What Is Your Diagnosis?

From February 2009 through August 2010, we compared species-level identification of bloodstream Candida isolates and susceptibility to fluconazole, voriconazole, and caspofungin between diagnostic and reference South African laboratories during national surveillance for candidemia. Diagnostic laboratories identified isolates to genus/species level and performed antifungal susceptibility testing, as indicated. At a reference laboratory, viable Candida isolates were identified to species-level using automated systems, biochemical tests, or DNA sequencing; broth dilution susceptibility testing was performed. Categorical agreement (CA) was calculated for susceptibility results of isolates with concordant species identification. Overall, 2172 incident cases were detected, 773 (36%) by surveillance audit. The Vitek 2 YST system (bioMérieux Inc, Marcy l'Etoile, France) was used for identification (360/863, 42%) and susceptibility testing (198/473, 42%) of a large proportion of isolates. For the five most common species (n = 1181), species-level identification was identical in the majority of cases (Candida albicans: 98% (507/517); Candida parapsilosis: 92% (450/488); Candida glabrata: 89% (89/100); Candida tropicalis: 91% (49/54), and Candida krusei: 86% (19/22)). However, diagnostic laboratories were significantly less likely to correctly identify Candida species other than C. albicans versus C. albicans (607/664, 91%vs. 507/517, 98%; P < .001). Susceptibility data were compared for isolates belonging to the five most common species and fluconazole, voriconazole, and caspofungin in 860, 580, and 99 cases, respectively. Diagnostic laboratories significantly under-reported fluconazole resistance in C. parapsilosis (225/393, 57%vs. 239/393, 61%; P < .001) but over-reported fluconazole non-susceptibility in C. albicans (36/362, 10%vs. 3/362, 0.8%; P < .001). Diagnostic laboratories were less likely to correctly identify Candida species other than C. albicans, under-reported fluconazole resistance for C. parapsilosis and over-reported fluconazole resistance for C. albicans.

Background:Significant geographical variations exist in amputation rates and utilization of diagnostic and therapeutic vascular procedures before lower extremity amputations in the United States. The purpose of this study was to evaluate the rates of diagnostic and therapeutic vascular procedures in the year prior to amputation in a contemporary population and correlate with pathological findings of the amputation specimens.Methods:A retrospective analysis was conducted of non-traumatic amputations from 2011 to 2017 at a rural community hospital. We reviewed the proportion of patients undergoing diagnostic (ankle brachial index with duplex ultrasound, computerized tomography angiogram and invasive angiogram) and therapeutic (endovascular and surgical revascularization) vascular procedures in the year prior to amputation. Prevalence of tissue viability and osteomyelitis were evaluated in all amputated specimens and atherosclerotic vascular disease (ASVD) was evaluated in major amputations. We also analyzed primary amputation rates among different subgroups.Results:698 patients were included with 248 (36%) major amputations and 450 (64%) minor amputations. Any diagnostic procedure was performed in 59% of the major amputations and 49% of the minor amputations (P = 0.01). Any therapeutic revascularization procedure was performed in 34% of the major amputations and 28% of the minor amputations (P = 0.08). The pathology of major amputation specimens revealed severe ASVD in 57% and mild-moderate ASVD in 27% of specimens. Tissue viability was significantly higher in major amputations (90% vs 30%, P = 0.04) and osteomyelitis was significantly higher in minor amputations (50% vs 14%, P = 0.03). Primary amputations were performed in 66% of major amputations, 72% of minor amputations, 81% with mild to moderate ASVD and 54% with severe ASVD.Conclusion:Diagnostic and therapeutic vascular procedures appear under-utilized for patients undergoing lower extremity amputations at a rural community hospital. ASVD rates and tissue viability imply that revascularization could be of significant benefit to avoid major amputation.

