Named Entity Recognition in Chinese Clinical Text

Objective: Named entity recognition (NER) is one of the fundamental tasks in natural language processing (NLP). In the medical domain, there have been a number of studies on NER in English clinical notes; however, very limited NER research has been done on clinical notes written in Chinese. The goal of this study is to develop corpora, methods, and systems for NER in Chinese clinical text. Materials and methods: To study entities in Chinese clinical text, we started with building annotated clinical corpora in Chinese. We developed an NER annotation guideline in Chinese by extending the one used in the 2010 i2b2 NLP challenge. We randomly selected 400 admission notes and 400 discharge summaries from Peking Union Medical College Hospital (PUMCH) in China. For each note, four types of entities including clinical problems, procedures, labs, and medications were annotated according to the developed guideline. In addition, an annotation tool was developed to assist two MD students to annotate Chinese clinical documents. A comparison of entity distribution between Chinese and English clinical notes (646 English and 400 Chinese discharge summaries) was performed using the annotated corpora, to identify the important features for NER. In the NER study, two-thirds of the 400 notes were used for training the NER systems and one-third were used for testing. We investigated the effects of different types of features including bag-of-characters, word segmentation, part-of-speech, and section information, with different machine learning (ML) algorithms including Conditional Random Fields (CRF), Support Vector Machines (SVM), Maximum Entropy (ME), and Structural Support Vector Machines (SSVM) on the Chinese clinical NER task. All classifiers were trained on the training dataset, evaluated on the test set, and microaveraged precision, recall, and F-measure were reported. Results: Our evaluation on the independent test set showed that most types of features were beneficial to Chinese NER systems, although the improvements were limited. By combining word segmentation and section information, the system achieved the highest performance, indicating that these two types of features are complementary to each other. When the same types of optimized features were used, CRF and SSVM outperformed SVM and ME. More specifically, SSVM reached the highest performance among the four algorithms, with F-measures of 93.51% and 90.01% for admission notes and discharge summaries respectively. Conclusions: In this study, we created large annotated datasets of Chinese admission notes and discharge summaries and then systematically evaluated different types of features (e.g., syntactic, semantic, and segmentation information) and four ML algorithms including CRF, SVM, SSVM, and ME for clinical NER in Chinese. To the best of our knowledge, this is one of the earliest comprehensive effort in Chinese clinical NER research and we believe it will provide valuable insights to NLP research in Chinese clinical text. Our results suggest that both word segmentation and section information improves NER in Chinese clinical text, and SSVM, a recent sequential labelling algorithm, outperformed CRF and other classification algorithms. Our best system achieved F-measures of 90.01% and 93.52% on Chinese discharge summaries and admission notes, respectively, indicating a promising start on Chinese NLP research

Improving our understanding of childhood psoriasis: Identifying opportunities for early intervention for the prevention of long-term harm

