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1.
J Fish Biol ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599588

RESUMO

Understanding recruitment, the process by which individuals are added to a population or to a fishery, is critical for understanding population dynamics and facilitating sustainable fisheries management. Important variation in recruitment dynamics is observed among populations, wherein some populations exhibit asymptotic productivity and others exhibit overcompensation (i.e., compensatory density-dependence in recruitment). Our ability to understand this interpopulation variability in recruitment patterns is limited by a poor understanding of the underlying mechanisms, such as the complex interactions between density dependence, recruitment, and environment. Furthermore, most studies on recruitment are conducted using an observational design with long time series that are seldom replicated across populations in an experimentally controlled fashion. Without proper replication, extrapolations between populations are tenuous, and the underlying environmental trends are challenging to quantify. To address these issues, we conducted a field experiment manipulating stocking densities of juvenile brook trout Salvelinus fontinalis in three wild populations to show that these neighboring populations-which exhibit divergent patterns of density dependence due to environmental conditions-also have important differences in recruitment dynamics. Testing against four stock-recruitment models (density independent, linear, Beverton-Holt, and Ricker), populations exhibited ~twofold variation in asymptotic productivity, with no overcompensation following a Beverton-Holt model. Although environmental variables (e.g., temperature, pH, depth, substrate) correlated with population differences in recruitment, they did not improve the predictive power in individual populations. Comparing our patterns of recruitment with classic salmonid case studies revealed that despite differences in the shape and parameters of the curves (i.e., Ricker vs. Beverton-Holt), a maximum stocking density of about five YOY fish/m2 emerged. Higher densities resulted in very marginal increases in recruitment (Beverton-Holt) or reduced recruitment due to overcompensation (Ricker).

2.
Mol Ecol ; : e17353, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613250

RESUMO

Effective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimum Ne of 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship between Ne and human activities. Through a quantitative review, we generated a dataset with 4610 georeferenced Ne estimates from 3829 populations, extracted from 723 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal and amphibian populations had a <54% probability of reaching N ̂ e $$ {\hat{N}}_e $$ = 50 and a <9% probability of reaching N ̂ e $$ {\hat{N}}_e $$ = 500. Populations listed as being of conservation concern according to the IUCN Red List had a smaller median N ̂ e $$ {\hat{N}}_e $$ than unlisted populations, and this was consistent across all taxonomic groups. N ̂ e $$ {\hat{N}}_e $$ was reduced in areas with a greater Global Human Footprint, especially for amphibians, birds and mammals, however relationships varied between taxa. We also highlight several considerations for future works, including the role that gene flow and subpopulation structure plays in the estimation of N ̂ e $$ {\hat{N}}_e $$ in wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based on Ne and help prioritise assessment of populations from taxa most at risk of failing to meet conservation thresholds.

3.
Pathology ; 56(3): 313-321, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341306

RESUMO

Histopathology is the gold standard for diagnosing fibrosis, but its routine use is constrained by the need for additional stains, time, personnel and resources. Vibrational spectroscopy is a novel technique that offers an alternative atraumatic approach, with short scan times, while providing metabolic and morphological data. This review evaluates vibrational spectroscopy for the assessment of fibrosis, with a focus on point-of-care capabilities. OVID Medline, Embase and Cochrane databases were systematically searched using PRISMA guidelines for search terms including vibrational spectroscopy, human tissue and fibrosis. Studies were stratified based on imaging modality and tissue type. Outcomes recorded included tissue type, machine learning technique, metrics for accuracy and author conclusions. Systematic review yielded 420 articles, of which 14 were relevant. Ten of these articles considered mid-infrared spectroscopy, three dealt with Raman spectroscopy and one with near-infrared spectroscopy. The metrics for detecting fibrosis were Pearson correlation coefficients ranging from 0.65-0.98; sensitivity from 76-100%; specificity from 90-99%; area under receiver operator curves from 0.83-0.98; and accuracy of 86-99%. Vibrational spectroscopy identified fibrosis in myeloproliferative neoplasms in bone, cirrhotic and hepatocellular carcinoma in liver, end-stage heart failure in cardiac tissue and following laser ablation for acne in skin. It also identified interstitial fibrosis as a predictor of early renal transplant rejection in renal tissue. Vibrational spectroscopic techniques can therefore accurately identify fibrosis in a range of human tissues. Emerging data show that it can be used to quantify, classify and provide data about the nature of fibrosis with a high degree of accuracy with potential scope for point-of-care use.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Análise Espectral Raman/métodos , Pele , Fibrose
4.
Environ Manage ; 73(1): 213-230, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38172273

