IgM-Associated Cryoglobulinaemia

Cryoglobulinaemia is characterised by serum immunoglobulins that precipitate at temperatures below 37 ◦C and redissolve on warming. Monoclonal IgM immunoglobulin can be associated with type I and II cryoglobulinaemia with underlying Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance, or another non-Hodgkin lymphoma. In this research, we review the clinical characteristics of monoclonal IgM-associated cryoglobulinaemia and suggest a management approach for addressing them. Laboratory testing is critical as even a minimal amount of measurable cryoglobulin may result in symptoms. Accurate detection of cryoglobulins may be challenging, care must be taken with preanalytical variables, and repeated testing of monoclonal protein and cryoglobulins is indicated if clinical suspicion is high. Presentations range from asymptomatic to showing multisystem involvement, meaning that careful evaluation of the features and a thorough interrogation of organ systems and the underlying clone are critical. Immediate management is required for clinical red-flag features. Due to their rarity, data to inform treatment decisions are scant and collaborative research is imperative must be conducted to aid researchers in efforts to define optimal treatment strategies

Prevention and management of secondary central nervous system lymphoma

Secondary central nervous system (CNS) lymphoma (SCNSL) is defined by the involvement of the CNS, either at the time of initial diagnosis of systemic lymphoma or in the setting of relapse, and can be either isolated or with synchronous systemic disease. The risk of CNS involvement in patients with diffuse large B-cell lymphoma is approximately 5%; however, certain clinical and biological features have been associated with a risk of up to 15%. There has been growing interest in improving the definition of patients at increased risk of CNS relapse, as well as identifying effective prophylactic strategies to prevent it. SCNSL often occurs within months of the initial diagnosis of lymphoma, suggesting the presence of occult disease at diagnosis in many cases. The differing presentations of SCNSL create the therapeutic challenge of controlling both the systemic disease and the CNS disease, which uniquely requires agents that penetrate the blood-brain barrier. Outcomes are generally poor with a median overall survival of approximately 6 months in retrospective series, particularly in those patients presenting with SCNSL after prior therapy. Prospective studies of intensive chemotherapy regimens containing high-dose methotrexate, followed by hematopoietic stem cell transplantation have shown the most favorable outcomes, especially for patients receiving thiotepa-based conditioning regimens. However, a proportion of patients will not respond to induction therapies or will subsequently relapse, indicating the need for more effective treatment strategies. In this review we focus on the identification of high-risk patients, prophylactic strategies and recent treatment approaches for SCNSL. The incorporation of novel agents in immunochemotherapy deserves further study in prospective trials

Air quality in Mecca and surrounding holy places in Saudi Arabia during Hajj: initial survey.

The Arabian Peninsula experiences severe air pollution, the extent and sources of which are poorly documented. Each year in Saudi Arabia this situation is intensified during Hajj, the Holy Pilgrimage of Islam that draws millions of pilgrims to Mecca. An initial study of air quality in Mecca and surrounding holy sites during the 2012 Hajj (October 24-27) revealed strongly elevated levels of the combustion tracer carbon monoxide (CO, up to 57 ppmv) and volatile organic compounds (VOCs) along the pilgrimage route-especially in the tunnels of Mecca-that are a concern for human health. The most abundant VOC was the gasoline evaporation tracer i-pentane, which exceeded 1200 ppbv in the tunnels. Even though VOC concentrations were generally lower during a follow-up non-Hajj sampling period (April 2013), many were still comparable to other large cities suffering from poor air quality. Major VOC sources during the 2012 Hajj study included vehicular exhaust, gasoline evaporation, liquefied petroleum gas, and air conditioners. Of the measured compounds, reactive alkenes and CO showed the strongest potential to form ground-level ozone. Because the number of pilgrims is expected to increase in the future, we present emission reduction strategies to target both combustive and evaporative fossil fuel sources

Application of artificial neural networks for understanding and diagnosing the state of mastitis in dairy cattle

