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Background: Typical voluntary bolus swallowing consists of a single discrete oropharyngeal swallow. Multiple Swallow Behaviour, such as piecemeal deglutition, is also known to occur in health. We h...

Diffuse large B-cell lymphoma (DLBCL) is the most common form of Non-Hodgkin Lymphoma (NHL) in adults. Affecting nearly 7 out of every 100,000 people in the United States annually, this hematogenous neoplasm is known for its aggressiveness and rapid development. Being the most common NHL, it has been divided into several subgroups based on pathogenesis and treatment methods. In particular, subtypes such as germinal center, activated B-cell-like, and primary mediastinal diffuse large B-cell lymphomas have been divided by their uniqueness of pathology at the cellular level. Knowing the numerous cytokines, inflammatory markers, and other microcellular processes that these lymphomas disrupt can help target an effective therapeutic at the disease.

There is currently no system to track the emergence of Zika virus (ZIKV) subtypes. We developed a surveillance system able to retrieve sequence submissions and further classify distinct ZIKV genotypes in the world. This approach was able to detect a new occurrence of ZIKV from an African lineage in Brazil in 2019.

Background Serotyping of Streptococcus pneumoniae is important for monitoring of vaccine impact. Unfortunately, conventional and molecular serotyping is expensive and technically demanding. This study aimed to determine the ability of matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) mass spectrometry to discriminate between pneumococcal serotypes and genotypes (defined by global pneumococcal sequence cluster, GPSC). In this study, MALDI-TOF mass spectra were generated for a diverse panel of whole genome sequenced pneumococcal isolates using the bioMerieux VITEK MS in clinical diagnostic (IVD) mode. Discriminatory mass peaks were identified and hierarchical clustering was performed to visually assess discriminatory ability. Random forest and classification and regression tree (CART) algorithms were used to formally determine how well serotypes and genotypes were identified by MALDI-TOF mass spectrum. Results One hundred and ninety-nine pneumococci, comprising 16 serotypes and non-typeable isolates from 46 GPSC, were analysed. In the primary experiment, hierarchical clustering revealed poor congruence between MALDI-TOF mass spectrum and serotype. The correct serotype was identified from MALDI-TOF mass spectrum in just 14.6% (random forest) or 35.4% (CART) of 130 isolates. Restricting the dataset to the nine dominant GPSC (61 isolates / 13 serotypes), discriminatory ability improved slightly: the correct serotype was identified in 21.3% (random forest) and 41.0% (CART). Finally, analysis of 69 isolates of three dominant serotype-genotype pairs (6B-GPSC1, 19F-GPSC23, 23F-GPSC624) resulted in the correct serotype identification in 81.1% (random forest) and 94.2% (CART) of isolates. Conclusions This work suggests that MALDI-TOF is not a useful technique for determination of pneumococcal serotype. MALDI-TOF mass spectra appear more associated with isolate genotype, which may still have utility for future pneumococcal surveillance activities.