Background: Circulating tumor DNA (ctDNA) is now widely used across a variety of malignancies as a viable “liquid biopsy” method, with applications in early detection, treatment response evaluation, prognostication, and recurrence monitoring. Recently, ctDNA derived from the tumor-integrated HPV (ctHPVDNA) has borne promising results in HPV-associated cancers, including HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Studies indicate that undetectable ctHPVDNA after complete surgical excision in HPV+ OPSCC corresponds with improved prognosis. However, ctHPVDNA kinetics after diagnostic procedures such as transoral robotic surgery (TORS) in head neck squamous cell carcinoma from an unknown primary (HNSCCUP) or unknown primary has not been extensively studied. The purpose of this study is to show an unexpected trend in NavDx levels following these procedures. Methods: Patients undergoing TORS at Stanford University (September 2023 and August 2024) were prospectively screened and enrolled. A commercially available ctHPVDNA assay (NavDx) was collected at baseline, immediate postoperative (24-48 hours), 7-14 days following surgery, 3 months post- treatment and every 3 months thereafter up to 12 months. Results: Eight patients presented with HNSCCUP, 87.5% (7/8) had detectable baseline ctHPVDNA levels ranging from 2 to 1237. 75% (6/8) of the patients were confirmed p16+ by immunohistochemistry (IHC), while 25% (2/8) tested HPV+ by in situ hybridization (ISH). Diagnostic TORS was performed in 75% (6/8), while 25% (2/8) underwent direct laryngoscopy, with all primary tumors found in the oropharynx, 100% (8/8). Notably, 85.7% (6/7) of patients showed an unexpected elevation in total tumor mutational volume (TTMV) scores post-diagnostic procedure compared to baseline, with ctHPVDNA levels ranging from 30 to 2466, including one case where levels nearly quintupled. One patient had no post-diagnostic procedure TTMV score due to a negative baseline. However, in one other case, there was a negative post-procedure level. Among those with elevated post ctHPVDNA, 71.4% (5/7) underwent complete TORS excision, resulting in decreased postoperative ctHPVDNA levels in all patients, consistent with recent studies. Conclusion: This study provides insight that diagnostic procedures, such as TORS or direct laryngoscopy, in patients with p16+ HPV-mediated oropharyngeal cancer may lead to transient and unexpected elevations in ctHPVDNA levels, measured by TTMV scores. Although most patients showed a subsequent decrease in ctHPVDNA levels following a complete tumor resection, the observed post-diagnostic elevation emphasizes the importance of considering the timing of ctHPVDNA measurements. These findings suggest surgical manipulation may temporarily influence ctHPVDNA kinetics that could impact clinical decision-making and postoperative monitoring. Further research is needed to understand the implications of these transient elevations and optimizing the timing of ctHPVDNA assessments in clinical practice. Citation Format: Hlu Vang, Joanne Soo, Nikita Bedi, Andrea Garofalo, Michelle M Chen, Andrey Finegersh, Floyd Christopher Holsinger. Transient elevation of ctHPVDNA in human papilloma virus-mediated oropharynx squamous cell carcinoma patients following diagnostic surgical procedures [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A007.