1.1 Introduction Psoriasis is an immune-mediated chronic inflammatory disease affecting the skin and joints of adults and children. This PhD focused on psoriasis in children because it is especially for this age group that both a research need and an opportunity to improve long-term health outcomes exist. There is a deficiency of paediatric specific research to guide optimal management and, for many individuals, the persistence of psoriasis into adulthood has a negative cumulative effect over their lifetime. Difficulties can arise because of the physical, psychological, and social burden of psoriasis, including the development of psoriatic arthritis. 1.2 Research aim The aim of this research was to identify opportunities to intervene early in the disease course of children with psoriasis and juvenile psoriatic arthritis, in order to prevent long-term harm from these conditions. Specifically the research aims of each study were: 1. To determine current clinical practice in the assessment and management of childhood psoriasis. 2. To understand current clinical practice in the assessment of juvenile psoriatic arthritis and psoriasis. 3. To map the evidence and identify research gaps in the epidemiology of childhood psoriasis. 4. To identify studies which have developed or validated diagnostic criteria for psoriasis. 5. To derive expert agreed diagnostic criteria for plaque psoriasis in children. 6. To design a diagnostic accuracy study to develop DIagnostic criteria for PSOriasis in Children (DIPSOC Study) 1.3 Methods The initial studies focused on identifying deficiencies in current practice and exploring barriers in the detection of psoriasis and juvenile psoriatic arthritis. This research was undertaken as a multi-centre audit and case-note review, and qualitative descriptive interviews with paediatric rheumatologists and dermatologists. Framework and thematic content analysis were used to ascertain and explore the approach clinicians’ take to assess skin and joint disease. The subsequent studies have mapped the volume, nature, and characteristics of epidemiological studies and appraised the literature to inform the development of diagnostic criteria for psoriasis in children. This research was undertaken as a scoping review on the epidemiology of childhood psoriasis and a systematic review on diagnostic criteria for psoriasis. The studies in the systematic review were appraised for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. The final studies focused on developing diagnostic criteria for psoriasis in children. An electronic Delphi (eDelphi) consensus study with the International Psoriasis Council (IPC) used sequential online questionnaires and scoring to reach agreement on a list of expert-derived criteria. These five studies informed the design of a multi-centre case-control diagnostic accuracy study (DIPSOC study) to test the consensus agreed criteria and develop the best predictive criteria. 1.4 Results The audit of the care of 285 children with psoriasis showed that compliance with national guidelines was variable. Only half of children were assessed annually for juvenile psoriatic arthritis and a third of children with psoriasis were potentially misdiagnosed with having other skin diseases in primary care. Exploring this further, paediatric rheumatologists’ and dermatologists’ current approach for assessing skin and joint disease, respectively, may not detect psoriasis and juvenile psoriatic arthritis. Reviewing the evidence base, most epidemiological data originates from case-series and cross-sectional studies, and there were few case-control and cohort studies investigating risk factors for disease onset, comorbidities, and long-term health outcomes in paediatric psoriasis. This work highlighted a need to improve the recognition of psoriasis in children and for new studies using standardised methodologies and definitions. Currently, no clinical examination-based diagnostic criteria for psoriasis have been developed, tested, or validated. To address this evidence gap, experts collectively agreed on 16 diagnostic features, divided into three major and thirteen minor criteria, which are important for the clinical diagnosis of plaque psoriasis in children. These consensus agreed criteria will be tested in the DIPSOC study. The design of DIPSOC aims to minimise bias in the four key domains proposed by the QUADAS-2 tool, but uses a case-control design to ensure the recruitment target is feasible within the resources available. 1.5 Discussion The research in this PhD makes an important contribution to the field of paediatric psoriasis and culminates in the design of the DIPSOC study to test and refine a list of diagnostic criteria for psoriasis in children. The criteria are intended to improve the recognition and early diagnosis of psoriasis in children, as well as offer a standardised disease definition for clinical trials and observational research. Improved diagnostic accuracy and increasing the quality of evidence from research studies will provide opportunities for early intervention to prevent long-term harm in children with psoriasis

An investigation of the pharmacological effects of Nao Xin Qing (NXQ), a standardised herbal extract, for ischaemic stroke : in vitro and in vivo

Stroke is one of the major causes of death and disability worldwide. Ischaemic stroke constitutes 80% of stroke incidents. Reperfusion injury following ischaemic stroke has been shown to contribute to major neurological damages. Current conventional treatments for ischaemic stroke, whether surgical or pharmaceutical, focus on restoring cerebral blood flow and preventing expansion of ischaemic damage, but have limited impact on neuron damage or restoring damaged neurological functionalities. Nao Xin Qing (NXQ), a standardised, patented herbal extract derived from Diospyros kaki L., offers potential therapeutic for apoplexy syndrome, including ischaemic stroke. However, NXQ’s effects on ischaemic stroke are unclear. In particular, the mechanisms underlying NXQ’s effects and the key active components responsible for these effects, are not fully understood. This study aims to determine the effects of NXQ and its role in the treatment of ischaemic stroke. The study comprised of two parts. First part to determine the effects of NXQ for ischaemic stroke by evaluating its vascular protective effects and angiogenic effects. This study further identifies the chemical profiles of the NXQ extract and determines which compound/s are responsible for the therapeutic functions for ischaemic stroke. The second part of the study aimed to evaluate the clinical effects of NXQ on ischaemic stroke patients. A study protocol for a randomised, double-blind, placebo-controlled trial was developed to facilitate future studies on the clinical efficacy and safety profile of NXQ for ischaemic stroke patients. NXQ possesses vascular protective effects against H2O2-induced damage that may protect endothelial cells from reperfusion-induced damage. Additionally, NXQ possesses potential angiogenesis and revascularisation properties, which may contribute to its therapeutic action during ischaemic stroke recovery