Key words:immunoglobulin, coombs test, hemolysis, HIV, quantification Introduction A positive direct antiglobulin test (DAT, Coombs test) is valuable in identifying the etiology of autoimmune hemolysis and in guiding an immunomodulatory therapeutic intervention strategy. However, in HIV positive individuals with background polyclonal gammopathy, a false positive DAT is common. In this setting, immunoglobulin quantification and subtyping may be of value in characterizing the autoimmune hemolysis. There is paucity of published literature evaluating the diagnostic usefulness of IgG subtyping and quantification in HIV positive individuals who are investigated for possible autoimmune haemolysis (AIHA). The recently introduced gel card used for AIHA diagnosis can subtype and quantify the IgG antibody titre. This study evaluated the usefulness of IgG quantification and subtyping in the diagnostic workup of autoimmune hemolysis in patients who were DAT positive with and without HIV infection. Methods: This retrospective, cross sectional study was reviewed and approved by the institutional Ethics Committee. The study population included HIV positive and HIV negative patients who were investigated for autoimmune hemolysis in a quaternary care hospital as part of their diagnostic workup. Those with a positive DAT had their IgG subtyped and quantified using the ID -Card DAT IgG1/IgG3 and IgG-dilution cards (Bio-Rad©, Cressier, Switzerland). Results: From December 2019 to March 2020, 90 patients admitted in our hospital were investigated for AIHA. Forty four (49%) were found to be DAT positive. Of those who were DAT positive, 26 (59%) had biochemical evidence of haemolysis (raised LDH, raised unconjugated bilirubin). Of the total DAT positive population, 16 (36%) were HIV positive. Concurrent HIV and haemolysis was present in 8 patients. Four of the 8 had antibody titre≤1:30. Most patients had IgG 1 subtype. None of the HIV positive patients without features of haemolysis had IgG1 or IgG3 subtypes present and 2 of the 8 had antibody titres≤1:30. Conclusion: IgG quantification and subtyping was found to be of limited value in the diagnostic characterization of AIHA in HIV positive patients with false positive DAT. Disclosures Mahlangu: CSL Behring, Catalyst Biosciences, Freeline Therapeutics, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda:Consultancy;CSL Behring, Catalyst Biosciences, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda:Speakers Bureau;South Africa Medical Research Council, Wits Health Consortium, Colleges of Medicine of South Africa:Membership on an entity's Board of Directors or advisory committees;BioMarin, CSL Behring, Freeline Therapeutics, Novo Nordisk, Novartis, Pfizer, Sanofi, F. Hoffmann-La Roche Ltd, uniQure:Research Funding.

peer-reviewed Phenotypic, chemotaxonomic and genotypic data from 12 strains of Escherichia coli were collected, including carbon source utilisation profiles, ribotypes, sequencing data of the 16S–23S rRNA internal transcribed region (ITS) and Fourier transform-infrared (FT-IR) spectroscopic profiles. The objectives were to compare several identification systems for E. coli and to develop and test a polyphasic taxonomic approach using the four methodologies combined for the sub-typing of O157 and non-O157 E. coli. The nucleotide sequences of the 16S–23S rRNA ITS regions were amplified by polymerase chain reaction (PCR), sequenced and compared with reference data available at the GenBank database using the Basic Local Alignment Search Tool (BLAST) . Additional information comprising the utilisation of carbon sources, riboprint profiles and FT-IR spectra was also collected. The capacity of the methods for the identification and typing of E. coli to species and subspecies levels was evaluated. Data were transformed and integrated to present polyphasic hierarchical clusters and relationships. The study reports the use of an integrated scheme comprising phenotypic, chemotaxonomic and genotypic information (carbon source profile, sequencing of the 16S–23S rRNA ITS, ribotyping and FT-IR spectroscopy) for a more precise characterisation and identification of E. coli. The results showed that identification of E. coli strains by each individual method was limited mainly by the extension and quality of reference databases. On the contrary, the polyphasic approach, whereby heterogeneous taxonomic data were combined and weighted, improved the identification results, gave more consistency to the final clustering and provided additional information on the taxonomic structure and phenotypic behaviour of strains, as shown by the close clustering of strains with similar stress resistance patterns. The authors acknowledge the financial contribution of the Spanish INIA, the Research Council of Norway (project 178230/I10), Foundation for Levy on Foods, the Norwegian Research Fees Fund for Agricultural Goods, the Norwegian Independent Meat and Poultry Association, Nortura SA and NHO Matog Landbruk.

It has long been understood that stratification of patients into fine-grained cohorts is a foundation of accurate diagnosis and effective treatment of complex diseases, such as cancer. Nevertheless, cancer therapies still fail or cause unnecessary suffering to many patients, which suggests that our current understanding of cancer sub-types needs to be refined. In this paper, we propose CLIGEN, a novel computational pipeline for high-throughput data-driven stratification of patients with a complex disease into cohorts corresponding to multi-modal disease sub-types based on clinical and genomic data. We applied CLIGEN to discover breast cancer sub-types based on the clinical and genomic data of 503 patients with breast ductal carcinoma in the Cancer Genome Atlas (TCGA). Quantitative and qualitative evaluation of the breast cancer sub-types discovered by CLIGEN indicate that they are biologically meaningful and correlate with clinical outcomes, such as patient survival time.

Molecular stratification of cancer patients is driving the development of precision medicine-targeted therapies. Clustering of tumor samples based on gene expression profiles from high-throughput platforms, such as microarrays or NextGen sequencing, has resulted in distinct tumor subtypes for numerous cancers. However, the majority of the derived classifiers or gene signatures have not reached clinical utility. Therefore, informatics methods to accurately translate the derived gene-signature from the high-throughput platform to a clinically adaptable low-dimensional platform are critical. In this chapter, we discuss a workflow to derive and then transfer gene signatures from one analytical platform to another for cancer patient stratification. We summarize the results of the workflow on two different cancers. Finally we discuss the importance of data-discretization in dealing with the cross-platform data and incorporating the splice-variant or isoform-level gene expression profiles in the statistical analyses.

Background: Nigeria suffered waves of Highly Pathog enic Avian Influenza (HPAI) outbreaks that peaked twice in February 2006 and February 2007. The outbr eaks affected 3,057 commercial and rural household farms causing 1.3 million of the country’ s poultry destroyed. The burden of Influenza is likely to be under estimated and because of the uns table nature of the virus it call for the mapping o f this virus to specific region, this study therefore seeks to identify the types, prevalence, strain, predilection of the organism so as to monitor the o ccurrence of influenza in this part of the country with the aim of providing a base line level of intervent ion of influenza virus and find the candidate virus for vaccine selection and production. This study is a c ross sectional survey, our target populations were all pediatric and adult patients admitted at the pe diatrics and internal medicine department of ATBUTH who has met the criteria for presence of cough, fev er (>37 o C), nasal congestion and dyspnoea. Samples were collected and analyzed using the polym erase chain reaction (PCR), for the presence and sub typing of influenza viruses in respiratory spec imens. Overall 5% of the samples collected tested positive for human influenza type A and B. During a verage epidemics, overall attack rates are estimate d to be 10–20%, but in certain susceptible population s such as schoolchildren or nursing home residents, attack rates of 40–50% may occur. 60% of the positi ve results were among the female samples where as 40% from the male samples

We developed and validated an allele-specific PCR method for detecting the nine main Escherichia coli phylogroup B2 lineages involved in extra-intestinal infections, which could be used as a substitute for multilocus sequence typing in studies for which the greater resolution at the sequence type level is not needed.

Members of the genus Pectinatus (P.) are feared contaminants in the brewing industry as their growth in beer results in the production of metabolites, which cause serious off-flavors such as hydrogen sulfide. Thus, identification and differentiation of the species P. cerevisiiphilus, P. frisingensis and P. haikarae is of vital interest. Nineteen isolates of Pectinatus were analyzed by matrix-assisted-laser desorption–ionization time-of-flight mass spectrometry (MALDI-TOF MS). Reference spectra were recorded for four isolates representing the three species P. cerevisiiphilus, P. frisingensis and P. haikarae, which enabled reliable identification of the remaining fifteen isolates as P. frisingensis. All isolates were further examined to investigate MALDI-TOF MS’s potential to differentiate between various isolates of Pectinatus species. Upon generation of reference database spectra, sixteen out of nineteen isolates could be distinguished based on differences in their MALDI-TOF MS fingerprint. Two out of three misidentifications occurred between highly similar isolates originating from the same brewery. As MALDI-TOF MS spectra were reliably assigned to the corresponding isolate in more than 80 % of all cases, the application of MALDI-TOF MS could help to track contaminants in the production system and to monitor efforts to eliminate them.

As a vast majority of the human listeriosis cases are caused by serotypes 1/2a, 1/2b and 4b strains, it is imperative that strains from clinical as well as from food and environment are further characterised so that accurate and timely epidemiological determination of sources of the contamination can be established to minimise the disease burden. Recent developments in the field of genomics provide a great opportunity to use these tools towards the development of molecular sub-typing techniques with a greater degree of discrimination spanning the entire length of the genome. This brief review summarises a few of these DNA-based techniques with an emphasis on DNA microarray and other whole genome sequencing-based approaches and their usefulness in Listeria monocytogenes sub-typing and outbreak investigations.

Despite the increasing recognition of noroviruses as major pathogens associated with community-acquired diarrhoea in children, there are few studies from Africa. Long-term surveillance studies of rotavirus gastroenteritis in Malawian children have provided an opportunity to undertake a study of the importance and epidemiological features of norovirus infection in this population. Faecal specimens were collected from children

Objective: To assess whether psychiatrists in the community operate to a sub-typing model of mood disorders when choosing psychotropic medications. Method: Patients assessed through the Black Dog Institute depression clinic provided information on their previously prescribed and current medications, on how effective they found them and whether they had to be ceased due to side-effects. The prevalence of each medication trialled was analysed according to diagnosis (bipolar I, bipolar II, unipolar melancholic depression or unipolar non-melancholic depression). Results: Analyses indicate that psychiatrists prescribe medications differentially in line with diagnosis. This effect was found in both previously prescribed and currently prescribed medications, and was most distinct for mood stabiliser and antipsychotic medications. Several medications, in contrast, appeared to have been trialled by the majority of patients, regardless of diagnosis. Analyses of effectiveness and cessation due to side-effects were compromised by small sub-sample sizes. Conclusions: Psychiatrists in the community appear to operate to a sub-typing model of mood disorders, preferentially prescribing many medications according to mood disorder sub-type.

Research Objective: The focal objective in this study is to investigate the user generated counter-stereotypic responses against 'The Innocence of Muslims" film in terms of taking actions in their responses videos. Research sample: Content analyses of 400 video clips were conducted in terms of forms and contents. Theory: This study is theorized in the light of social presence theory and counter-stereotypic model. Results: - indicated that Multiplication of views were facilitated, instead of exchanging views or engaging in rich dialogue. Counter stereotypic vision were effectively and spontaneously employed in the form of "Dawah" calling for Islam. Western Muslims more likely tended tocounter stereotyping Islam and consciously engaging in fruitful dialogues. Finally, there was a lack of depth in terms of addressing the sophisticated frames which manipulate the negative stereotyping of Islam. - There Is a Significant Relationship between Using Exemplification as a Counter-Stereotypic Model And attracting High Number of Positive Text Comments with a High Positive Tunes". - "There Is A Significant Relationship Between Using Sub Typing As Counter-Stereotypic Model And Attracting High Number Of Negative Text Comments".

Activity logs involve patients writing down their activities and symptoms over 1 or more days. Aims This study sought to classify daily fatigue patterns among patients with chronic fatigue syndrome (CFS) using activity logs.Fatigue intensity was self-reported every 30 min in a sample of 90 patients with CFS over 1 day. A cluster analysis using fatigue intensity, variability and slope was conducted.Three clusters emerged involving patients with different trajectories. One group evidenced high fatigue intensity, low variability, and fatigue intensity stayed the same over time. A second group had moderate fatigue intensity, high variability, and fatigue intensity decreased over time. A third group had moderate fatigue intensity, high variability, but fatigue intensity increased over time. The three clusters of patients differed on measures of actigraphy, pain and immune functioning.Activity logs can provide investigators and clinicians with valuable sources of data for understanding patterns of fatigue and activity among patients with CFS.

We are at the cusp of significant new alternatives for the treatment of chronic hepatitis C. Among more than 100 drugs in development, some are ready to be approved and in the market as soon as next year. The protease inhibitors Telaprevir and Boceprevir, will change the SOC treatment to triple therapy, (combined with peg IFN and RBV), with duration of treatment guided by rapid virological response. In this article we present the data supporting the approval of Telaprevir and Boceprevir, and information on polymerase inhibitors and IFN free proof of concept trials. Finally we discuss which patients should wait for DAA based therapies and which should be considered for peg IFN/RBV now. In the next 5 years our patients can expect higher response rates and truncated duration of therapy. They can expect drug cocktails or combos but for the next years these novel drugs will still require peg IFN and RBV. Also, a new era of resistance as a barrier to therapy will require sub typing and more viral monitoring. Overall, improved outcomes will come at the expense of more adverse events and increased costs of treatment.

Subtyping in first order object calculi is studied with respect to the logical semantics obtained by identifying terms that satisfy the same set of predicates, as formalised through an assignment system. It is shown that equality in the full first order ς-calculus is modelled by this notion, which in turn is included in a Morris-style contextual equivalence.

