. Up to 30% PPN loads, both SEM and AFM images confirmed quite planar surfaces, at low scale, with limited roughness. Membranes with high hydrogen permeability and good selectivity for the gas pairs H₂/CH₄ and H₂/N₂ were obtained. For H₂/CO₂, selectivity almost vanished after thermal rearrangement. In all cases, their hydrogen permeability increased with increasing loads of PPN until around 30% PPN with ulterior fairly abrupt decreasing of permeability for all gases studied. Thermal rearrangement of the MMMs resulted in higher permeabilities but lower selectivities. For all the membranes and gas pairs studied, the balance of permeability vs. selectivity surpassed the 1991 Robeson’s upper bound, and approached or even exceeded the 2008 line, for MMMs having 30% PPN loads. In all cases, the HPA-MMMs before thermal rearrangement provided good selectivity versus permeability compromise, similar to their thermally rearranged counterparts but in the zone of high selectivity. For H₂/CH₄, H₂/N₂, these nonthermally rearranged MMMs approach the 2008 Robeson’s upper bound while H₂/CO₂ gives selective transport favoring H₂ on the 1991 Robeson’s bound. Thus, attending to the energy cost of thermal rearrangement, it could be avoided in some cases especially when high selectivity is the target rather than high permeability. Full article

Increasing numbers of people in England experience homelessness, substance use, and repeated offending (known as ‘severe and multiple disadvantage’; SMD). Populations experiencing SMD often have extremely poor oral health, which is closely inter-linked with high levels of substance use, smoking, and poor diet. This study aims to undertake an evidence synthesis to identify the effectiveness, resource requirements, and factors influencing the implementation and acceptability of oral health and related health behaviour interventions in adults experiencing SMD. Two systematic reviews will be conducted using mixed-methods. Review 1 will investigate the effectiveness and resource implications of oral health and related health behaviours (substance use, smoking, diet) interventions; Review 2 will investigate factors influencing the implementation of such interventions. The population includes adults (≥18 years) experiencing SMD. Standard review methods in terms of searches, screening, data extraction, and quality appraisal will be conducted. Narrative syntheses will be conducted. If feasible, a meta-analysis will be conducted for Review 1 and a thematic synthesis for Review 2. Evidence from the two reviews will then be synthesised together. Input from people with experience of SMD will be sought throughout to inform the reviews. An initial logic model will be iteratively refined during the review. Full article

The wide scale adoption of Artificial Intelligence (AI) will require that AI engineers and developers can provide assurances to the user base that an algorithm will perform as intended and without failure. Assurance is the safety valve for reliable, dependable, explainable, and fair intelligent systems. AI assurance provides the necessary tools to enable AI adoption into applications, software, hardware, and complex systems. AI assurance involves quantifying capabilities and associating risks across deployments including: data quality to include inherent biases, algorithm performance, statistical errors, and algorithm trustworthiness and security. Data, algorithmic, and context/domain-specific factors may change over time and impact the ability of AI systems in delivering accurate outcomes. In this paper, we discuss the importance and different angles of AI assurance, and present a general framework that addresses its challenges. Full article

Background: Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. In this study, we investigated rare germline genetic variants in genes involved in TBXT/chordoma-related signaling pathways and other biological processes in chordoma patients from North America and China. Methods: We identified variants that were very rare in general population and internal control datasets and showed evidence for pathogenicity in 265 genes in a whole exome sequencing (WES) dataset of 138 chordoma patients of European ancestry and in a whole genome sequencing (WGS) dataset of 80 Chinese patients with skull base chordoma. Results: Rare and likely pathogenic variants were identified in 32 of 138 European ancestry patients (23%), including genes that are part of notochord development, PI3K/AKT/mTOR, Sonic Hedgehog, SWI/SNF complex and mesoderm development pathways. Rare pathogenic variants in COL2A1, EXT1, PDK1, LRP2, TBXT and TSC2, among others, were also observed in Chinese patients. Conclusion: We identified several rare loss-of-function and predicted deleterious missense variants in germline DNA from patients with chordoma, which may influence chordoma predisposition and reflect a complex susceptibility, warranting further investigation in large studies. Full article

A hydroxypolyamide (HPA) manufactured from 2,2-bis(3-amino-4-hydroxy phenyl)-hexafluoropropane (APAF) diamine and 5′-terbutyl-m-terphenyl-4,4′′-dicarboxylic acid chloride (tBTpCl), and a copolyimide produced by stochiometric copolymerization of APAF and 4,4′-(hexafluoroisopropylidene) diamine (6FpDA), using the same diacid chloride, were obtained and used as polymeric matrixes in mixed matrix membranes (MMMs) loaded with 20% (w/w) of two porous polymer networks (triptycene-isatin, PPN-1, and triptycene-trifluoroacetophenone, PPN-2). These MMMs, and also the thermally rearranged membranes (TR-MMMs) that underwent a thermal treatment process to convert the o-hydroxypolyamide moieties to polybenzoxazole ones, were characterized, and their gas separation properties evaluated for H₂, N₂, O₂, CH₄, and CO₂. Both TR process and the addition of PPN increased permeability with minor decreases in selectivity for all gases tested. Excellent results were obtained, in terms of the permeability versus selectivity compromise, for H₂/CH₄ and H₂/N₂ separations with membranes approaching the 2008 Robeson’s trade-off line. The best gas separation properties were obtained when PPN-2 was used. Finally, gas permeation was characterized in terms of chain intersegmental distance and fraction of free volume of the membrane along with the kinetic diameters of the permeated gases. The intersegmental distance increased after TR and/or the addition of PPN-2. Permeability followed an exponential dependence with free volume and a quadratic function of the kinetic diameter of the gas. Full article