As semiconductor manufacturing progresses to smaller process nodes, it is becoming increasingly difficult to climb the yield learning curve rapidly. The rate of yield learning dictates the growth and success of the semiconductor industry, and must be accelerated to fulfill competitive time-to-market, time-to-money and time-to-volume requirements. Software-based diagnosis plays a crucial role in yield learning. Diagnosis comprehends the test response of a failing circuit to determine the location, and sometimes, in addition, characterize the nature of a defect affecting the failing circuit. Besides identifying likely failure mechanisms and increasing the quality of chip testing, the feedback provided by diagnosis is used to select chips for physical failure analysis (PFA). PFA aims to visually examine a chip to characterize a defect, prevent similar defects in the future and, consequently, improve the design and manufacturing of a chip.However, PFA is often destructive, time- and cost-intensive, and not always successful. Diagnosis, on the other hand, is non-invasive and time- and cost-effective; moreover, it assists PFA and guides yield learning. The advantages of diagnosis, coupled with the diminishing performance of PFA with advancing technology, make it an encouraging facilitator for rapid yield learning.Therefore, the objective of diagnosis must be logic-level defect characterization to minimize (and ideally eliminate) the need for PFA, and accelerate yield learning. Logic characterization of a defect includes the derivation of its physical location and precise logic behavior. In this dissertation, a comprehensive diagnosis methodology is developed to actualize the aforementioned objective.The developed methodology comprises of three methods. LearnX/MD-LearnX is a physically-aware method that employs (a) the X-fault model to avert the elimination of a correct defect candidate and (b) machine learning to build a candidate-ranking model that learns the hidden correlations between the tester response and the defect candidates to pinpoint the correct candidate. PADLOC, which stands for Physically-Aware Defect LOcalization and Characterization, improves the physical location of a back-end defect (i.e., a defect that affects one or more interconnects and resides outside a standard cell) returned by LearnX/MD-LearnX by partitioning the defective net into physical subnets and identifying the subnets that influence defect excitation. In addition, PADLOC deduces the precise impact of a defect on the circuit functionality by examining its surrounding circuitry. NOIDA, which stands for NOise-resistant Intra-cell Diagnosis Approach, pinpoints the location of a defect within a failing standard cell implicated by LearnX/MD-LearnX. In contrast to prior work that typically constructs/employs a fault dictionary, NOIDA ascertains the location as well as the behavior of a front-end defect (i.e., a defect that resides inside a standard cell) by monitoring the logical activity of its intra-cell neighborhood. Additionally, NOIDA is resistant to circuit-level noise that may originate from potentially inaccurate transistor-level simulation. Results from numerous experiments reveal that our diagnosis methodology outperforms state-of-the-art commercial diagnosis. LearnX/MD-LearnX reports fewer defect candidates than commercial diagnosis for 69.4% silicon fail logs without losing accuracy. PADLOC implicates a smaller physical area for a defect for 47.2% silicon fail logs and attains at most 44X improvement. NOIDA reports an ideal diagnosis for 38.0% more front-end defects, when compared to leading-edge commercial diagnosis. In the presence of noise, NOIDA achieves an ideal diagnosis 7.6X more often.In summary, this dissertation endeavors to characterize a defect residing in a logic chip in terms of its precise physical location and logic behavior, which, consequently, most likely, enables rapid yield learning. The deployment of machine learning to pinpoint the correct candidate in LearnX/MD-LearnX, and the investigation of the neighborhood of a defect to determine its exact physical location and logic behavior in PADLOC and NOIDA are the novel components of this dissertation, and the reasons for its superiority over the state-of-the-art.

The present work reports data of the radiation exposure to the patient in various diagnostic and therapeutic interventional radiological (IR) procedures. The study includes 260 diagnostic and 195 therapeutic exposure data in 455 IR procedures. All the IR procedures were performed on a biplane angiographic machine in a tertiary care hospital. The radiation exposure was estimated from dose-area product (DAP), fluoroscopy time (FT), number of fluoroscopic runs, number of images and cumulative dose (CD) value recorded during the procedure. The data reported in the present study show significant variability in DAP values in diagnostic and therapeutic IR procedures. In diagnostic procedures, the minimum median DAP value is 8.93 Gy cm2 for upper limb angiography with mean FT of 2.7 min and maximum DAP value is 108.8 Gy cm2 for inferior vena cava angiography with mean FT of 12.55 min. For therapeutic procedures, the median value of DAP ranges from 2.43 Gy cm2 for sclerotherapy with mean FT 0.65 min to 267.23 Gy cm2 for coiling of cerebral aneurysm with mean FT of 60.52 min. The DAP value for each procedure was also correlated with FT, number of fluoroscopic runs, number of images and CD. The reported DAP values in this study are within the range of earlier published results which suggest that our finding provides at least approximate applicability to other hospitals. The third quartile DAP values of the procedures having significant number of patient data (n ≥ 10) serves as provisional reference values for the optimization of procedure protocols.