RESUMO

Habitat degradation is one of the major reasons for freshwater species decline. Hydrogeomorphological processes (such as sediment transport, bank erosion, and flooding) operate at the catchment scale and determine habitat features in river reaches. However, habitat quality indices and restoration for freshwater fish species are often implemented at small spatial scales of a few hundred metres. The Morphological Quality Index (MQI) considers fluvial processes at larger scales as well as channel forms, human impacts, and historical changes, but few studies have assessed its relevance for ecosystem health. We investigated relationships between the MQI, habitat quality (using the Qualitative Habitat Evaluation Index, QHEI), land cover, and fish metrics (number of fish species, index of biotic integrity (IBI), and trout biomass) in 26 salmonid streams in Aotearoa New Zealand and Southern Ontario, Canada. We found a significant correlation between the MQI and QHEI, and both metrics were correlated with urban and native forest proportion in the catchment. However, we found no relation between the MQI and the proportion of agricultural land in the catchment, while the QHEI was correlated with agricultural land in the riparian zone, highlighting the importance of vegetated riparian buffers in providing fish habitat. Establishing a strong correlation with fish metrics remains challenging. Nevertheless, a modified MQI targeting ecological health could be used as an effective management tool for aquatic conservation.


Assuntos
Ecossistema , Salmonidae , Animais , Peixes , Nova Zelândia , Ontário , Rios
5.
Bioengineering (Basel) ; 10(12)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38135987

RESUMO

The rapid rise of artificial intelligence (AI) in medicine in the last few years highlights the importance of developing bigger and better systems for data and model sharing. However, the presence of Protected Health Information (PHI) in medical data poses a challenge when it comes to sharing. One potential solution to mitigate the risk of PHI breaches is to exclusively share pre-trained models developed using private datasets. Despite the availability of these pre-trained networks, there remains a need for an adaptable environment to test and fine-tune specific models tailored for clinical tasks. This environment should be open for peer testing, feedback, and continuous model refinement, allowing dynamic model updates that are especially important in the medical field, where diseases and scanning techniques evolve rapidly. In this context, the Discovery Viewer (DV) platform was developed in-house at the Biomedical Engineering and Imaging Institute at Mount Sinai (BMEII) to facilitate the creation and distribution of cutting-edge medical AI models that remain accessible after their development. The all-in-one platform offers a unique environment for non-AI experts to learn, develop, and share their own deep learning (DL) concepts. This paper presents various use cases of the platform, with its primary goal being to demonstrate how DV holds the potential to empower individuals without expertise in AI to create high-performing DL models. We tasked three non-AI experts to develop different musculoskeletal AI projects that encompassed segmentation, regression, and classification tasks. In each project, 80% of the samples were provided with a subset of these samples annotated to aid the volunteers in understanding the expected annotation task. Subsequently, they were responsible for annotating the remaining samples and training their models through the platform's "Training Module". The resulting models were then tested on the separate 20% hold-off dataset to assess their performance. The classification model achieved an accuracy of 0.94, a sensitivity of 0.92, and a specificity of 1. The regression model yielded a mean absolute error of 14.27 pixels. And the segmentation model attained a Dice Score of 0.93, with a sensitivity of 0.9 and a specificity of 0.99. This initiative seeks to broaden the community of medical AI model developers and democratize the access of this technology to all stakeholders. The ultimate goal is to facilitate the transition of medical AI models from research to clinical settings.

