Megadroughts in the Common Era and the Anthropocene

Exceptional drought events, known as megadroughts, have occurred on every continent outside Antarctica over the past ~2,000 years, causing major ecological and societal disturbances. In this Review, we discuss shared causes and features of Common Era (Year 1–present) and future megadroughts. Decadal variations in sea surface temperatures are the primary driver of megadroughts, with secondary contributions from radiative forcing and land–atmosphere interactions. Anthropogenic climate change has intensified ongoing megadroughts in south-western North America and across Chile and Argentina. Future megadroughts will be substantially warmer than past events, with this warming driving projected increases in megadrought risk and severity across many regions, including western North America, Central America, Europe and the Mediterranean, extratropical South America, and Australia. However, several knowledge gaps currently undermine confidence in understanding past and future megadroughts. These gaps include a paucity of high-resolution palaeoclimate information over Africa, tropical South America and other regions; incomplete representations of internal variability and land surface processes in climate models; and the undetermined capacity of water-resource management systems to mitigate megadrought impacts. Addressing these deficiencies will be crucial for increasing confidence in projections of future megadrought risk and for resiliency planning

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Prevalence and determinants of frailty in the absence of disability among older population: a cross sectional study from rural communities in Nepal

BACKGROUND: Longevity and frailty have significant implications for healthcare delivery. They increase demands for healthcare service and surge risk of hospitalization. Despite gaining global attention, determinants of frailty have remained unmeasured in the rural community settings in Nepal. This study aimed to address this gap by accessing the prevalence and determinants of frailty in the absence of disability among older population living in rural communities in eastern Nepal. METHODS: We conducted a cross-sectional analytical study of 794 older adults aged ≥60 living in the rural part of Sunsari and Morang district of eastern Nepal between January and April in 2018. Multi-stage cluster sampling was applied to recruit the study participants. Study measures included socio-demographics; Frail Non-disabled scale (FiND) measuring frailty, Barthel\u27s Index measuring basic activities of daily living and Geriatric depression scale. Determinants of frailty in the absence of disability were identified using generalized estimating equation (GEE). RESULTS: About 65% of the participants self-reported the presence of frailty in the absence of disability. In the adjusted models, those from underprivileged ethnic groups, lack of daily physical exercise, presence of depressive symptoms and those not getting enough social support from family were found to be significantly associated with frailty among older participants. CONCLUSIONS: The prevalence of frailty in the absence of disability was high among rural community old population living in eastern Nepal. Our findings suggest that need of frailty awareness (both for clinicians and general public), so as to avoid negative consequences. To reduce the healthcare burden early screening frailty in primary care has potentials to prevent implications of frailty in Nepal

Towards a Security Enhanced Virtualised Network Infrastructure for Internet of Medical Things (IoMT)

Internet of Medical Things (IoMT) are getting popular in the smart healthcare domain. These devices are resource-constrained and are vulnerable to attack. As the IoMTs are connected to the healthcare network infrastructure, it becomes the primary target of the adversary due to weak security and privacy measures. In this regard, this paper proposes a security architecture for smart healthcare network infrastructures. The architecture uses various security components or services that are developed and deployed as virtual network functions. This makes the security architecture ready for future network frameworks such as OpenMANO. Besides, in this security architecture, only authenticated and trusted IoMTs serve the patients along with an encryption-based communication protocol, thus creating a secure, privacy-preserving and trusted healthcare network infrastructure

The Dendroclimatological Potential of Common Yew (Taxus baccata L.) from Southern Azerbaijan

Paleoclimate reconstructions from tree rings have so far been restricted to the western and northern Caucasus, and there have been no published tree-ring studies on any topic from the Republic of Azerbaijan in the eastern Caucasus. Here we report the first tree-ring study conducted in Azerbaijan and show that, in the southern part of the country, the common yew (Taxus baccata L.) has potential to provide annually-resolved paleoclimate information on temperature variability during winter. Dur- ing the summers of 2016 and 2017, we obtained single cores from 23 yews in the Hyrcanian forests of southern Azerbaijan, near the village of Hamarat (Lerik district). The oldest yew had an inner ring date of C.E. 1867, but most other trees at this location began growing in the early 20th Century. Growth at the Lerik site is primarily and positively influenced by winter temperatures and, to a lesser degree, precipitation during summer and early autumn. Future collections of tree-ring widths from T. baccata in Azerbaijan could fill important geographic and seasonal gaps in our current paleotemperature network, and also provide useful information regarding the pace and potential impacts of wintertime warming in this region

Prevalence and determinants of frailty in the absence of disability among older population: a cross sectional study from rural communities in Nepal

Background: Longevity and frailty have significant implications for healthcare delivery. They increase demands for healthcare service and surge risk of hospitalization. Despite gaining global attention, determinants of frailty have remained unmeasured in the rural community settings in Nepal. This study aimed to address this gap by accessing the prevalence and determinants of frailty in the absence of disability among older population living in rural communities in eastern Nepal. Methods: We conducted a cross-sectional analytical study of 794 older adults aged ≥60 living in the rural part of Sunsari and Morang district of eastern Nepal between January and April in 2018. Multi-stage cluster sampling was applied to recruit the study participants. Study measures included socio-demographics; Frail Non-disabled scale (FiND) measuring frailty, Barthel's Index measuring basic activities of daily living and Geriatric depression scale. Determinants of frailty in the absence of disability were identified using generalized estimating equation (GEE). Results: About 65% of the participants self-reported the presence of frailty in the absence of disability. In the adjusted models, those from underprivileged ethnic groups, lack of daily physical exercise, presence of depressive symptoms and those not getting enough social support from family were found to be significantly associated with frailty among older participants. Conclusions: The prevalence of frailty in the absence of disability was high among rural community old population living in eastern Nepal. Our findings suggest that need of frailty awareness (both for clinicians and general public), so as to avoid negative consequences. To reduce the healthcare burden early screening frailty in primary care has potentials to prevent implications of frailty in Nepal