Objective:Cardiac catheterization remains a major source of radiation exposure for patients with congenital heart disease. This study reports the magnitude of radiation with a 3.75 frame per second (fps) pulse fluoroscopy rate and compares the reduction with the previous 15 fps protocol during cardiac catheterization for pediatric and adult congenital heart disease.Material and Methods:All diagnostic and interventional cardiac catheterization procedures from a single tertiary center were analyzed from January 1, 2014 to December 31, 2015, one year before and after implementing lower starting pulse fluoroscopy rates. The radiation dose was quantified as air kerma dose (mGy) and dose-area product (DAP; µGy/m2). Radiation exposure was analyzed for diagnostic and interventional procedures; the diagnostic group was subdivided into cyanotic and acyanotic patients, whereas the interventional group was subdivided according to the most common indications.Results:A total of 786 procedures were analyzed. The median fluoroscopy times and contrast amounts did not show a statistically significant difference between both periods (487 vs. 456 seconds and 42.5 vs. 45.3 cm3). The median air kerma for all procedures showed an 88% reduction after implementing lower pulse fluoroscopy rates (340-41 mGy). The doses were reduced significantly for diagnostic and interventional angiograms from 470 mGy and 162 mGy to 40 mGy and154 mGy. Among all patient groups, the most striking decrease was observed in the diagnostic procedures we use, of which fluoroscopy is more prominent than cine angiography.Conclusion:We claim that novel radiation dose reduction protocols could be easily applied without increasing fluoroscopy time or losing image quality.

Children with malignant lymphoma undergo many diagnostic procedures that involveexposure to ionising radiation. In addition, many, but by no means all, undergo furtherexposure to ionising radiation during radiotherapy. While therapeutic radiation exposuresare prescribed, the extent of radiation exposure arising from diagnostic procedures utilisedin such children is largely unknown. We completed an audit of the radiation doses arisingfrom diagnostic imaging procedures performed in a cohort of children with malignantlymphoma.The cumulative effective radiation dose associated with radiographic and radioisotopicprocedures was derived for 81 children and adolescents with malignant lymphoma duringtheir diagnosis, treatment and follow-up. Thirty-eight of the 42 patients (90%) withHodgkin lymphoma were alive at study termination, with follow-up periods ranging from1.9 to 11.7 years (median 5.3). Thirty-three of the 39 patients (85%) with non-Hodgkinlymphoma were alive at study termination with follow-up periods ranging from 2.4 to 12.3years (median 7.5). The median effective dose was 518 mSv for patients with Hodgkinlymphoma and 309 mSv for those with non-Hodgkin lymphoma. The maximumeffective dose was 1.7 Sv. The principal contributors to the effective dose werecomputed tomography (CT) and nuclear medicine imaging procedures using 67Ga. Protocols for the management of children and adolescents with malignant lymphomashould be reviewed in order to reduce the radiation detriment without loss of essentialdiagnostic information.

BackgroundSclerosing angiomatoid nodular transformation is a benign disorder of splenic tissue and is often mistaken as a potentially malignant entity in the diagnostic process. To the best of our knowledge, this is the first report of sclerosing angiomatoid nodular transformation mimicking metastasis of melanoma in the literature.Case presentationA 43-year-old white man presented with a newly found splenic mass 4 years ago to our Department of Gastroenterology. He was diagnosed as having a superficial spreading malignant melanoma localized at his left instep 7 years ago and was successfully treated with radical local resection. Several diagnostic procedures were conducted. Ultrasound showed a hypoechoic lesion in the inferior pole of his spleen with a diameter of 2 cm, blurred boundaries, and inhomogeneous interior pattern. Contrast-enhanced ultrasound was inconclusive and showed only discrete contrast enhancement of the lesion with accentuated nodule-like enrichment of the boundaries in the arterial phase. Computed tomography and magnetic resonance imaging scans showed two splenic lesions which were highly suspicious of metastasis. Magnetic resonance imaging of his head was inconspicuous. Bone scintigraphy showed no abnormal results. Fine-needle aspiration indicated metastasis of the above-mentioned malignant melanoma. We conducted a laparoscopic splenectomy. His intraoperative and postoperative course were uneventful. In contrast to the result of the fine-needle aspiration, the presence of metastasis of melanoma could not be confirmed. Histological analysis revealed nodule-like arrangement of fibroblasts with low cell density and a predominance of dilated capillaries, indicating sclerosing angiomatoid nodular transformation of the spleen.ConclusionsThere are no preoperative diagnostic imaging procedures which can definitely differentiate sclerosing angiomatoid nodular transformation from malignancies in cases of morphological and immunophenotypic variations of the specimen. Morphological and immunophenotypic variations of the specimen represent a diagnostic challenge and can mimic malignoma. As reported in our case, the specimen obtained by ultrasound-guided fine-needle aspiration led to the diagnosis of metastasis of melanoma. Splenectomy is often conducted due to a splenic mass suspicious of malignoma as described in our case or with unknown valency in different diagnostic imaging procedures.