6.
Nature ; 623(7985): 157-166, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37853118

RESUMO

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).


Assuntos
Neoplasias Encefálicas , Glioblastoma , Herpesvirus Humano 1 , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioblastoma/imunologia , Glioblastoma/patologia , Nestina/genética , Terapia Viral Oncolítica/efeitos adversos , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Vírus Oncolíticos/fisiologia , Reprodutibilidade dos Testes , Análise de Sobrevida , Linfócitos T/citologia , Linfócitos T/imunologia , Resultado do Tratamento , Microambiente Tumoral/imunologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/fisiologia
7.
Opt Express ; 31(16): 26610-26625, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710518

RESUMO

This paper outlines an experimental demonstration of a Bayesian image reconstruction approach to achieve rapid single-photon color imaging of moving objects. The capacity to extract the color of objects is important in a variety of target identification and computer vision applications. Nonetheless, it remains challenging to achieve high-speed color imaging of moving objects in low-photon flux environments. The low-photon regime presents particular challenges for efficient spectral separation and identification, while unsupervised image reconstruction algorithms are often slow and computationally expensive. In this paper, we address both of these difficulties using a combination of hardware and computational solutions. We demonstrate color imaging using a Single-Photon Avalanche Diode (SPAD) detector array for rapid, low-light-level data acquisition, with an integrated color filter array (CFA) for efficient spectral unmixing. High-speed image reconstruction is achieved using a bespoke Bayesian algorithm to produce high-fidelity color videos. The analysis is conducted first on simulated data allowing different pixel formats and photon flux scenarios to be investigated. Experiments are then performed using a plasmonic metasurface-based CFA, integrated with a 64 × 64 pixel format SPAD array. Passive imaging is conducted using white-light illumination of multi-colored, moving targets. Intensity information is recorded in a series of 2D photon-counting SPAD frames, from which accurate color information is extracted using the fast Bayesian method introduced herein. The per-frame reconstruction rate proves to be hundreds of times faster than the previous computational method. Furthermore, this approach yields additional information in the form of uncertainty measures, which can be used to assist with imaging system optimization and decision-making in real-world applications. The techniques demonstrated point the way towards rapid video-rate single-photon color imaging. The developed Bayesian algorithm, along with more advanced SPAD technology and utilization of time-correlated single-photon counting (TCSPC) will permit live 3D, color videography in extremely low-photon flux environments.

8.
Prog Orthod ; 24(1): 23, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37423974

RESUMO

OBJECTIVE: The objective of this study was to measure the forces and moments exerted by direct printed aligners (DPAs) with varying facial and lingual aligner surface thicknesses, in all three planes of space, during lingual movement of a maxillary central incisor. MATERIALS AND METHODS: An in vitro experimental setup was used to quantify forces and moments experienced by a programmed tooth to be moved and by adjacent anchor teeth, during lingual movement of a maxillary central incisor. DPAs were directly 3D-printed with Tera Harz TC-85 (Graphy Inc., Seoul, South Korea) clear photocurable resin in 100-µm layers. Three multi-axis sensors were used to measure the moments and forces generated by 0.50 mm thick DPAs modified with labial and lingual surface thicknesses of 1.00 mm in selective locations. The sensors were connected to three maxillary incisors (the upper left central, the upper right central, and the upper left lateral incisors) during 0.50 mm of programmed lingual bodily movement of the upper left central incisor. Moment-to-force ratios were calculated for all three incisors. Aligners were benchtop tested in a temperature-controlled chamber at intra-oral temperature to simulate intra-oral conditions. RESULTS: The results showed that increased facial thickness of DPAs slightly reduced force levels on the upper left central incisor compared to DPAs of uniform thickness of 0.50 mm. Additionally, increasing the lingual thickness of adjacent teeth reduced force and moment side effects on the adjacent teeth. DPAs can produce moment-to-force ratios indicative of controlled tipping. CONCLUSIONS: Targeted increases in thickness of direct 3D-printed aligners change the magnitude of forces and moments generated, albeit in complex patterns that are difficult to predict. The ability to vary labiolingual thicknesses of DPAs is promising to optimize the prescribed orthodontic movements while minimizing unwanted tooth movements, thereby increasing the predictability of tooth movements.


Assuntos
Incisivo , Aparelhos Ortodônticos Removíveis , Humanos , Desenho de Aparelho Ortodôntico , Técnicas de Movimentação Dentária/métodos , Face
9.
Eur J Neurol ; 30(9): 2752-2760, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37306550

RESUMO

BACKGROUND AND PURPOSE: Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. METHODS: In the Ausimmune case-control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein-Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. RESULTS: In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08-4.46, p = 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS risk-related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). CONCLUSIONS: HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 6 , Esclerose Múltipla , Humanos , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , Estudos de Casos e Controles , Herpesvirus Humano 6/genética , Herpesvirus Humano 3/genética , Imunoglobulina G , Sistema Nervoso Central
10.
Int J Clin Pract ; 2023: 9593796, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333947

RESUMO

Method: In a comparative experimental cross-sectional study, RNA was extracted from oral swabs and blood samples from 25 healthy individuals at the Department of Molecular Medicine, KNUST. RNA was extracted by the manual AGPC extraction method and commercial RNA extraction kits. The quantity (ng/µl) and purities (260/280 nm) of the extracted RNA were measured spectrophotometrically using the IMPLEN NanoPhotometer® N60. The presence of RNA in the extracts was confirmed using 2% agarose gel electrophoresis. Statistical analyses were conducted using R language. Results: The yield of RNA extracted from blood and oral swab samples using modified AGPC was significantly higher compared to the commercial methods (p < 0.0001). However, the purity of RNA extracted by the manual AGPC method from blood was significantly lower than the commercial methods (p < 0.0001). Moreover, the purity from oral swabs using the manual AGPC method was significantly lower compared to QIAamp (p < 0.0001) and the OxGEn kits method (p < 0.001). Conclusion: The modified manual AGPC method has a very high yield of RNA extracts using blood samples, which could serve as an alternate cost-effective method for RNA extraction in resource-limited laboratories; however, its purity may not be suitable for downstream processes. Moreover, the manual AGPC method may not be suitable for extracting RNA from oral swab samples. Future investigation is needed to improve the purity of the manual AGPC RNA extraction method and also confirmation of the obtained results by PCR amplification and RNA purity verification by sequencing.


Assuntos
Clorofórmio , Fenol , Humanos , Estudos Transversais , Laboratórios , Fenóis , RNA
11.
Phys Chem Chem Phys ; 25(27): 18011-18022, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37377444

RESUMO

The MgO-CO2-H2O system have a variety of important industrial applications including in catalysis, immobilisation of radionuclides and heavy metals, construction, and mineralisation and permanent storage of anthropogenic CO2. Here, we develop a computational approach to generate phase stability plots for the MgO-CO2-H2O system that do not rely on traditional experimental corrections for the solid phases. We compare the predictions made by several dispersion-corrected density-functional theory schemes, and we include the temperature-dependent Gibbs free energy through the quasi-harmonic approximation. We locate the Artinite phase (Mg2CO3(OH)2·3H2O) within the MgO-CO2-H2O phase stability plot, and we demonstrate that this widely-overlooked hydrated and carbonated phase is metastable and can be stabilised by inhibiting the formation of fully-carbonated stable phases. Similar considerations may apply more broadly to other lesser known phases. These findings provide new insight to explain conflicting results from experimental studies, and demonstrate how this phase can potentially be stabilised by optimising the synthesis conditions.