Geocoding is a powerful tool for environmental exposure assessments that rely on spatial databases. Geocoding processes, locators, and reference datasets have improved over time; however, improvements have not been well-characterized. Enrollment addresses for the Agricultural Health Study, a cohort of pesticide applicators and their spouses in Iowa (IA) and North Carolina (NC), were geocoded in 2012–2016 and then again in 2019. We calculated distances between geocodes in the two periods. For a subset, we computed positional errors using “gold standard” rooftop coordinates (IA; N = 3566) or Global Positioning Systems (GPS) (IA and NC; N = 1258) and compared errors between periods. We used linear regression to model the change in positional error between time periods (improvement) by rural status and population density, and we used spatial relative risk functions to identify areas with significant improvement. Median improvement between time periods in IA was 41 m (interquartile range, IQR: −2 to 168) and 9 m (IQR: −80 to 133) based on rooftop coordinates and GPS, respectively. Median improvement in NC was 42 m (IQR: −1 to 109 m) based on GPS. Positional error was greater in rural and low-density areas compared to in towns and more densely populated areas. Areas of significant improvement in accuracy were identified and mapped across both states. Our findings underscore the importance of evaluating determinants and spatial distributions of errors in geocodes used in environmental epidemiology studies. Full article

Young homeless people make up nearly one-third of those experiencing homelessness. The need to provide an educative approach, to strengthen social interacting, and construct new knowledge to increase social inclusivity, is required. The aim of this qualitative exploration was to use critical consciousness as an educative tool, to co-design, implement, and evaluate a series of oral health and health pedagogical workshops to strengthen social engagement and to construct new health knowledge, with, and for, homeless young people and their service providers. An action research design permitted the simultaneous development, implementation, and evaluation of the pedagogical workshop program. A Non-Governmental Organization (NGO), providing supported accommodation for young homeless people, acted as the partner organization. Thirteen young people and five staff members from this NGO participated and co-designed eight workshops. Qualitative data collection included unstructured post-intervention interviews together with verbatim quotes from the group discussions during the workshops and from the post-workshop questionnaires. The qualitative analysis was informed by content analysis to permit the emergence of key themes from the data. The two themes were: 1. ‘trust building and collective engaging’ and 2. ‘constructing knowledge and developing skills’. Theme 1 highlighted engagement with the service provider, illustrating the transformation of the young people’s relationships, strengthening of their social interacting, and enabling their critical reflexive thinking on sensitive issues present in the homelessness trajectory. Theme 2 illustrated the young people’s ability to share, lend, and encode their new health information and convert it into an understandable and useable form. This new comprehension permitted their behavior change and social interaction. These findings provide an approach to increase young people’s knowledge, health literacy, and strengthen their social interacting to support community action. Full article

Smile4life is an intervention aimed at improving the oral health of people experiencing homelessness in Scotland. The purpose of this research was to determine how this intervention was being translated from guidance into action. Data concerning Smile4life working practices were collected in three NHS Boards using participant observation. Fieldnotes taken during these observations were analysed using content analysis. This analysis revealed that there were working alliances between the oral health practitioner, the Third Sector staff, and the homeless service users, and that these alliances were affected by various barriers and enablers. The observation sessions also highlighted variations in working practices. Full article

The aim of this research was to conduct an oral health and psychosocial needs assessment of a homeless population in Scotland to determine the levels of unmet need and provide recommendations for oral health improvement. A non-probability convenience sample of homeless people residing in seven Scottish Health Boards was collected. All consenting participants were asked to complete a questionnaire assessing their health and psychosocial needs, dental anxiety, and oral health-related quality of life. The participants’ oral health was examined by a trained and calibrated dentist and dental nurse. Eight hundred and fifty-three homeless people consented to take part. Participants had a mean D_3cvMFT score of 16.9 (95% CI: 16.3, 17.6). Dental anxiety was high, with 20% scoring as dentally phobic. Respondents with higher dental anxiety were found to have significantly greater mean numbers of filled teeth than those with lower dental anxiety (t = −2.9, p < 0.05). Common oral health impacts were painful aching and discomfort while eating, experienced occasionally by 31% and 27% of the respondents, respectively. Fifty-eight percent of participants were found to have a depressive illness, and obvious decay experience was significantly higher among this section of participants (t = −4.3, p < 0.05). Homeless people in Scotland were found to be in need of a more accessible dental service than is currently available. An enhanced service should meet the oral health and psychosocial needs of this population to improve their oral health and quality of life. Full article