The coal petrologist looks to focus the petrographic attributes of natural and inorganic coal constituents and their parallel and vertical varieties inside of a solitary coal sample of a specific coal field. Conventional investigation of coal by a petrologists are subjected to diverse insufficiencies like inter and intra observation throughout screen analysis and various machine usage, slowness, need of experienced petrologists and tiredness. In chemical examination, usage of conventional analyzers is unrestrained for characterization technique. In this paper, image analysis serves as an incredible computerized characterization procedure of subtyping the coal, according to their textural, and color features. Coal characterization is imperative for the right use of coal in the power and steel industries etc. Henceforth, in this paper, endeavors are made to devise a methodology for an automated characterization and sub typing of different grades of coal samples using image processing and standard neural network techniques.

Proposed by W3C (World Wide Web Consortium), XQuery is a descriptive query language for XML structured data or documents. The specification of XQuery gives functional description of XQuery’s typing system, but doestn’t provide methods to judge the Sub-typing and inDOM relations in language compiling. In this paper, both of the two important relations: Sub-typing and inDOM, are described and analyzed. After some definitions of Tree Automaton, the judgment algorithms of these two relations are proposed.

The epidemiological investigation of Escherichia coli O157 is complicated by the lack of heterogeneity between strains responsible for the majority of cases of infection. As a consequence it is difficult to reliably cluster together an outbreak strain and differentiate it from other sporadically occurring isolates. The methods available for the sub-typing of E. coli O157 vary in their speed, technical complexity, cost and ability to discriminate reliably between strains, with many of the recently developed methods targeting the genome to provide differentiation. No single typing method is individually superior, and ideally a combination of techniques should be employed depending on the level of discrimination required and time or resources available. The aim of this review is to consider the relative merits of the available typing methodologies with particular emphasis on those which may find application in a diagnostic laboratory.

International audience; The fusion calculi are a simplification of the pi-calculus in which input and output are symmetric and restriction is the only binder. We highlight a major difference between these calculi and the pi-calculus from the point of view of types, proving some impossibility results for subtyping in fusion calculi. We propose a modification of fusion calculi in which the name equivalences produced by fusions are replaced by name preorders, and with a distinction between positive and negative occurrences of names. The resulting calculus allows us to import subtype systems, and related results, from the pi-calculus. We examine the consequences of the modification on behavioural equivalence (e.g., context-free characterisations of barbed congruence) and expressiveness (e.g., full abstraction of the embedding of the asynchronous pi-calculus).

Out of the several molecular methods currently available, pulsed field gel electrophoresis (PFGE) is one of the most discriminatory and reproducible methods for the sub-typing of Listeria monocytogenes (L. monocytogenes) (Kerouanton et al., 1998; Brosch et al., 1996). The combination of restriction endonucleases AscI and ApaI has shown excellent discrimination for L. monocytogenes (Brosch et al., 1996). Thus, the PFGE method, using these two enzymes, is considered to be the international standard for sub-typing (Graves and Swamminathan, 2001). However, although the protocol has been shortened to 30 hours from the time a pure culture of the bacteria has been obtained (Graves and Swamminathan, 2001), PFGE remains a manual, time-consuming and labor intensive subtyping method. It also requires highly skilled operators and does not offer standardized reagents.

Gallibacterium anatis has been suggested to have a causal role in the salpingitis/peritonitis complex in chickens, beside its isolation from the respiratory tract. As G. anatis strains from different flocks were compared by MALDI-TOF MS proteomic phenotyping it could be demonstrated that in most flocks one clonal lineage was present. This finding is also reflected by data achieved when isolates from different organs within a bird generally belong to the same clonal lineage. In addition, it was also confirmed by two independent experiments, as well as, two MALDI instruments. Altogether, proteomic phenotyping indicates that the nature of a chicken flock may play a certain role in particular clone type selection of G. anatis.