13.
Ann Biomed Eng ; 51(9): 2070-2085, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37227601

RESUMO

Commotio cordis is one of the leading causes of sudden cardiac death in youth baseball. Currently, there are chest protector regulations regarding the prevention of Commotio cordis in baseball and lacrosse; however, they are not fully optimized. For the advancement of Commotio cordis safety, it is vital to include various age groups and a variety of impact angles in the testing process. This study employed finite element models and simulated Commotio cordis-inducing baseball collisions for different velocities, impact angles, and age groups. Commotio cordis risk response was characterized in terms of left ventricular strain and pressure, chest band and rib deformation, and force from impact. Normalized rib and chest band deformation when correlated with left ventricular strain resulted in R2 = 0.72, and R2 = 0.76, while left ventricular pressure resulted in R2 = 0.77, R2 = 0.68 across all velocities and impact angles in the child models. By contrast, the resultant reaction force risk metric as used by the National Operating Committee on Standards for Athletic Equipment (NOCSAE) demonstrated a correlation of R2 = 0.20 in the child models to ventricular strain, while illustrating a correlation to pressure of R2 = 0.74. When exploring future revisions to Commotio cordis safety requirements, the inclusion of deformation-related risk metrics at the level of the left ventricle should be considered.


Assuntos
Commotio Cordis , Ferimentos não Penetrantes , Criança , Adolescente , Humanos , Commotio Cordis/prevenção & controle , Commotio Cordis/complicações , Fibrilação Ventricular , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Equipamentos de Proteção , Equipamentos Esportivos
14.
Evol Appl ; 15(11): 1792-1805, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36426123

RESUMO

Sustainable management of exploited populations benefits from integrating demographic and genetic considerations into assessments, as both play a role in determining harvest yields and population persistence. This is especially important in populations subject to size-selective harvest, because size selective harvesting has the potential to result in significant demographic, life-history, and genetic changes. We investigated harvest-induced changes in the effective number of breeders ( N ^ b ) for introduced brook trout populations (Salvelinus fontinalis) in alpine lakes from western Canada. Three populations were subject to 3 years of size-selective harvesting, while three control populations experienced no harvest. The N ^ c decreased consistently across all harvested populations (on average 60.8%) but fluctuated in control populations. There were no consistent changes in N ^ b between control or harvest populations, but one harvest population experienced a decrease in N ^ b of 63.2%. The N ^ b / N ^ c ratio increased consistently across harvest lakes; however we found no evidence of genetic compensation (where variance in reproductive success decreases at lower abundance) based on changes in family evenness ( FE ^ ) and the number of full-sibling families ( N ^ fam ). We found no relationship between FE ^ and N ^ c or between N ^ fam / N ^ c and FE ^ . We posit that change in N ^ b was buffered by constraints on breeding habitat prior to harvest, such that the same number of breeding sites were occupied before and after harvest. These results suggest that effective size in harvested populations may be resilient to considerable changes in Nc in the short-term, but it is still important to monitor exploited populations to assess the risk of inbreeding and ensure their long-term survival.

15.
ACS Photonics ; 9(10): 3245-3252, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36281330

RESUMO

The polarization state of light is a key parameter in many imaging systems. For example, it can image mechanical stress and other physical properties that are not seen with conventional imaging and can also play a central role in quantum sensing. However, polarization is more difficult to image, and polarimetry typically involves several independent measurements with moving parts in the measurement device. Metasurfaces with interleaved designs have demonstrated sensitivity to either linear or circular/elliptical polarization states. Here, we present an all-dielectric meta-polarimeter for direct measurement of any arbitrary polarization state from a single-unit-cell design. By engineering a completely asymmetric design, we obtained a metasurface that can excite eigenmodes of the nanoresonators, thus displaying a unique diffraction pattern for not only any linear polarization state but all elliptical polarization states (and handedness) as well. The unique diffraction patterns are quantified into Stokes parameters with a resolution of 5° and with a polarization state fidelity of up to 99 ± 1%. This holds promise for applications in polarization imaging and quantum state tomography.

