Search Results (7)

The complex pathway for new drug reimbursement in Canada has been well documented. Drugs with promising early efficacy data may receive a Notice of Compliance with Conditions (NOC/c) from Health Canada. For oncology drugs that receive NOC/c, the pathway through positive review by Canada’s Drug Agency (CDA-AMC) and subsequent public reimbursement can take over 500 days. To address this challenge, in September 2023, CDA-AMC announced a new Time-Limited Recommendation (TLR) category, and in parallel, the pan-Canadian Pharmaceutical Alliance (pCPA) developed a set of principles and conditions for a Temporary Access Process (pTAP). This accelerated access pathway, the first of its kind in Canada, enables patients with advanced diseases to gain timely access to promising therapies while managing the uncertainties and risks associated with early approvals. This report provides a first assessment of the impact of the TLR-pTAP process on the reimbursement timelines for oncology drugs approved with NOC/c. Methods: The time from NOC/c approvals for oncology drugs between 1 January 2023 to 31 December 2024, to first provincial listings, and the timelines of the Health Canada, CDA-AMC, and pCPA review processes, were collected and evaluated. Results: Nine oncology NOC/c were granted during the selected period, of which three products, Columvi, Akeega, and Epkinly, received provincial listings, and the median time from regulatory approvals to provincial listings is 509 days (IQ range 306–544 days). One drug, Epkinly, has elected to adopt the TLR-pTAP pathway. Compared to the conventional reimbursement pathway—including for the drug Columvi, whose therapeutic profile is similar to that of Epkinly—the new pathway reduced the time to first provincial listing by over 200 days. A stepwise analysis indicates that the most significant accelerator within the TLR-pTAP pathway is the pCPA’s prioritization and processing of the file in parallel to the CDA-AMC’s health technology assessment (HTA) review process, rather than subsequently. Electing to file the HTA submission pre-NOC could have further accelerated timelines. No acceleration in each agency’s review time was observed. Conclusions: Participation in the TLR-pTAP pathway can help mitigate concerns over uncertainties associated with novel therapies while providing timelier access for patients with life-threatening diseases. Full article

Our knowledge of the ecology of non-marine Ostracoda inhabiting endorheic wetlands (pans) of the semi-arid regions of South Africa is very scarce. The present study investigates the distribution of ostracod species in grass, open, and salt pans in the central part of the North West province and tests ostracod response to abiotic and biotic predictor variables operating at a local scale. Distance-based linear models revealed three variables (pan type, water electrical conductivity and abundance of macroinvertebrate predators, and collector-gatherers) that best explained variation in the ostracod dataset. Ostracod assemblages from the three studied pan types differed by the dominance structure rather than by the species composition. Salt pans with high conductivity and high ratio of predaceous macroinvertebrates were dominated by Heterocypris giesbrechti, with accessory presence of Plesiocypridopsis newtoni. In open pans with low conductivities and the lowest ratio of predators (but highest ratio of collector-gatherers) Potamocypris mastigophora was typically a dominant species, while in grass pans, all the three mentioned species had similar relative abundances. Although our findings lend provisional support to some models of ostracod assemblage diversity across different pan types, more studies replicating endorheic depression wetlands in other regions are required before generalizations can be made. Full article

Hepatocellular carcinoma (HCC) is a primary liver tumor with high lethality and increasing incidence worldwide. While tumor resection or liver transplantation is effective in the early stages of the disease, the therapeutic options for advanced HCC remain limited and the benefits are temporary. Thus, novel therapeutic targets and more efficacious treatments against this deadly cancer are urgently needed. Here, we investigated the pathogenetic and therapeutic role of eukaryotic initiation factor 4A1 (eIF4A1) in this tumor type. We observed consistent eIF4A1 upregulation in HCC lesions compared with non-tumorous surrounding liver tissues. In addition, eIF4A1 levels were negatively correlated with the prognosis of HCC patients. In HCC lines, the exposure to various eIF4A inhibitors triggered a remarkable decline in proliferation and augmented apoptosis, paralleled by the inhibition of several oncogenic pathways. Significantly, anti-growth effects were achieved at nanomolar concentrations of the eIF4A1 inhibitors and were further increased by the simultaneous administration of the pan mTOR inhibitor, Rapalink-1. In conclusion, our results highlight the pathogenetic relevance of eIF4A1 in HCC and recommend further evaluation of the potential usefulness of pharmacological combinations based on eIF4A and mTOR inhibitors in treating this aggressive tumor. Full article