Background: The future of personalized medicine depends on advanced diagnostic tools to characterize responders and non-responders to treatment. Systems diagnosis is a new approach which aims to capture a large amount of symptom information from patients to characterize relevant sub-groups. Methodology: 49 patients with a rheumatic disease were characterized using a systems diagnosis questionnaire containing 106 questions based on Chinese and Western medicine symptoms. Categorical principal component analysis (CATPCA) was used to discover differences in symptom patterns between the patients. Two Chinese medicine experts where subsequently asked to rank the Cold and Heat status of all the patients based on the questionnaires. These rankings were used to study the Cold and Heat symptoms used by these practitioners. Findings: The CATPCA analysis results in three dimensions. The first dimension is a general factor (40.2% explained variance). In the second dimension (12.5% explained variance) 'anxious', 'worrying', 'uneasy feeling' and 'distressed' were interpreted as the Internal disease stage, and 'aggravate in wind', 'fear of wind' and 'aversion to cold' as the External disease stage. In the third dimension (10.4% explained variance) 'panting s', 'superficial breathing', 'shortness of breath s', 'shortness of breath f' and 'aversion to cold' were interpreted as Cold and 'restless', 'nervous', 'warm feeling', 'dry mouth s' and 'thirst' as Heat related. 'Aversion to cold', 'fear of wind' and 'pain aggravates with cold' are most related to the experts Cold rankings and 'aversion to heat', 'fullness of chest' and 'dry mouth' to the Heat rankings. Conclusions: This study shows that the presented systems diagnosis questionnaire is able to identify groups of symptoms that are relevant for sub-typing patients with a rheumatic disease. © 2011 van Wietmarschen et al.

BackgroundAdult renal epithelial neoplasms are a heterogeneous group with varying prognosis and outcome requiring sub-classification.MethodsCases of renal cell carcinoma (RCC) in a 10 years period were analyzed with regard to the clinical features and histology. Sections were reviewed by four pathologists and the discordant cases were resolved with the help of Hale's colloidal iron stain, vimentin, CK 7, and vinculin immunostains and electron microscopy.ResultsAmongst the total of 278 cases, clear cell renal cell carcinoma was the commonest tumor with 74.8% cases, followed by papillary RCC 12.2%, chromophobe RCC 7.9%, oncocytoma 1.8%, and one case of collecting duct RCC. Eight cases were of sarcomatoid renal cell carcinoma. In 28/278 cases, diagnoses varied amongst the four pathologists and the discordance was resolved by Hale's colloidal iron stain, CK7 immunostain and electron microscopy. Vimentin and vinculin did not contribute much in differentiating subtypes of renal cell carcinomas. Relative incidence of sub-types of RCCs was compared with other seriesConclusionTo accurately subclassify renal cell carcinomas, simple ancillary techniques would possibly resolve all difficult cases. The relative incidence of sub-types of renal cell carcinoma is relatively consistent the world over. However, in India, RCCs afflict the patients two decades earlier.

INTRODUCTION:Pattern of leukemia is known to vary widely throughout the world. The characterization of distribution patterns of different subtypes of leukemia in Nepal needs further study. We wanted to study the leukemia pattern in our institute.METHODS:A retrospective study of 196 cases of leukemia, diagnosed at BPKIHS, between January 1997 to December 2002 was done. We analyzed the pattern of leukemia at BPKIHS by morphological subtype, gender, age at diagnosis, time period of diagnosis (seasonality), and geographic distribution.RESULTS:Morphological sub typing showed that 121 cases were of acute leukemia and 75 of chronic leukemia. Chronic myeloid leukemia constituted the single largest group comprising 35.2 % of all cases, followed by acute myeloid leukemia (28.57 %) and acute lymphoid leukemia (19.9 %). Maximum numbers of cases were from the lowlands while least number of cases were from the mountain districts. Results were compared with literature from Nepal and other countries. This is the second series of leukemia from Nepal.CONCLUSIONS:The data published in this study reflects the leukemia pattern in the eastern region of Nepal. The pattern and distribution of AML, CML, ALL was similar to that in the developed western countries while the lesser frequency of CLL was similar to that in Southeast Asian regionKey Words:leukemia, pattern, eastern Nepal, seasonality.