It is generally accepted that septic conditions of the shoulder often lead to an earnest situation with joint damage. Because of the low incidence of shoulder infections there are only a few cases reported in the literature. Therefore, unlike joint infections of the knee no diagnostic and therapeutic standard procedure is documented for the shoulder. In a retrospective study the results of 15 patients with a surgical revision at the BG-Clinic-Bergmannsheil-Bochum between 1 January 1989 and 31 August 1999 after an infection of the shoulder joint were analyzed. We registered the following parameters: etiology, intervall until the first clinical symptoms, clinical signs, diagnostic procedure, intraoperative site (Gächter classification), and operative treatment. The diagnostic procedure followed an algorithm, including CRP-determination, ultrasound of the shoulder, ultrasound-guided aspiration and a Gram stain. If the result was positive, surgical joint revision followed. The infection stage was classified intraoperatively according to the criteria of the Gächter classification. Eight patients were reexamined after an average follow-up of 4.8 years. Fourteen infections followed injection. All patients demonstrated increasing CRP levels and a painful limited range of motion. In all Gram stains we detected bacterial organisms. The diagnosis of an acute infection according to the criteria of this diagnostic algorithm was verified intraoperatively in all 15 joints. Two patients with delayed admission died postoperatively due to septic multiorgan failure despite maximal treatment under intensive care conditions. If there are suspicious clinical symptoms after a typical anamnesis, we recommend an immediate diagnostic algorithm, including CRP determination, ultrasound of the shoulder, ultrasound-guided joint puncture and a Gram stain. If there is acute joint infection, time-consuming diagnostic procedures must be avoided because of the risk of secondary reduced joint mobility or life-threatening complications.

Antibiotic resistance is a key issue affecting public health, and diagnostic bacteriology laboratories are essential for prompt recognition of resistant isolates. Determination of susceptibility or resistance using phenotypic tests is a 'gold standard' against which newer technologies are compared in terms of performance, cost and ease of use. Molecular methods for detecting resistance are myriad, and are used widely in academia and in reference laboratories, but gaining a significant foothold in diagnostic laboratories is proving more difficult. However, if used widely in a diagnostic setting, these techniques would impact more directly on patient care and would be valuable infection control tools, e.g. by rapidly confirming patients colonized by resistant bacteria. The cost of molecular assays may be considered prohibitive, and this is compounded by the daunting variety of proprietary platforms available; most diagnostic laboratories would prefer to invest their capital and to train their staff in a single versatile technology. In a market that has no clear leader, many laboratories are understandably reluctant to gamble on making the correct choice. If molecular detection of resistance is to achieve wide acceptance, manufacturers must broaden the repertoires of their technologies, develop more off-the-shelf applications with in-built quality control, and make them suitable for laboratory personnel with no specialist expertise in molecular biology.

Background:Hypophosphatasia (HPP) is a rare genetic disorder (1-3/300,000 severe cases in Europe) caused by one or more mutations in the alkaline phosphatase (ALP) gene. Hypomineralization results in symptoms such as...

