Climate change adaptation through coastal and use management: The context of environmental justice

Despite an increasing literary focus on climate change adaptation, the facilitation of this adaptation is occurring on a limited basis (Adger et al. 2007) .This limited basis is not necessarily due to inability; rather, a lack of comprehensive cost estimates of all options specifically hinders adaptation in vulnerable communities (Adger et al. 2007). Specifically the estimated cost of the climate change impact of sea-level rise is continually increasing due to both increasing rates and the resulting multiplicative impact of coastal erosion (Karl et al., 2009, Zhang et al., 2004) Based on the 2007 Intergovernmental Panel on Climate Change report, minority groups and small island nations have been identified within these vulnerable communities. Therefore the development of adaptation policies requires the engagement of these communities. State examples of sea-level rise adaptation through land use planning mechanisms such as land acquisition programs (New Jersey) and the establishment of rolling easements (Texas) are evidence that although obscured, adaptation opportunities are being acted upon (Easterling et al., 2004, Adger et al.2007). (PDF contains 4 pages

Detection of disease change using a biological marker and clinical application: CA125 in ovarian cancer patients

In Oncology drug development, the great majority of phase 3 trials are negative.. New strategies are required to rapidly identify novel agents prior to large randomised trials. The CA125 doubling trial successfully showed that an effective drug could be identified more efficiently by testing whether the rate of increase in the tumour marker CA125 decreased after starting the novel agent, at a point identified by CA125 rising to four times it’s nadir level. However efficiency could be improved, if more patients could be included. This work explores identifying an earlier effective starting point by analysing the time course of CA125 rise.Non peer reviewe

Survival Outcomes After High-dose Chemotherapy and Stem Cell Transplantation in the Salvage Setting for Relapsed or Refractory Germ Cell Cancers

© 2020 The Author(s). The unrestricted non-commercial use, distribution and reproduction in any medium of CGP articles for academic reasons is allowed, provided that the original work is properly cited.Background/Aim: High-dose chemotherapy (HDCT) and stem cell transplantation (SCT) have been established as the standard of care in patients with relapsed germ cell tumours (GCTs). We evaluated the safety, efficacy and tolerability of HDCT/ SCT in patients with relapsed GCTs. Patients and Methods: Twenty-eight patients with relapsed GCTs, treated with HDCT, were included in this study. The conditioning regime was carboplatin, etoposide, cyclophosphamide and paclitaxel. Clinical, radiological imaging and tumour markers determined treatment outcomes. Results: Median age was 35 years (range=21-57 years) with 26 males and 2 females. Median time to first relapse was 6 months. Median time to progression after 2nd line chemotherapy was 17.3 months. Fourteen patients had peripheral neurotoxicity (≥Grade 2) (50%), 4 patients developed renal failure, 5 had ototoxicity (≥Grade 2) and 1 patient developed acute myeloid leukaemia. Median survival was 62 months and 16 patients (57%) are in clinical follow-up with surveillance. Conclusion: In relapsed GCT patients, median survival may exceed 5 years post-HDCT and SCT.Peer reviewe

Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer

Objective: New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis. Methods: Asymptomatic patients with relapsed ovarian cancer who had responded to chemotherapy were enrolled and had CA125 measurements taken every 4 weeks, then more frequently when rising. Once levels reached 4 times the upper limit of normal or nadir, they started continuous tamoxifen 20 mg daily, as well as fortnightly CA125 measurements until symptomatic progression. Because of the potentially nonlinear relationship of CA125 over time, it was felt that to enable normal approximations to be utilized a natural logarithmic standard transformation [ln(CA125)] was the most suitable to improve linearity above the common logarithmic transformation to base 10. Results: From 235 recruited patients, 81 started tamoxifen and had at least 4 CA125 measurements taken before and 4 CA125 measurements taken after starting tamoxifen, respectively. The mean regression slopes from using at least 4 1n(CA125) measurements immediately before and after starting tamoxifen were 0I0149 and 0I0093 [ln(CA125)/d], respectively. This difference is statistically significant, P = 0I001. Therefore, in a future trial with a novel agent, at least as effective as tamoxifen, using this effect size, the number of evaluable patients needed, at significance level of 5% and power of 80%, is 56. Conclusions: Further validation of this methodology is required, but there is potential to use comparison of mean regression slopes of ln(CA125) as an interim analysis measure of efficacy for novel cytostatic agents in relapsed ovarian cancer.Peer reviewedFinal Accepted Versio

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

Ovarian cancer (OvCa) is one of the most lethal forms of gynaecological malignancy. Altered energy metabolism and increased aerobic glycolysis in OvCa are hallmarks that demand attention. The glucogenic hormone asprosin is often dysregulated in metabolic disorders such as insulin resistance, diabetes (type 2 and gestational), and preeclampsia. Despite association with metabolic disorders, its role in energy metabolism within the tumour microenvironment is yet to be explored. Here, we study the role of asprosin in OvCa using transcriptomics and expand on functional studies with clinical samples. RNA sequencing, functional gene enrichment analysis, Western blotting and ImageStream. Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene regulatory changes, at 4 and 12 h respectively, when compared with control samples ( < 0.05 and Log2FC > 1). In addition to energy metabolism and glucose-related pathways, asprosin was shown to alter pathways associated with cell communication, TGF-β signalling, and cell proliferation. Moreover, asprosin was shown to induce phosphorylation of ERK1/2 in the same in vitro model. Using liquid biopsies, we also report for novel expression of asprosin's predicted receptors OR4M1 and TLR4 in cancer-associated circulating cells; with significant reduction seen between pre-chemotherapy and end of first line chemotherapy, in addition to patients under maintenance with bevacizumab +/- olaparib for OR4M1. In relation to OvCa, asprosin appears to regulate numerous signalling pathways in-vitro. The prognostic potential of OR4M1 in liquid biopsies should also be explored further

Neuropilin‑1 as a new potential SARS‑CoV‑2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID‑19

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the cause of the new viral infectious disease (coronavirus disease 2019; COVID-19). Emerging evidence indicates that COVID-19 may be associated with a wide spectrum of neurological symptoms and complications with central nervous system (CNS) involvement. It is now well-established that entry of SARS-CoV-2 into host cells is facilitated by its spike proteins mainly through binding to the angiotensin-converting enzyme 2 (ACE-2). Preclinical studies have suggested that neuropilin-1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVID-19 by enhancing the entry of SARS-CoV-2 into the brain through the olfactory epithelium. In the present study, we expand on these findings and demonstrate that the NRP1 is also expressed in the CNS, including olfactory-related regions such as the olfactory tubercles and paraolfactory gyri. This furthers supports the potential role of NRP1 as an additional SARS-CoV-2 infection mediator implicated in the neurologic manifestations of COVID-19. Accordingly, the neurotropism of SARS-CoV-2 via NRP1-expressing cells in the CNS merits further investigation

Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer

Importance: The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event. Objective: To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer. Design, setting, and participants: ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019. Exposures: The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period. Main outcomes and measures: The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism. Results: A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P < .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively. Conclusions and relevance: This study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis