Generic Programming with Multiple Parameters

Background: Distinguishing active Clostridioides difficile infection (CDI) from asymptomatic colonization remains a challenging task in the era of PCR testing. Inappropriate testing leads to overtesting and overdiagnosis, inadvertent treatment, and isolation in addition to laboratory identified (LabID) events, leading to increased incidence to hospital-onset CDI (HO-CDI). The institution has a nurse-driven C. difficile test ordering protocol, and we noted a significant increase in the HO-CDI incidence in 2017 due to inappropriate testing, with rates as high as 0.94 per 1,000 patient days. Methods: In September 2017, a multidisciplinary team reviewed and initiated algorithm-based testing with mandatory audit and review by infection preventionists (IPs) under the guidance of an ID physician of all ordered tests. They reviewed the adequacy and legitimacy of order for multiple parameters, including minimum 3 loose stools in 24 hours, use of laxatives in last 24 hours, consistency of the sample, presence of at least 1 clinical parameters (ie, fever, abdominal pain, leukocytosis, sepsis, or septic shock), recent or concomitant antibiotic use, recent PCR testing in the last 14 days, and chart review for medical and/or surgical history. The IPs served as the gatekeepers to testing and rejected the samples that were deemed inappropriate. Ambiguous cases were discussed with the ID specialist. On the microscope lab side, all specimens sent were batched to be run twice a day at 8:30 a.m. and 2:30 p.m., and testing was performed only on the samples cleared by infection preventionists. Results: The number of PCR tests completed in the comparison quarter of 2016 was 220, which decreased to 157 tests in 2017 with a reduction of 28%. After a full year of implementation of the diagnostic stewardship protocol, the number of completed PCR tests decreased to 626 from 940 PCR tests in 2016, with an overall 34% decrease in testing. In the year following the implementation of diagnostic stewardship, HO-CDI decreased from 60 events in 2017 to 43 events in 2018, with a reduction of 28%. Subsequently, HO-CDI further decreased in 2019 from 43 to 28, with a reduction of 35%. Since the implementation of the project in 2017, HO-CDIs have decreased by 54% overall. The reduction in 314 C. difficile PCR tests in the first year led to a savings of $8,300 in laboratory testing supplies. The reduction of HO CDI by 17 led to cost avoidance of $293,420. Conclusions: Our experience shows that the IP-run diagnostic stewardship program was highly successful in streamlining testing, with cost savings on several fronts.Funding: NoneDisclosures: NoneDisclosures:Commercial Company : If I am presenting research funded by a commercial company, the information presented will be based on generally accepted scientific principals and methods, and will not promote the commercial interest of the funding company.DisagreeRaghavendra Tirupathi

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Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)54192-2 ◽

1993 ◽

Vol 268 (1) ◽

pp. 591-600

Author(s):

S. Mader ◽

P. Leroy ◽

J.Y. Chen ◽

P. Chambon

Keyword(s):

Retinoic Acid ◽

Nuclear Receptors ◽

Retinoic Acid Receptors ◽

Response Element ◽

Retinoid X Receptors ◽

Response Elements ◽

Multiple Parameters ◽

X Receptors

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SOFA Score, Hemodynamics and Body Temperature Allow Early Discrimination between Porcine Peritonitis-Induced Sepsis and Peritonitis-Induced Septic Shock

Journal of Personalized Medicine ◽

10.3390/jpm11030164 ◽

2021 ◽

Vol 11 (3) ◽

pp. 164

Author(s):

Mahmoud Al-Obeidallah ◽

Dagmar Jarkovská ◽

Lenka Valešová ◽

Jan Horák ◽

Jan Jedlička ◽

...

Keyword(s):

Septic Shock ◽

Body Temperature ◽

Sofa Score ◽

Porcine Model ◽

Venous Blood ◽

Mixed Venous Blood ◽

Mechanically Ventilated ◽

Multiple Parameters ◽

Failure Assessment ◽

Sepsis And Septic Shock

Porcine model of peritonitis-induced sepsis is a well-established clinically relevant model of human disease. Interindividual variability of the response often complicates the interpretation of findings. To better understand the biological basis of the disease variability, the progression of the disease was compared between animals with sepsis and septic shock. Peritonitis was induced by inoculation of autologous feces in fifteen anesthetized, mechanically ventilated and surgically instrumented pigs and continued for 24 h. Cardiovascular and biochemical parameters were collected at baseline (just before peritonitis induction), 12 h, 18 h and 24 h (end of the experiment) after induction of peritonitis. Analysis of multiple parameters revealed the earliest significant differences between sepsis and septic shock groups in the sequential organ failure assessment (SOFA) score, systemic vascular resistance, partial pressure of oxygen in mixed venous blood and body temperature. Other significant functional differences developed later in the course of the disease. The data indicate that SOFA score, hemodynamical parameters and body temperature discriminate early between sepsis and septic shock in a clinically relevant porcine model. Early pronounced alterations of these parameters may herald a progression of the disease toward irreversible septic shock.

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Staging for generic programming in space and time

ACM SIGPLAN Notices ◽

10.1145/3170492.3136060 ◽

2017 ◽

Vol 52 (12) ◽

pp. 15-28

Author(s):

Georg Ofenbeck ◽

Tiark Rompf ◽

Markus Püschel

Keyword(s):

Generic Programming ◽

Space And Time

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Conventional, High-Resolution and Imaging Flow Cytometry: Benchmarking Performance in Characterisation of Extracellular Vesicles

Biomedicines ◽

10.3390/biomedicines9020124 ◽

2021 ◽

Vol 9 (2) ◽

pp. 124

Author(s):

Jaco Botha ◽

Haley R. Pugsley ◽

Aase Handberg

Keyword(s):

Flow Cytometry ◽

High Resolution ◽

Extracellular Vesicles ◽

Single Particles ◽

Multiple Parameters ◽

Imaging Flow Cytometry ◽

Highly Sensitive ◽

Individual Project ◽

Benchmarking Performance ◽

High Throughput Manner

Flow cytometry remains a commonly used methodology due to its ability to characterise multiple parameters on single particles in a high-throughput manner. In order to address limitations with lacking sensitivity of conventional flow cytometry to characterise extracellular vesicles (EVs), novel, highly sensitive platforms, such as high-resolution and imaging flow cytometers, have been developed. We provided comparative benchmarks of a conventional FACS Aria III, a high-resolution Apogee A60 Micro-PLUS and the ImageStream X Mk II imaging flow cytometry platform. Nanospheres were used to systematically characterise the abilities of each platform to detect and quantify populations with different sizes, refractive indices and fluorescence properties, and the repeatability in concentration determinations was reported for each population. We evaluated the ability of the three platforms to detect different EV phenotypes in blood plasma and the intra-day, inter-day and global variabilities in determining EV concentrations. By applying this or similar methodology to characterise methods, researchers would be able to make informed decisions on choice of platforms and thereby be able to match suitable flow cytometry platforms with projects based on the needs of each individual project. This would greatly contribute to improving the robustness and reproducibility of EV studies.

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Critical Aspects Concerning the Development of a Pooling Approach for SARS-CoV-2 Diagnosis Using Large-Scale PCR Testing

Viruses ◽

10.3390/v13050902 ◽

2021 ◽

Vol 13 (5) ◽

pp. 902

Author(s):

Daniel Cruceriu ◽

Oana Baldasici ◽

Loredana Balacescu ◽

Stefana Gligor-Popa ◽

Mirela Flonta ◽

...

Keyword(s):

Large Scale ◽

Rna Extraction ◽

Diagnostic Assay ◽

Assay Sensitivity ◽

Infected People ◽

Multiple Parameters ◽

Accurate Procedure ◽

Manual Methods ◽

Pooling Strategy ◽

Critical Aspects

The primary approach to controlling the spread of the pandemic SARS-CoV-2 is to diagnose and isolate the infected people quickly. Our paper aimed to investigate the efficiency and the reliability of a hierarchical pooling approach for large-scale PCR testing for SARS-CoV-2 diagnosis. To identify the best conditions for the pooling approach for SARS-CoV-2 diagnosis by RT-qPCR, we investigated four manual methods for both RNA extraction and PCR assessment targeting one or more of the RdRp, N, S, and ORF1a genes, by using two PCR devices and an automated flux for SARS-CoV-2 detection. We determined the most efficient and accurate diagnostic assay, taking into account multiple parameters. The optimal pool size calculation included the prevalence of SARS-CoV-2, the assay sensitivity of 95%, an assay specificity of 100%, and a range of pool sizes of 5 to 15 samples. Our investigation revealed that the most efficient and accurate procedure for detecting the SARS-CoV-2 has a detection limit of 2.5 copies/PCR reaction. This pooling approach proved to be efficient and accurate in detecting SARS-CoV-2 for all samples with individual quantification cycle (Cq) values lower than 35, accounting for more than 94% of all positive specimens. Our data could serve as a comprehensive practical guide for SARS-CoV-2 diagnostic centers planning to address such a pooling strategy.

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Airway Abnormalities in Adult Mucopolysaccharidosis and Development of Salford Mucopolysaccharidosis Airway Score

Journal of Clinical Medicine ◽

10.3390/jcm10153275 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3275

Author(s):

Chaitanya Gadepalli ◽

Karolina M. Stepien ◽

Reena Sharma ◽

Ana Jovanovic ◽

Govind Tol ◽

...

Keyword(s):

Airway Disease ◽

Lysosomal Storage ◽

Cross Sectional ◽

Airway Narrowing ◽

3 Dimensional ◽

Multiple Parameters ◽

Validated Questionnaire ◽

Dimensional Reconstruction ◽

Cross Sectional Imaging ◽

Airway Abnormalities

(1) Background: Mucopolysaccharidoses (MPS) are a heterogeneous group of lysosomal storage disorders caused by the absence of enzymes required for degradation of glycosaminoglycans (GAGs). GAGs deposition in tissues leads to progressive airway narrowing and/or tortuosity. Increased longevity of patients has posed newer problems, especially the airway. This study aims to characterise various airway abnormalities in adult MPS from a regional centre and proposes a method to quantify the severity of the airway disease. (2) Methods: Retrospective analysis by case notes review, clinical examination, endoscopy, cross-sectional imaging, 3-dimensional reconstruction, and physiological investigations were used to assess the airway abnormalities. Quantitative assessment of the airway severity was performed a validated questionnaire of 15 parameters to derive Salford Mucopolysaccharidosis Airway Score (SMAS). (3) Results: Thirty-one adult MPS patients (21M/ 9F; median 26.7 years; range 19–42 years) were reviewed. There were 9 MPS I, 12 MPS II, 2 MPS III, 5 MPS IV, 2 MPS VI, and 1 MPS VII. Airway abnormalities in each MPS type are described. Patients scoring more than 35 on SMAS had some form of airway intervention. The area under curve of 0.9 was noted at a score of 25, so SMAS more than 25 may predict a difficult airway and potential to have complications. Pearson’s correlation between SMAS and height, weight, BMI were poor (p < 0.05). (4) Conclusions: Airway abnormalities in adult MPS are varied and complex. Assessment of the airway should be holistic and include multiple parameters. An objective multidimensional score such as SMAS may help to predict and manage difficult airways warranting further investigation and validation.

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Cellulose Derived Graphene/Polyaniline Nanocomposite Anode for Energy Generation and Bioremediation of Toxic Metals via Benthic Microbial Fuel Cells

Polymers ◽

10.3390/polym13010135 ◽

2020 ◽

Vol 13 (1) ◽

pp. 135

Author(s):

Asim Ali Yaqoob ◽

Mohamad Nasir Mohamad Ibrahim ◽

Khalid Umar ◽

Showkat Ahmad Bhawani ◽

Anish Khan ◽

...

Keyword(s):

Fuel Cells ◽

Current Density ◽

Toxic Metals ◽

Microbial Fuel Cells ◽

Organic Substrate ◽

Synthetic Wastewater ◽

Multiple Parameters ◽

Pani Composite ◽

Industrial Level ◽

Modified Graphene

Benthic microbial fuel cells (BMFCs) are considered to be one of the eco-friendly bioelectrochemical cell approaches nowadays. The utilization of waste materials in BMFCs is to generate energy and concurrently bioremediate the toxic metals from synthetic wastewater, which is an ideal approach. The use of novel electrode material and natural organic waste material as substrates can minimize the present challenges of the BMFCs. The present study is focused on cellulosic derived graphene-polyaniline (GO-PANI) composite anode fabrication in order to improve the electron transfer rate. Several electrochemical and physicochemical techniques are used to characterize the performance of anodes in BMFCs. The maximum current density during polarization behavior was found to be 87.71 mA/m2 in the presence of the GO-PANI anode with sweet potato as an organic substrate in BMFCs, while the GO-PANI offered 15.13 mA/m2 current density under the close circuit conditions in the presence of 1000 Ω external resistance. The modified graphene anode showed four times higher performance than the unmodified anode. Similarly, the remediation efficiency of GO-PANI was 65.51% for Cd (II) and 60.33% for Pb (II), which is also higher than the unmodified graphene anode. Furthermore, multiple parameters (pH, temperature, organic substrate) were optimized to validate the efficiency of the fabricated anode in different environmental atmospheres via BMFCs. In order to ensure the practice of BMFCs at industrial level, some present challenges and future perspectives are also considered briefly.

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Sepsis Diagnostics: Intensive Care Scoring Systems Superior to MicroRNA Biomarker Testing

Diagnostics ◽

10.3390/diagnostics10090701 ◽

2020 ◽

Vol 10 (9) ◽

pp. 701

Author(s):

Fabian Link ◽

Knut Krohn ◽

Anna-Maria Burgdorff ◽

Annett Christel ◽

Julia Schumann

Keyword(s):

Intensive Care ◽

Scoring Systems ◽

Digital Pcr ◽

Absolute Quantification ◽

Medical Problem ◽

Control Group ◽

Multiple Parameters ◽

Sepsis Diagnosis ◽

Intensive Care Patients ◽

Healthy Control

Sepsis represents a serious medical problem accounting for numerous deaths of critically ill patients in intensive care units (ICUs). An early, sensitive, and specific diagnosis is considered a key element for improving the outcome of sepsis patients. In addition to classical laboratory markers, ICU scoring systems and serum miRNAs are discussed as potential sepsis biomarkers. In the present prospective observational study, the suitability of miRNAs in sepsis diagnosis was tested based on proper validated and normalized data (i.e., absolute quantification by means of Droplet Digital PCR (ddPCR)) in direct comparison to classical sepsis markers and ICU scores within the same patient cohort. Therefore, blood samples of septic intensive care patients (n = 12) taken at day of admission at ICU were compared to non-septic intensive care patients (n = 12) and a healthy control group (n = 12). Our analysis indicates that all tested biomarkers have only a moderate informative power and do not allow an unequivocal differentiation between septic and non-septic ICU patients. In conclusion, there is no standalone laboratory parameter that enables a reliable diagnosis of sepsis. miRNAs are not superior to classical parameters in this respect. It seems recommendable to measure multiple parameters and scores and to interpret them with regard to the clinical presentation.

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