Objective To investigate the effect of impedance cardiography on rapid diagnosis of severe patients with dyspnea. Methods A blinded trial was conducted. All 80 cases of dyspnea in ICU were enrolled in the study from June 2014 to March 2016. Each patient will be routinely checked, such as routine blood test, liver and kidney function, electrolytes, electrocardiogram, chest X-ray, arterial blood gas analysis. According to the results of the examination, ICU physician diagnosed and treated the patients. All patients were treated with ICG hemodynamic monitoring, the person responsible for the ICG monitoring and recording the cardiac index (CI), stroke index (SI), systemic vascular resistance index (SVRI), systolic time ratio (STR), velocity index (VI) and thoracic fluid content (TFC), but ICU physicians blinded to the ICG data. After discharge from the hospital, the team of experts who did not participate in the treatment and did not know the results of the ICG integrated all the medical data, the final hospital diagnosis of each patient: cardiac or non cardiac dyspnea. To compare the time and results of ICG diagnosis and ICU physician diagnosis of dyspnea; According to the team′s final diagnosis, the sensitivity, specificity, positive predictive value and negative predictive value of ICG diagnosis and ICU physician diagnosis were calculated respectively, and the judgment ability of both cardiac and non cardiac dyspnea was analyzed. Results All 4 patients were excluded from the study because of unacquirable ICG data, and the final diagnosis of cardiac dyspnea was in 24 patients, and 52 were noncardiac dyspnea. The ICU physician diagnosed 20/24 patients correctly with final diagnosis of cardiac cause, and 40/52 with noncardiac cause. ICG correctly diagnosed 22/24 patients with cardiac cause, and 46/52 with noncardiac cause. Compared with the final diagnosis, the overall diagnostic accuracy by ICG was 89%(68/76) compared with 79% (60/76) for ICU physicians, with a statistically significant difference (P<0.05). ICG hemodynamic parameters showed low CI, SI and VI, high STR, SVRI and TFC in patients with cardiac dyspnea.There were significant differences in values of CI(2.00±0.95 vs. 3.00±0.72, P<0.001) STR(0.56±0.28 vs. 0.40±0.11, P<0.001), VI(31.8±14.7 vs. 42.2±15.8, P=0.008), TFC(40.6±14.4 vs. 32.4±14.0, P=0.021); SI(27.8±11.4 vs. 34.6±10.8, P=0.014), SVRI(2 952±1 191 vs. 2 124±801, P<0.001). between the cardiac and noncardiac groups, respectively. And there were significant differences in diagnosis time(0.47±0.34 vs. 1.57±1.14 h, P<0.00). ICG measurements demonstrated superior sensitivity (91.7% vs. 83.3%), specificity (88.5% vs. 76.9%), and positive and negative predictive values (78.6% vs. 62.5% and 95.8% vs. 90.9%, respectively) when compared with the ICU physician in the final diagnosis of cardiac vs. noncardiac cause of dyspnea. Conclusions ICG diagnosis of patients with severe dyspnea with superior sensitivity, specificity, positive predictive value and negative predictive value. ICU can help doctors quickly, effectively, accurately diagnose the cause of dyspnea as cardiac or noncardiac, to guide clinical treatment. Key words: Impedance cardiography; Severe patients; Dyspnea, cardiogenic; Noncardiac

Objective To evaluate the role of endoscopic ultrasound-guided fine needle aspiration （EUS-FNA） for diagnosing lesions of gastrointestinal tract and the nearby organs. Methods Clinical and pathological data of 161 EUS-FNA lesions in 133 consecutive patients were retrospectively analyzed. Resuits Of the 161 lesions, there were 142 solid lesions, 15 cystic lesions and 4 pancreatic solid-cystic lesions. EUS-FNA was performed at lesions of upper gastrointestinal tract, rectum and anal canal. 160 cytologic diagnoses （99. 4% ） were obtained in all 161 lesions. 143 histological diagnoses （97. 9% ） and 113 immunohistologieal diagnoses （77. 4% ） were obtained in 146 solid lesions （including 4 pancreatic solid-cystic ones）. Diagnosis rates of samples for immunohistology remained similar between 22-gauge and 19-gauge needles and also similar among different sites （ P 〉 0. 05 ）. But immunohistological diagnosis rate of smaller lesions （ 〈 1 cm） was lower than that of bigger ones （ 〉tl cm） （P 〈0.05）. The diagnosis rates of cytology,histology and pathology in solid lesions were 81.2% （ 120/146）, 82. 9% （121/146） and 89. 7% （ 131/ 146 ）, respectively. Size of needles and lesion location did not exert influence on diagnosis, but the diagnosis rate of smaller lesions （ 〈 1 cm） was lower than that of bigger ones （ 〉11 cm）. Cytological diagnosis was consistent with histological diagnosis （ x = 1. 0, P = 0. 00）, 11 cases that could not be diagnosed by cytology was confirmed by histology and 10 eases that could not diagnosed by histology was confirmed by cytology. There were no complications during the procedures. Conclusion EUS-FNA is a valuable diagnostic tool for lesions of gastrointestinal tract and nearby organs. The needle size and lesion site were not influential factors for diagnosis. Smaller lesions （ 〈 1 cm） yielded lower diagnosis rate than bigger ones （ 〉11 cm）. The cytologic diagnosis combined with histology can improve the diagnostic value of EUS-FNA. Key words: Endoscopic uhrasonography ; Neoplasma; Fine-needle aspiration

