A forum on the Zika virus

Luciana Brondi – ORCID: 0000-0001-6221-4440 https://orcid.org/0000-0001-6221-4440Item not available in this repository.http://somatosphere.net/2016/a-forum-on-the-zika-virus.html

Data mining in biomedicine : current applications and further directions for research

Author name used in this manuscript: S. K. KwokAuthor name used in this manuscript: A. H. C. Tsang2009-2010 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Prospective memory in non-psychotic first-degree relatives of patients with schizophrenia

Although a number of studies have found prospective memory (PM) impairment in patients with schizophrenia, very little is known about the PM performance in non-psychotic relatives of these patients. The current study aimed to explore the PM performance in non-psychotic first-degree relatives of these patients. Two groups of participants (26 non-psychotic first-degree relatives of schizophrenia patients and 26 healthy comparison participants) were administered three PM tasks (time-, event-, and activity-based) and a set of neurocognitive tests. Results showed that the relatives performed significantly worse than the comparisons on most indices of the PM tasks, with a similar pattern of impairment found in other neurocognitive measures. Together with findings from previous studies, results of the current study suggest that PM may be a potential endophenotype for schizophrenia. (C) 2009 Elsevier Ireland Ltd. All rights reserved.</p

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Technocratic tuberculosis control: health professionals at the interstices of DOTS in Shanghai, China

This thesis explores the entangled nature of human and non-human agencies in the making and maintaining of a global health programme in a local setting. Specifically, it investigates how public health professionals engage with and enact the technocratic management of tuberculosis control as per the DOTS approach in contemporary Shanghai. My research is based on a fourteen-month internship with the Shanghai Centre for Disease Control and Prevention (SCDC) and examines the mechanics of tuberculosis control in the metropolis at the municipal, district and community levels. In this thesis, I show how non-human agents intrinsic to the functioning of DOTS – protocols, standards, numbers, technology, concepts such as ‘compliance’ and ‘scale’, inter alia – are both useful and risky. They bring consistency and accountability, assert compliance and conformity, but also set limitations for the project of recovery and cure. As such, considerable maodun (矛盾) or contradictions arise when technocratic policy and sick patients meet, and I demonstrate how these moments offer rich opportunities for understanding how DOTS operates in a local context. Public health professionals are positioned in between policy and patients, and both occupy and constitute the interstices that separate and connect the two. I argue that they negotiate these moments of maodun to make DOTS fit for human use. I further suggest that they do so through their subjective engagement, exertion of emotional labour, and exercise of discretion in managing technocratic tuberculosis control. Entangled with the influence of non-humans, this thesis argues that the choices and actions of public health professionals inform the formation of their own interstitiality and, recursively, make and shape the nature of tuberculosis and its control for patients in Shanghai, for China, and for the Global Health project more widely. Rooted in medical anthropology and the Shanghainese experience, this thesis contributes to wider discussions on the human and non-human in the co-production of knowledge, and the pivotal role played by individuals to exert profound influence within the larger and technocratic

The status of natural succession in lowland secondary forests of Hong Kong

Hong Kong has undergone a long history of deforestation for more than 1, 000 years. No primary forest can now be found in Hong Kong and most of the secondary forests have been restored through natural succession after the Second World War. By knowing the most updated secondary forest succession status in Hong Kong, a more proactive management plan can be worked out to have a better forest restoration strategy. Forest Dynamic Plots are large forest plots which can provide information about species composition, changes in the species spatial arrangement over time and population growth. In this study, the successional status of two local natural lowland secondary forests of different ages are evaluated by using Forest Dynamic Plot data. These two 1 hectare size plots are located at Shek Kong and Tai Po Kau Nature Reserve respectively. The data collected is analyzed and compared with another Forest Dynamic Plot in Dinghushan National Nature Reserve in Guangdong, China which is an old-growth lowland forest. It is within the same biogeographic region with Hong Kong. Tree surveys were conducted in these plots. All the trees and shrubs with diameter at breast height equal or larger than 10mm were tagged, measured, identified and mapped. In the 20-year old Shek Kong Plot, a total of 10378 individuals of 62 native species of woody shrubs or trees were recorded. The dominant species are Litsea rotundifolia var. oblongifolia, Psychotria asiatica and Aporusa dioica with an importance value of 20.463, 11.725 and 6.574 respectively. The Shek Kong Plot is dominated by shade-intolerant shrub or pioneer species. The Shek Kong Plot is still in early secondary stage or entering the stem exclusion stage. The 60-year old Tai Po Kau Plot has a total of 5172 individuals of 77 species. The Tai Po Kau Plot has much lower stem density than the Shek Kong Plot but with higher species diversity. The top three dominant species in Tai Po Kau Plot are Machilus chekiangensis, Psychotria asiatica and Diospyros morrisiana, with an importance value of 23.538, 15.321 and 7.652 respectively. Although the Tai Po Kau Plot is more dominated by tree species, when it is compared with the Dinghushan Plot, the shade-tolerant climax species are still in low intensity. Thus, Tai Po Kau is not yet an old-growth or mature forest. It is now in understory reintiaition stage or late secondary stage and more shade-tolerant species are needed to move to the mature forest stage. To facilitate the forest succession process, it is recommended to have more studies on the distribution pattern and seed dispersal mechanism of shade-tolerant species. Feasibility study of reintroduction of relevant seed dispersal agents such as rodents from Southern China could be a more proactive management to facilitate the process.published_or_final_versionEnvironmental ManagementMasterMaster of Science in Environmental Managemen