Background: Fine Needle Aspiration Cytology (FNAC) is a useful, safe and cost effective tool that is used in the diagnosis of lesions in various organs. Even though the literature on FNAC of soft tissue masses is relatively scarce, a large amount of interest has developed in this area in the last few years due to the low cost of the procedure, low incidence of complications, feasibility and high therapeutic efficiency. So the present study was undertaken to study the nature of various soft tissue tumors by FNAC and to compare the cytological diagnosis with the results obtained by biopsy. Methods: All cases 713 (Prospective-217 and Retrospective 496) included in present series were taken up for study. Aspiration of soft tissue lesions were performed following the technique of Zajicek et al. Smear was prepared, stained and examined. Histopathological details were available in 140 cases. Data was compiled in MS excel and checked for its completeness, correctness and then it was analyzed. Results: Total number of 11,560 FNAC was done in six and half year’s period from 1 st April 2003 to 30 th September 2009. Out of the total 713 cases of soft tissue tumors, 71.25% were reported as benign and 28.75% as malignant. Soft tissue tumors were more common in males in comparison to females, with M: F-1.63:1. Accuracy of FNAC for benign and malignant soft tissue tumours was 88.1% and 92.9% respectively. Conclusion: The overall diagnostic accuracy of FNAC in the present study was found 90%. FNAC is a safe and reliable method of recognizing benign and malignant soft tissue tumors and in most instances histological sub typing is possible. Cytological diagnosis must be based on strict cytological criteria and well controlled ancillary techniques.

Peptides binding to HLA molecules elicit specific T cell immune responses and are useful in the development of peptide vaccines and therapeutics. Thus, prediction of HLA-binding peptide is critical. Here, a prediction model is described. Many statistical and molecular mechanics models for HLA peptide binding prediction have been developed and tested during the last decade. However, their efficiency and HLA diversity coverage are far from satisfactory. Analysis of structural data revealed that there are polymorphic pockets in the HLA peptide binding groove that can accommodate the anchor residues of the peptide. The residues that form the pocket determine the geometry and chemical properties of these structural pockets and thus determine the antigen peptides that would be preferentially bound. This accounts for the differential ability of different alleles to bind a variety of peptides. Thus, the peptide-binding groove of the HLA is essentially an exchange or shuffling of pockets among different allele. Based on this analysis, a novel predictive model for HLA peptide binding was developed. The model was extensively cross-validated using peptide binding data. This model is superior to many existing methods because of its potential application to any given HLA allele whose sequence is clearly defined. DOCTOR OF PHILOSOPHY (MAE)

Publisher Summary Molecular typing and tracking of pathogens allows investigators to determine the chain of infection/contamination, through detection of the reservoir of the agent of interest, by uncovering the mode of transmission to a susceptible host and through the determination of the means of entry into the host. Additionally, information acquired from molecular typing and tracking of pathogens can (i) facilitate the detection of outbreaks within flocks or herds, (ii) facilitate the detection of emerging isolates with increased virulence properties, (iii) assist in the assessment of the effectiveness of current control measures, (iv) assist in the establishment of risk reduction strategies, and (v) assist in evaluating the effectiveness of food safety programs. There are several parameters to consider when choosing a typing method and this chapter highlights these parameters. In general, the classification and sub typing of organisms can be divided into two categories: phenotypic-based technologies or genotypic-based technologies. Phenotypic methods are based upon the detection of characteristics that are expressed by an organism, whereas genotypic methods are based upon the analysis of nucleic acids and sequence polymorphisms within an organism. The chapter describes these methods.

We examine the proposition that dysfunctional parenting is more likely to be experienced by those with non-melancholic (compared to melancholic) depression and that, as a consequence, such specificity allows the validity of varying definitions of melancholia to be examined and their utility sharpened. We study a sample of 245 non-psychotic patients meeting DSM-III-R criteria for a major depressive episode and assign them to melancholic and non-melancholic sub-sets according to five separate sub-typing measures (DSM-III-R; DSM-IV; Newcastle; 'Clinical' and CORE criteria). We assess dysfunctional parenting by use of the Parental Bonding Instrument (PBI), and by structured psychiatrist assessment and self-report ratings of a range of dysfunctional parental experiences, with independent assessment and self-report ratings of a range of dysfunctional parental experiences, with independent assessment of the last by reports from corroborative witnesses and from the patients' referring therapists. The five sub-typing measures assigned varying percentages of the sample (24-42%) to a 'melancholic' sub-type. When Newcastle Index assignments were examined, there was no evidence that dysfunctional parenting had any specificity to non-melancholic depression. Neither the DSM-III-R nor DSM-IV systems demonstrated specificity in relation to PBI scores, but several interview-assessed dysfunctional parenting characteristics were over-represented in their non-melancholic sub-sets. 'Clinical' definition showed the greatest over-representation of dysfunctional parenting to those assigned as having non-melancholic depression. The CORE measure, a behaviourally weighted measure of psychomotor disturbance, was the next most differentiating. Importantly, those assigned as having non-melancholic depression by all five measures were more likely to be rated by corroborative witnesses as being exposed to anomalous parenting, validating the subjects' self-reports, arguing against results being an artefact of clinician-based assessment, and supporting the specificity of dysfunctional parenting to a depressive sub-type.