Characterization and Clinical Management of Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a particular phenotype of non-ischemic systolic heart failure, frequently recognizing a genetic background and affecting relatively young patients with few comorbidities. Nowadays, long-term survival of DCM patients has been markedly improved due to an early diagnosis and uninterrupted and tailored follow-up under constant optimal medical and non-pharmacological evidence-based treatments. Nevertheless, DCM is still one of the most common causes of heart transplantation in the western world. Clinical management requires an integrated and systematic use of diagnostic tools and a deeper investigation of the basic mechanisms underlying the disease. However, several emerging issues remain debated. Specifically, the genotype–phenotype correlation, the role of advanced imaging techniques and genetic testing, the lack of appropriate risk stratification models, the need for a multiparametric and multidisciplinary approach for device implantation, and a continuous reclassification of the disease during follow-up remain challenging issues in clinical practice. Therefore, the aim of this Special Issue is to shed the light on the most recent advancements in characterization and clinical management of DCM in order to unveil the conundrum of this particular disease

An analysis of the immune and vascular systems in untreated hypertension

Background: Blood pressure regulation leads to hypertension through complex environmental and genetic interactions, mediated by cardiac, vascular, endocrine, and renal systems. The immune system interacts with all of these, and may have a role in hypertension and associated organ damage. Methods and Results: The Inflammatension study comprehensively assessed vascular function (endothelial function, arterial stiffness, intima-media thickness, and cardiovascular variability), the immune cell ‘signature’ (including B and T cell subsets, monocyte and dendritic cells, and intracellular stimulation studies), and circulating protein biomarkers, in an untreated hypertensive group compared to normotensive controls, and in consideration of phenotypic groups, as follows. Does cardiovascular function differ between incident hypertension versus healthy controls? Hypertensive disease progression involves early arterial stiffness. Carotid atherosclerosis and impairment in endothelial function were not detected. Measures of arterial stiffness strongly correlate with each other, with ambulatory and central BP, and with cardiovascular variability. Are phenotypic subgroups apparent in hypertension? White coat hypertension patients demonstrated arterial stiffening in excess of sustained hypertension; masked hypertension patients vascular characteristics were akin to normotension. Machine learning techniques generated three phenotypic groups of hypertension, ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’. Identifying immune cell ‘signature’ in patients: Flow cytometry demonstrated lower CD4+ naïve cells (CD45RA+CCR7+CD45RO+CD62L+) in hypertension. CD4+ T central memory cells were expanded in hypertension, along with CD62- T effector memory cells in an adjusted model. Hypertensive group had proportionally fewer CD28+ lymphocytes and CD8+ TEMRA cells, and T cells polarised towards Th1/Tc1 and Th17.1/Tc17.1. Intermediate monocytes demonstrated a differing pattern of CCR2 and CCR5 chemokine receptor expression, and alterations in STAT1 and STAT6 phosphorylation cascades. Increased NK cell CD56+Dim expression and reduced NKT and T lymphocytes CD122 expression was linked to hypertension. Nocturnal non-dipping was associated with similar immune cell signature changes as hypertension, and dendritic cell mannose receptor downregulation in addition. The circulating protein biomarker ‘signature’ of untreated hypertension and hypertensive phenotypes: Cytokines and chemokines dominated the 34 biomarkers differing between normotension and hypertension, though failed to meet Bonferroni-adjusted thresholds. Inflammatory biomarkers correlated with BP and arterial stiffness, but not endothelial function. Associations were concordant across systolic and diastolic BP; TPP1, CCL7, CCL11, and CCL21 positively correlating; IL18R1, and KYNU negatively. These relationships were more pronounced in the hypertensive subgroup, especially CD molecules and cytokines. HGF, AGE, and CCL21 showed greatest between-group differences and correlations across arterial parameters. Systolic nocturnal dipping demonstrated negative correlation with immune cell interaction and cellular adhesion biomarkers (CTRC, EPHA1, LGALS4, SIT1, SMOC, IL-18 and TNFSF11). Sixteen of the 85 correlating biomarkers also differed between the ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’ phenotypic groups. Conclusions: In untreated hypertension arterial stiffness is already detectable, and along with nocturnal dipping and estimates of central BP, categorise hypertensive phenotypes. The exploratory data support alterations of circulating immune biomarkers, and innate (monocytes) and adaptive (T cells) immune compartments. Nocturnal dipping and hypertension phenotypes especially demonstrate immune system variances