Secondary lymphoid tissues play a major role in the human immune response to P. falciparum infection. Previous studies have shown that acute falciparum malaria is associated with marked perturbations of the cellular immune system characterized by lowered frequency and absolute number of circulating T cell subsets. A temporary relocation of T cells, possibly by infiltration to secondary lymphoid tissue, or their permanent loss through apoptosis, are two proposed explanations for this observation. We conducted the present study to determine the phenotype of lymphocyte subsets that accumulate in the lymph node and spleen during acute stages of falciparum malaria infection in Malawian children, and to test the hypothesis that lymphocytes are relocated to lymphoid tissues during acute infection. We stained tissue sections from children who had died of the two common clinical forms of severe malaria in Malawi, namely severe malarial anemia (SMA, n = 1) and cerebral malaria (CM, n = 3), and used tissue sections from pediatric patients who had died of non-malaria sepsis (n = 2) as controls. Both lymph node and spleen tissue (red pulp) sections from CM patients had higher percentages of T cells (CD4⁺ and CD8⁺) compared to the SMA patient. In the latter, we observed a higher percentage of CD20⁺ B cells in the lymph nodes compared to CM patients, whereas the opposite was observed in the spleen. Both lymph node and spleen sections from CM patients had increased percentages of CD69⁺ and CD45RO⁺ cells compared to tissue sections from the SMA patient. These results support the hypothesis that the relocation of lymphocytes to spleen and lymph node may contribute to the pan-lymphopenia observed in acute CM. Full article

This study aimed to classify an urban area and its surrounding objects after the destructive M7.3 Kermanshah earthquake (12 November 2017) in the west of Iran using very high-resolution (VHR) post-event WorldView-2 images and object-based image analysis (OBIA) methods. The spatial resolution of multispectral (MS) bands (~2 m) was first improved using a pan-sharpening technique that provides a solution by fusing the information of the panchromatic (PAN) and MS bands to generate pan-sharpened images with a spatial resolution of about 50 cm. After applying a segmentation procedure, the classification step was considered as the main process of extracting the aimed features. The aforementioned classification method includes applying spectral and shape indices. Then, the classes were defined as follows: type 1 (settlement area) was collapsed areas, non-collapsed areas, and camps; type 2 (vegetation area) was orchards, cultivated areas, and urban green spaces; and type 3 (miscellaneous area) was rocks, rivers, and bare lands. As OBIA results in the integration of the spatial characteristics of the image object, we also aimed to evaluate the efficiency of object-based features for damage assessment within the semi-automated approach. For this goal, image context assessment algorithms (e.g., textural parameters, shape, and compactness) together with spectral information (e.g., brightness and standard deviation) were applied within the integrated approach. The classification results were satisfactory when compared with the reference map for collapsed buildings provided by UNITAR (the United Nations Institute for Training and Research). In addition, the number of temporary camps was counted after applying OBIA, indicating that 10,249 tents or temporary shelters were established for homeless people up to 17 November 2018. Based on the total damaged population, the essential resources such as emergency equipment, canned food and water bottles can be estimated. The research makes a significant contribution to the development of remote sensing science by means of applying different object-based image-analyzing techniques and evaluating their efficiency within the semi-automated approach, which, accordingly, supports the efficient application of these methods to other worldwide case studies. Full article

In August 2015, Malaysia experienced an outbreak of acute respiratory disease in racehorses. Clinical signs observed were consistent with equine influenza (EI) infection. The index cases were horses recently imported from New Zealand. Rapid control measures, including temporary cancellation of racing, were implemented to minimize the impact of the outbreak. By November, the disease outbreak was resolved, and movement restrictions were lifted. The aim of this study was to confirm the clinical diagnosis and characterize the causal virus. A pan-reactive influenza type A real-time RT-PCR was used for confirmatory diagnosis. Antigenic characterization by haemagglutinin inhibition using a panel of specific ferret antisera indicated that the causal virus belonged to clade 1 of the H3N8 Florida sub-lineage. The genetic characterization was achieved by the whole genome sequencing of positive nasal swabs from clinically affected animals. Pylogenetic analysis of the haemagglutinin (HA) and neuraminidase (NA) genes demonstrated ≥99% homology with several EI strains that had recently circulated in the USA and Japan. The antigenic and genetic characterization did not indicate that the current World Organisation for Animal Health (OIE) recommendations for EI vaccine composition required modification. Full article

This study aimed to investigate the airborne release of N-nitrosodimethylamine (NDMA) as a result of the dry-heat cooking of some meats using charcoal grilling and pan-broiling methods. Three types of meat (beef sirloin, pork belly, and duck) were chosen and cooked in a temporary building using the above methods. Air samples were collected in Thermosorb-N cartridges, which were qualitatively and quantitatively analyzed for NDMA using ultra-high performance liquid chromatography–mass spectrometry and high-performance liquid chromatography–fluorescence detection, respectively. Overall, the charcoal grilling method showed higher average NDMA concentrations than the pan-broiling method for all types of meat. The highest average concentration was observed for charcoal-grilled beef sirloin (410 ng/m³) followed by pork belly, suggesting that meat protein content and cooking duration are important determinants of NDMA formation. Cancer risk assessment showed that the charcoal grilling of such meats can pose an additional cancer risk for restaurant customers. Full article