1015 Background: Neo-tAnGo was an NCRI UK neoadjuvant breast cancer study testing the addition of gemcitabine to anthracycline and taxane-based treatment and also the sequencing of chemotherapy. In a translational substudy, sequential fresh tissue was analysed for PAM 50 subgroups. Methods: Neo-tAnGo recruited 831 patients. 162 patients were consented for Neo-tAnGo Science, for 3 additional fresh tissue samples to be taken at diagnosis (diag), mid-chemotherapy (CT) and end-CT. Standard methodology was used for PAM 50 subtyping. Results: Fresh tissue samples at diag were received from 123 patients (pts). 45 pts (37%) had 2 additional samples provided (at mid- and end-CT). 57 pts (46%) had 1 additional sample provided (34 at mid-CT, 23 at end-CT). PAM 50 subtyping at diag was as follows: 31 (25%) BASAL; 30 (24%) HER2; 39 (32%) LUM B; 13 (11%) LUM A; 10 (8%) NORMAL-like. Pathological complete response rates (pCR: no disease in breast or axillary nodes, n = 121 pts) differed between PAM 50 subtype at diag (p = 0.04): BASAL 11/31 (35%); HER2 8/30 (27%); LUM B 3/37 (8%); LUM A 1/13 (8%); NORMAL-like 3/10 (30%). Of the 94 pts who were not PAM50 NORMAL-like at diag and had 2+ samples, 42 (45%) ‘shifted to NORMAL-like’. This was associated with slightly higher pCR rates (24% vs 15% who didn’t ‘shift to NORMAL-like’, p = 0.44) and borderline significantly higher rates of pCR or minimal residual disease (MRD

Reports of salmonellosis in Northern Ireland exceeded those of campylobacter infections until 1990 but subsequently there has been a marked increase in campylobacter infections and Campylobacter spp. are now the major cause of food-borne infections in the province.1 Since meats are often implicated in cases of campylobacter food-poisoning a survey of raw meats, both at the abattoir and in retail outlets, for the presence of campylobacters was undertaken. In conjunction with the meat survey two genetic methods of subtyping campylobacters, random amplified polymorphic DNA (RAPD) method8,9 and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based on the method of Nachamkin et al (1993), were evaluated to see if they could provide appropriate tools for sub-typing any isolates obtained during the survey. Conventional phenotyping and Penner serotyping was also conducted for comparative purposes. The aim was to find the best method for comparing sub-types and hence determining if the isolates were of a sporadic nature, or from a common source.

Reported cases of food poisoning in Northern Ireland (NI) virtually doubled between 1989 and 1993 and over the same period Campylobacter spp. became the principal cause of gastro-enteritis, replacing Salmonella 1. However whilst typing methods for Salmonella are well developed, and readily available as an epidemiological tool, this situation has yet to arise for the typing of campylobacters. Thus whilst campylobacteriosis is considered to be a food-borne infection mainly caused by products of animal origin, it is difficult to define which sources are predominantly responsible for human infection.

A multi-centre collaborative study was carried out to compare, established sub-typing techniques for C. jejuni based upon phenotypic markers namely serotype, phagetype and biotype with molecular typing methods such as 16S rRNA RFLP’s, pulsed field gel electrophoresis, RAPD, PCR-RFLP and multilocus enzyme electrophoresis, for their relative discriminatory sensitivities and specificities.

In this chapter we study an imperative object calculus with primitive covariant Self types. It is an extension of the first-order calculus of Chapter 11, enriched with the Self types, the variance annotations, and the quantifiers of Chapter 16. A subject reduction result covers sub typing and polymorphism in the presence of side-effects.