The role of donor CD4 T lymphocyte chimerism in lung transplant recipients

Abstract Long-term outcomes for lung transplantation remain disappointing; as many as 50% of lung transplant recipients develop progressive Bronchiolitis Obliterans Syndrome (BOS) by 5 years after transplant. In the last decade, several experimental and clinical studies have demonstrated that cellular and humoral autoimmune responses to ‘self’ antigens may play a causative role in the onset of BOS. Work from our research group has highlighted a novel mechanism for triggering autoimmunity following transplantation. In a murine model of chronic heart rejection, transplant-induced autoimmunity - characterised by production of class-switched anti-nuclear effector autoantibody responses was dependent upon provision of help from donor CD4 T cells that were passengers within the graft. However, the fate of the donor passenger CD4 T cells in clinical organ transplantation is unclear. To assess whether a similar mechanism may occur in human transplant recipients, I have studied the presence and the impact of passenger donor CD4 T cells on the development of humoral auto- and alloimmune responses in a prospective cohort of primary lung transplant recipients (n=21). The development of autoantibody and, in particular, the specificity of target autoantigens was also evaluated in a lung transplant patients with either established grade 2-3 BOS (n=10), or without BOS (n=10). My work suggests that the presence of donor CD4 T cell chimerism in the peripheral blood of lung transplant recipients is a uniform phenomenon. Donor CD4 T lymphocytes were consistently detected in the recipients’ peripheral blood during the first post-operative month; however, the number of detectable donor CD4 T cells fluctuated over time, and varied between individual lung transplant recipients. In a follow-up period of one year after transplantation, three distinct patterns of donor CD4 T cell chimerism were observed: short (donor CD4 T cells detectable for up to six weeks after transplantation, n=13), intermediate (donor CD4 T cells detectable between three to six months after transplantation, n=3) and long-lasting chimerism (donor CD4 T cells detectable for more than six months after transplantation, n=5). Surprisingly, the degree of HLA mismatching and the predicted NK cell alloreactivity did not correlate with the longevity of donor CD4 T cell chimerism, and did not influence the development of BOS. Furthermore, transcriptomic analysis of the donor CD4 T cell population consisted of a heterogenous mixture of different CD4 T cell sub-types, with no consistent pattern evident in patients with short and long lasting donor CD4 T cell chimerism. The assessment of the humoral autoimmune responses revealed unexpected findings. Anti-nuclear IgG autoantibody levels were greater in the recipients’ sera before the transplant, when compared to sera sampled at one and 12 months after transplantation, but the titre of pre-transplant anti-nuclear autoantibody did not correlate with the subsequent development of BOS. Similar findings were observed in the retrospective cohort of 24 lung and 18 heart and lung transplant recipients. Assessment of the repertoire of pretransplant autoantibody did however suggest that a unique set of autoantigens were targeted in those patients that subsequently developed BOS. The involvement of donor CD4 T cell in the development of transplant-induced autoimmunity and augmentation of humoral alloimmunity was not confirmed in human lung transplant recipients and the role of donor CD4 T chimerism remains unclear. However, solid organ transplant recipients are subjected to highly potent T-cell depleting immunosuppressive drugs that can alter the number and function of T cells. This may obviate the impact of donor CD4 T cell chimerism in the development of transplant-induced autoimmunity. Understanding the clinical relevance of the autoantibody repertoire present at the time of transplant may, however, hold potential in identifying recipients with predisposition to develop BOS, and may therefore possibly provide a window of opportunity for targeted immunosuppression.This thesis was supported by The British Heart Foundation, Non-Clinical PhD Studentship Grant (RG088); Papworth Hospital research grant (to Dr Jasvir Papmar) and Addenbrooke’s Charitable Trust (to Mr Gavin J. Pettigrew)

BESAFE - ASIAN PACIFIC ISLANDER MODEL BOOK

Softback cultural competency book detailing the BESAFE model for Asian Pacific Islander Americans, 6.75 inches by 9.5 inches.https://dh.howard.edu/nmaetc_pubs/1003/thumbnail.jp