Bovine mastitis adversely affects the dairy industry around the world. This disease is caused by a diverse range of bacteria, broadly categorised as minor and major pathogens. In-line tools that help identify these bacterial groupings in the early stages of the disease are advantageous as timely decisions could be made before the cow develops any clinical symptoms. The first objective of this research was to identify the most informative milk parameters for the detection of minor and major bacterial pathogens. The second objective of this research was to evaluate the potential of supervised and unsupervised neural network learning paradigms for the detection of minor infected and major infected quarters in the early stages of the disease. The third objective was to evaluate the effects of different proportions of infected to non-infected cases in the training data set on the correct classification rate of the supervised neural network models as there are proportionately more non-infected cases in a herd than infected cases. A database developed at Lincoln University was used to achieve the research objectives. Starting at calving, quarter milk samples were collected weekly from 112 cows for a period of fourteen weeks, resulting in 4852 samples with complete records for somatic cell count (SCC), electrical resistance, protein percentage, fat percentage, and bacteriological status. To account for the effects of the stage of lactation on milk parameters with respect to days in milking, data was divided into three days in milk ranges. In addition, cow variation was accounted for by the sire family from which the cow originated and the lactation number of each cow. Data was pre-processed before the application of advanced analytical techniques. Somatic cell score (SCS) and electrical resistance index were derived from somatic cell count and electrical resistance, respectively. After pre-processing, the data was divided into training and validation sets for the unsupervised neural network modelling experiment and, for the supervised neural network modelling experiments, the data was divided into training, calibration and validation sets. Prior to any modelling experiments, the data was analysed using statistical and multivariate visualisation techniques. Correlations (p<0.05) were found between the infection status of a quarter and its somatic cell score (SCS, 0.86), electrical resistance index (ERI, -0.59) and protein percentage (PP, 0.33). The multivariate parallel visualisation analysis validated the correlation analysis. Due to significant multicolinearity [Correlations: SCS and ERI (-0.65: p<0.05); SCS and PP (0.32: p<0.05); ERI and PP (-0.35: p<0.05)], the original variables were decorrelated using principle component analysis. SCS and ERI were found to be the most informative variables for discriminating between non-infected, minor infected and major infected cases. Unsupervised neural network (USNN) model was trained using the training data set which was extracted from the database, containing approximately equal number of randomly selected records for each bacteriological status [not infected (NI), infected with a major pathogen (MJI) and infected with a minor pathogen (MNI)]. The USNN model was validated with the remaining data using the four principle components, days in milk (DIM), lactation number (LN), sire number, and bacteriological status (BS). The specificity of the USNN model in correctly identifying non infected cases was 97%. Sensitivities for correctly detecting minor and major infections were 89% and 80%, respectively. The supervised neural network (SNN) models were trained, calibrated and validated with several sets of training, calibration and validation data, which were randomly extracted from the database in such a way that each set has a different proportion of infected to non-infected cases ranging from 1:1 to 1:10. The overall accuracy of these models based on validation data sets gradually increased with increase in the number of non-infected cases in the data sets (80% for the 1:1, 84% for 1:2, 86% for 1:4 and 93% for 1:10). Specificities of the best models for correctly recognising non-infected cases for the four data sets were 82% for 1:1, 91% for 1:2, 94% for 1:4 and 98% for 1:10. Sensitivities for correctly recognising minor infected cases for the four data sets were 86% for 1:1, 76% for 1:2, 71% for 1:4 and 44% for 1:10. Sensitivities for correctly recognising major infected cases for the four data sets were 20% for 1:1, 20% for 1:2, 30% for 1:4 and 40% for 1:10. Overall, sensitivity for the minor infected cases decreased while that of major infected cases increased with increase in the number non-infected cases in the training data set. Due to the very low prevalence of MJI category in this particular herd, results for this category may be inconclusive. This research suggests that somatic cell score and electrical resistance index of milk were the most effective variables for detecting the infection status of a quarter followed by milk protein and fat percentage. The neural network models were able to differentiate milk containing minor and major bacterial pathogens based on milk parameters associated with mastitis. It is concluded that the neural network models can be developed and incorporated into milking machines to provide an efficient and effective method for the diagnosis of mastitis

Data on highway maintenance, rehabilitation, and mobility projects for integrated planning in Texas

State Highway Agencies (SHAs) have different functional groups that work towards improving the functional and physical performance of highway assets. These functional groups often propose multiple inter-related highway projects on the same network. However, the respective information systems of such functional groups lack interoperability capabilities between them. This data article is related to an earlier study by France-Mensah et al. (France-Mensah et al., 2017) that explored the integrated visualization of highway projects proposed by different functional groups working in the same highway agency. This dataset provides a spatially integrated set of maintenance and capital planning projects which is rarely available due to organizational silos which often exist in highway agencies. The data includes approximately 700 highway projects with over 16 attributes that includes spatial, temporal, cost, and description attributes. The highway projects are located in the Fort Worth District of the Texas Department of Transportation (TxDOT) which is responsible for a large network (approximately 9000 lane miles) of highway assets. The agency currently oversees around $4 billion in construction projects and spends around$120 million annually for asset preservation. An analysis of the fund allocations categorized by different project types for pavement and bridge assets is presented. The data presented can be used to compare competing approaches or policies for cross-asset allocation, spatial-temporal projects coordination, and safety planning in the infrastructure management domain.Civil, Architectural, and Environmental Engineerin