Diagnostic tests are of vital importance in a number of veterinary fields and are essential for decision-making by veterinary practioners, researchers and the veterinary authorities. The development and evaluation of laboratory diagnostic tests as well as the interpretation of test results engage a number of different veterinary disciplines including virologists, parasitologists, bacteriologists, laboratory experts, clinicians as well as epidemiologists and biostatisticians. This thesis was devised shortly after the section of epidemiology came into existence at the Vetsuisse Faculty end of 2009. The aim is to interrelate veterinary epidemiology - being closely linked to virology, parasitology, bacteriology and clinical medicine - with biostatistics. Thus allowing innovative concepts and recent software developments to provide solutions and answers in our veterinary field. After a brief introduction into diagnostic tests, the thesis is structured into three main parts. First, from a laboratory perspective, aspects of analytical sensitivity and specificity are illustrated by three peer-reviewed papers presenting practical applications of veterinary diagnostic tests for feline calicivirus and porcine parvovirus. Second, in the context of assessing agreement and method comparison studies, categorical test results are compared by Cohen’s k and continuous measurements by linear mixed effects models extending the classical use of Bland-Altman plots with limits of agreement. The former is illustrated in a publication on the diagnostic test Interferon-Gamma to classify bovines being infected with Mycobacterium bovis when analysing samples from the same animals in five different laboratories and from different anatomical locations. Two peer-reviewed papers aim to assess the agreement of serumspecific lipase, as a diagnostic test for feline pancreatitis with a commercial test kit and ultrasonographic findings. In the context of comparing continuous measurements, i.e. cardiac output and blood pressure measured directly and indirectly, two peer-reviewed paper illustrate the application of linear mixed effects models to simultaneously assess bias, precision and covariate information. Typical pitfalls arising in method comparison studies are summarised in a review paper. Building upon the previous parts, the third part adds to the existing knowledge by presenting novel and innovative approaches when assessing the performance of diagnostic tests in the absence of a perfect gold standard. So-called no gold standard models (NGS) are applied to assess the diagnostic test accuracies in the context of zoonotic diseases such as bovine tuberculosis, porcine toxoplasmosis as well as canine and vulpine echinococcosis. Additionally, these models are applied to assess diagnostic test accuracies to diagnose Brachyspira hyodysenteriae, an economically important disease in pigs. Furthermore, they are also utilised to assess diagnostic accuracies of diagnostic tools for subclinical mastitis in dairy cattle. In this part, Bayesian approaches are presented, together with technical aspects including conditional dependencies, Markov Chain Monte Carlo simulations and aspects of model selection. The innovative aspects and main novelty of the work presented in this thesis pertain to the incorporation of covariate information and random effects. Whereas covariate information in the form of risk factors has been included in statistical analyses since decades, considering random effects to account for clustering of animals at herd level just became possible with increased computational power. Nowadays dealing appropriately with the hierarchical structure of animal data is considered as good statistical practice and warranted in epidemiological studies to avoid biased results. However, diagnostic test studies including covariate information and random effects are scarce. The aim of this thesis is to fill this gap by showcasing a number of Bayesian latent class analyses for various infectious diseases in animals.

Hemophilia A is the most common hereditary hemorrhagic disease, which attracts great at-tention. Because we lack of effective curing methods for this disease, gene diagnosis and prenatal diagnosis ofhemophilia A become extremely important. The gene diagnosis includes direct gene diagnosis and indirect link-age analysis. The techniques of prenatal diagnosis for the disease have developed rapidly in resent years. Wereview the update on the gene diagnosis and prenatal diagnosis for Hemophilia A. Key words: Hemophilia A; Gene diagnosis; Prenatal diagnosis