Vibrational Spectroscopy for Pathology from Biochemical Analysis to Diagnostic Tool

Cervical cancer is the second most common cancer in women worldwide with 80% of cases arising in the developing world. The mortality associated with cervical cancer can be reduced if this disease is detected at the early stages of development or at the pre-malignant state (cervical intra-epithelial neoplasia, CIN). The aim of this study was to investigate the potential of Raman spectroscopy as a diagnostic tool to detect biochemical changes accompanying cervical cancer progression. Raman spectra were acquired from proteins, nucleic acids, lipids and carbohydrates in order to gain an insight into the biochemical composition of cells and tissues. Spectra were also obtained from histological samples of normal, CIN and invasive carcinoma tissue from 40 patients. Multivariate analysis of the spectra was carried out to develop a classification model to discriminate normal from abnormal tissue. The results show that Raman spectroscopy displays a high sensitivity to biochemical changes in tissue during disease progression resulting in an exceptional prediction accuracy when discriminating between normal cervical tissue, invasive carcinoma and cervical intra-epithelial neoplasia (CIN). Raman spectroscopy shows enormous clinical potential as a rapid non invasive diagnostic tool for cervical and other cancers

Perspectives of pharmacists on facilitating experiential learning placements for pharmacy students in non-patient facing settings

Full text available via ShareLink until August 07 2020: https://authors.elsevier.com/a/1bFq96gprIBGQ%7EIntroduction: Recently, the model of pharmacy education in Ireland changed to a five-year pharmacy degree, with three distinct blocks of experimental placements dispersed throughout the degree. The United Kingdom is also considering the introduction of a similar five-year pharmacy degree, while the United States is looking to further expand non-clinical experiential learning opportunities. This study was carried out to ascertain the perspectives of pharmacists working in non-patient facing roles on the barriers to and facilitators of placements to aid in identifying placement recruitment strategies for non-patient facing placements. Methods: A questionnaire was distributed to pharmacists employed in non-patient facing settings, including in pharmaceutical industry, education, and regulation. Quantitative responses were analyzed using descriptive statistics, while qualitative questions were analyzed thematically. Results: Regardless of experience in the practice setting or supervision, the majority expressed a preference for offering paid placements of six months' duration. There was divided opinion regarding whether students should be given study leave, whether the student's supervisor should be a pharmacist, and whether students should undertake specialized postgraduate training. The main barriers to placements were time, the placement structure, availability of suitable projects or supervisors, and awareness of placement opportunities. Prior experience in the practice area, developing the talent pipeline, and personal interests were all placement facilitators. Conclusions: Given the increasing roles for pharmacists in non-patient facing practice settings, this study highlights the importance of stakeholder involvement during the implementation of a new model of education to ensure that placements in all settings are feasible

S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC

National CO\u3csub\u3e2\u3c/sub\u3e budgets (2015-2020) inferred from atmospheric CO\u3csub\u3e2\u3c/sub\u3e observations in support of the global stocktake

Accurate accounting of emissions and removals of CO2 is critical for the planning and verification of emission reduction targets in support of the Paris Agreement. Here, we present a pilot dataset of country-specific net carbon exchange (NCE; fossil plus terrestrial ecosystem fluxes) and terrestrial carbon stock changes aimed at informing countries\u27 carbon budgets. These estimates are based on top-down NCE outputs from the v10 Orbiting Carbon Observatory (OCO-2) modeling intercomparison project (MIP), wherein an ensemble of inverse modeling groups conducted standardized experiments assimilating OCO-2 column-Averaged dry-Air mole fraction (XCO2) retrievals (ACOS v10), in situ CO2 measurements or combinations of these data. The v10 OCO-2 MIP NCE estimates are combined with bottom-up estimates of fossil fuel emissions and lateral carbon fluxes to estimate changes in terrestrial carbon stocks, which are impacted by anthropogenic and natural drivers. These flux and stock change estimates are reported annually (2015-2020) as both a global 1gg×g1g gridded dataset and a country-level dataset and are available for download from the Committee on Earth Observation Satellites\u27 (CEOS) website: 10.48588/npf6-sw92 . Across the v10 OCO-2 MIP experiments, we obtain increases in the ensemble median terrestrial carbon stocks of 3.29-4.58gPgCO2yr-1 (0.90-1.25gPgCyr-1). This is a result of broad increases in terrestrial carbon stocks across the northern extratropics, while the tropics generally have stock losses but with considerable regional variability and differences between v10 OCO-2 MIP experiments. We discuss the state of the science for tracking emissions and removals using top-down methods, including current limitations and future developments towards top-down monitoring and verification systems

A deep dive into the ecology of Gamay (Botany Bay, Australia): current knowledge and future priorities for this highly modified coastal waterway

Context: Gamay is a coastal waterway of immense social, cultural and ecological value. Since European settlement, it has become a hub for industrialisation and human modification. There is growing desire for ecosystem-level management of urban waterways, but such efforts are often challenged by a lack of integrated knowledge. Aim and methods: We systematically reviewed published literature and traditional ecological knowledge (TEK), and consulted scientists to produce a review of Gamay that synthesises published knowledge of Gamay’s aquatic ecosystem to identify knowledge gaps and future research opportunities. Key results: We found 577 published resources on Gamay, of which over 70% focused on ecology. Intertidal rocky shores were the most studied habitat, focusing on invertebrate communities. Few studies considered multiple habitats or taxa. Studies investigating cumulative human impacts, long-term trends and habitat connectivity are lacking, and the broader ecological role of artificial substrate as habitat in Gamay is poorly understood. TEK of Gamay remains a significant knowledge gap. Habitat restoration has shown promising results and could provide opportunities to improve affected habitats in the future. Conclusion and implications: This review highlights the extensive amount of knowledge that exists for Gamay, but also identifies key gaps that need to be filled for effective management

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application

National CO2 budgets (2015–2020) inferred from atmospheric CO2 observations in support of the Global Stocktake

Accurate accounting of emissions and removals of CO2 is critical for the planning and verification of emission reduction targets in support of the Paris Agreement. Here, we present a pilot dataset of country-specific net carbon exchange (NCE; fossil plus terrestrial ecosystem fluxes) and terrestrial carbon stock changes aimed at informing countries’ carbon budgets. These estimates are based on "top-down" NCE outputs from the v10 Orbiting Carbon Observatory (OCO-2) modeling intercomparison project (MIP), wherein an ensemble of inverse modeling groups conducted standardized experiments assimilating OCO-2 column-averaged dry-air mole fraction (XCO2) retrievals (ACOS v10), in situ CO2 measurements, or combinations of these data. The v10 OCO-2 MIP NCE estimates are combined with "bottom-up" estimates of fossil fuel emissions and lateral carbon fluxes to estimate changes in terrestrial carbon stocks, which are impacted by anthropogenic and natural drivers. These flux and stock change estimates are reported annually (2015–2020) as both a global 1° × 1° gridded dataset and as a country-level dataset. Across the v10 OCO-2 MIP experiments, we obtain increases in the ensemble median terrestrial carbon stocks of 3.29–4.58 PgCO2 yr-1 (0.90–1.25 PgC yr-1). This is a result of broad increases in terrestrial carbon stocks across the northern extratropics, while the tropics generally have stock losses but with considerable regional variability and differences between v10 OCO-2 MIP experiments. We discuss the state of the science for tracking emissions and removals using top-down methods, including current limitations and future developments towards top-down monitoring and verification systems