Prevention and management of secondary central nervous system lymphoma

Prevention; LymphomaPrevenció; LimfomaPrevención; LinfomaSecondary central nervous system (CNS) lymphoma (SCNSL) is defined by the involvement of the CNS, either at the time of initial diagnosis of systemic lymphoma or in the setting of relapse, and can be either isolated or with synchronous systemic disease. The risk of CNS involvement in patients with diffuse large B-cell lymphoma is approximately 5%; however, certain clinical and biological features have been associated with a risk of up to 15%. There has been growing interest in improving the definition of patients at increased risk of CNS relapse, as well as identifying effective prophylactic strategies to prevent it. SCNSL often occurs within months of the initial diagnosis of lymphoma, suggesting the presence of occult disease at diagnosis in many cases. The differing presentations of SCNSL create the therapeutic challenge of controlling both the systemic disease and the CNS disease, which uniquely requires agents that penetrate the blood-brain barrier. Outcomes are generally poor with a median overall survival of approximately 6 months in retrospective series, particularly in those patients presenting with SCNSL after prior therapy. Prospective studies of intensive chemotherapy regimens containing high-dose methotrexate, followed by hematopoietic stem cell transplantation have shown the most favorable outcomes, especially for patients receiving thiotepa-based conditioning regimens. However, a proportion of patients will not respond to induction therapies or will subsequently relapse, indicating the need for more effective treatment strategies. In this review we focus on the identification of high-risk patients, prophylactic strategies and recent treatment approaches for SCNSL. The incorporation of novel agents in immunochemotherapy deserves further study in prospective trials

Characterization of carbon monoxide, methane and nonmethane hydrocarbons in emerging cities of Saudi Arabia and Pakistan and in Singapore

We investigate the composition of 63 C2-C10 nonmethane hydrocarbons (NMHCs), methane (CH4) and carbon monoxide (CO), in Jeddah, Mecca, and Madina (Saudi Arabia), in Lahore, (Pakistan), and in Singapore. We established a database with which to compare and contrast NMHCs in regions where ambient levels and emissions are poorly characterized, but where conditions are favorable to the formation of tropospheric ozone, and where measurements are essential for improving emission inventories and modeling. This dataset will also serve as a base for further analysis of air pollution in Western Saudi Arabia including, but not limited to, the estimation of urban emissions and long range pollution transport from these regions. The measured species showed enhanced levels in all Saudi Arabian cities compared to the local background but were generally much lower than in Lahore. In Madina, vehicle exhaust was the dominant NMHC source, as indicated by enhanced levels of combustion products and by the good correlation between NMHCs and CO, while in Jeddah and Mecca a combination of sources needs to be considered. Very high NMHC levels were measured in Lahore, and elevated levels of CH4 in Lahore were attributed to natural gas. When we compared our results with 2010 emissions from the MACCity global inventory, we found discrepancies in the relative contribution of NMHCs between the measurements and the inventory. In all cities, alkenes (especially ethene and propene) dominated the hydroxyl radical (OH) reactivity (kOH) because of their great abundance and their relatively fast reaction rates with OH

Gilteritinib monotherapy as a transplant bridging option for high risk FLT3-mutated AML with t(6;9)(p23;q34.1);DEK-NUP214 in morphological but not cytogenetic or molecular remission following standard induction chemotherapy

We report a case of FLT3-mutated AML with t(6;9) in which induction chemotherapy with DA and midostaurin failed to achieve complete cytogenetic or molecular remission. Due to the COVID-19 pandemic and co-existing cellulitis, monotherapy with the selective FLT3-inhibitor gilteritinib was used as an alternative consolidation treatment option rather than further intensive chemotherapy. Gilteritinib was able to achieve complete molecular and cytogenetic remission despite the additional cytogenetic abnormality. This case provides supporting evidence for the use of single agent gilteritinib in high-risk primary refractory FLT3-mutated AML with t(6;9) prior to transplantation

Expression of Growth Factors and Growth Factor Receptor in Non-healing and Healing Ischaemic Ulceration

AbstractObjectivesTo characterise the histological and cytokinetic characteristics of purely ischaemic ulcers and the processes that underpin healing following successful revascularisation.DesignProspective observational study.Materials and methodsBiopsies were taken immediately pre- and 6 weeks following successful revascularisation of solely ischaemic ulceration. They were evaluated for morphological differences using H&E staining for the platelet derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), TGFβreceptorIII (TGFβRIII), transforming growth factor beta 1 and 3 (TGFβ1 and TGFβ3) and von Willebrand factor (vWF) expression using immunohistochemistry. Localisation and quantification of these growth factors and receptors was assessed systematically by three independent investigators who were blinded to the timing of biopsy.ResultsPre-operatively, small vessel vasculitis, necrosis and infection with a profuse neutrophil and macrophage infiltrate was observed in all samples. Post-operative biopsies revealed a proliferation of new capillaries in and around the ulcer edge and base. vWF staining confirmed an endothelial layer within these new vessels. Following successful revascularisation there was less infection and inflammation with minimal vasculitis. These newly formed capillaries had increased staining for TGFβ3, PDGFR and TGFβRIII with staining for PDGFR also localised to dermal fibroblasts which were larger and more numerous. Accelerated epithelial cell proliferation was observed with detachment from the underlying dermis.ConclusionsHealing of purely ischaemic ulcers is characterised by vasculogenesis associated with increased presence of the proangiogenic cytokines PDGF and TGFβ3. These findings show promise for the use of growth factor manipulation to aid healing in ischaemic ulcers