16.
BMC Med Inform Decis Mak ; 22(1): 5, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991567

RESUMO

BACKGROUND: The objective of this work to calculate prescribed quantity of an active pharmaceutical ingredient (API) in prescription medications for human use, to facilitate research on the prediction of amount of API released to the environment and create an open-data tool to facilitate spatiotemporal and long-term prescription trends for wider usage. DESIGN: We have developed an R package, PrAna to calculate the prescribed quantity (in kg) of an APIs by postcode using England's national level prescription data provided by National Health Service, for the years 2015-2018. Datasets generated using PrAna can be visualized in a real-time interactive web-based tool, PrAnaViz to explore spatiotemporal and long-term trends. The visualisations can be customised by selecting month, year, API, and region. RESULTS: PrAnaViz's targeted API approach is demonstrated with the visualisation of prescribed quantities of 14 APIs in the Bath and North East Somerset (BANES) region during 2018. Once the APIs list is loaded, the back end retrieves relevant data and populates the graphs based on user-defined data features in real-time. These plots include the prescribed quantity of APIs over a year, by month, and individual API by month, general practice, postcode, and medicinal form. The non-targeted API approach is demonstrated with the visualisation of clarithromycin prescribed quantities at different postcodes in the BANES region. CONCLUSION: PrAna and PrAnaViz enables the analysis of spatio-temporal and long-term trends with prescribed quantities of different APIs by postcode. This can be used as a support tool for policymakers, academics and researchers in public healthcare, and environmental scientist to monitor different group of pharmaceuticals emitted to the environment and for prospective risk assessment of pharmaceuticals in the environment.


Assuntos
Atenção à Saúde , Medicina Estatal , Inglaterra , Humanos , Atenção Primária à Saúde , Estudos Prospectivos
17.
Neuro Oncol ; 24(6): 951-963, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850166

RESUMO

BACKGROUND: Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signaling, providing the rationale for a combination trial with immune checkpoint inhibition. METHODS: An open-label, multi-institutional, dose-escalation phase I trial in rGBM subjects (NCT03636477) accrued 21 subjects in 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg) and VDX (10 mg) (n = 3); (2) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (10 mg) (n = 3); and (3) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (20 mg) (n = 15). Nivolumab was administered 7 (±3) days before resection of the rGBM followed by peritumoral injection of IL-12 gene therapy. VDX was administered 3 hours before and then for 14 days after surgery. Nivolumab was administered every two weeks after surgery. RESULTS: Toxicities of the combination were comparable to IL-12 gene monotherapy and were predictable, dose-related, and reversible upon withholding doses of VDX and/or nivolumab. VDX plasma pharmacokinetics demonstrate a dose-response relationship with effective brain tumor tissue VDX penetration and production of IL-12. IL-12 levels in serum peaked in all subjects at about Day 3 after surgery. Tumor IFNγ increased in post-treatment biopsies. Median overall survival (mOS) for VDX 10 mg with nivolumab was 16.9 months and for all subjects was 9.8 months. CONCLUSION: The safety of this combination immunotherapy was established and has led to an ongoing phase II clinical trial of immune checkpoint blockade with controlled IL-12 gene therapy (NCT04006119).


Assuntos
Antineoplásicos Imunológicos , Glioblastoma , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Terapia Genética , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Interleucina-12/genética , Nivolumabe/uso terapêutico
18.
Nurs Rep ; 11(3): 728-740, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34968346

RESUMO

BACKGROUND: Patient-centered outcomes research seeks to answer patient-centered questions. The process includes varied locations and individuals throughout the care continuum to address individual differences and constraints in implementation and dissemination. PROBLEM: This paper intends to answer this question: do academic nurses practice what they preach by assisting patient-centered outcomes research and researchers through their engagement with patients, caregivers, and other community stakeholder partners in nursing research? APPROACH: This paper provides an overview of how academic nurses in a single institution (the University of Texas Medical Branch at Galveston School of Nursing) began to embrace patient-centered outcomes research. CONCLUSION: Whether academic nurses are practicing what they preach in terms of patient-centered outcomes research remains uncertain. More examples from academia are required to make that determination. Academic nurses worldwide have embarked on a steep learning curve to embrace patient-centered outcomes research. This journey will require patience and a systematic strategy.

19.
20.
Microsyst Nanoeng ; 7: 21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567735

RESUMO

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using l-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing.

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