Cascade impactors are essential for measuring the aerodynamic particle size distribution delivered by metered dose, dry powder, and similar inhalable drug products. For quality control of used ...impactors, periodic optical inspection of the nozzles of each impactor stage (stage mensuration) is currently the only method sufficiently precise to test whether used impactors are suitable for continued use, in accord with pharmacopeial standards. Here, we demonstrate a new method for quality control of used impactors. The method combines stage-wise pressure-drop measurement with a critical flow venturi (CFV) for air flow management. This technique avoids the unacceptably large uncertainty in conventional air flow rate measurements and instead relies on pressure and temperature measurement upstream of the CFV. These measurements can be made precisely with affordable equipment.
We placed a toroidally shaped CFV downstream of a Next Generation Impactor™** (NGI) and precisely measured the stagnation pressure (±0.02%) and temperature (±0.03%) upstream of this CFV at impactor inlet flow rates close to 60 L/min. Pressure-drop measurements (±0.25%) at stages 3-7 and the micro-orifice collector were made with capacitive diaphragm transducers and with a special lid to the NGI that allowed pneumatic connection to the interstage passageways before and after each impactor stage.
The measured pressure drop values matched, to fractional percentage precision, those predicted by the incompressible flow theory through the nozzles and the compressible flow theory through the CFV.
Practical equipment has been assembled that measures, to fractional percentage precision, the pressure drop through impactor nozzles at precisely managed flow conditions. The experimental results support the relevant flow principles. The results, thereby, support the use of this method for quantifying whether used impactor stages are suitable for continued use in the testing of registered inhalable drug products, in accord with pharmacopeial standards.
Lean Six Sigma is a powerful methodology that reduces waste and variation in an organization and ultimately minimizes operating costs, optimizes productivity, and maximizes customer satisfaction. The ...success stories speak for themselves, but not all LSS stories have a happy ending, and a large body of scholarly research shows why. What is needed now is a set of accessible general guidelines for organizations seeking to implement and sustain such a powerful, but at times perilous, continuous improvement strategy. The Ten Commandments of Lean Six Sigma provides just that, offering guidance from the perspective of practitioners, researchers and academics who have been involved in training, teaching, researching and consulting on various topics of quality and continuous improvement such as Lean, Six Sigma and LSS. Delving into the cutting edge of business process enhancement, this book is an essential and practical guide for senior managers and executives who want to achieve operational and service excellence in manufacturing, service and public sector organizations of any size.
Semen analysis is characterized by high levels of intra- and inter-laboratory variability, due to a low level of standardization, high subjectivity of the assessments, and problems with automated ...procedures. To improve consistency of laboratory results, quality control and training of technicians are important requisites. The goals of this study are to evaluate the results of an external quality control (EQC) program and standardized training by ESHRE Basic Semen Analysis Courses (BSAC) on the variability in manual assessments of semen parameters. We performed retrospective analyses of (1) the interlaboratory variability in the Dutch EQC program and (2) the interobserver variability in BSACs for concentration, motility, and morphology assessments. EQC data showed that the interlaboratory coefficient of variation (CV) for concentration assessment decreased (range from 24.0%-97.5% to 12.7%-20.9%) but not for morphology and motility assessments. Concentration variability was lower if improved Neubauer hemocytometers were used. Morphology assessment showed highest CVs (up to 375.0%), with many outliers in the period of 2007-2014. During BSAC, a significant reduction of interobserver variability could be established for all parameters (P < 0.05). The absence of an effect in the EQC program for motility and morphology might be explained by respectively the facts that motility assessment was introduced relatively late in the EQC program (since 2013) and that criteria for morphology assessment changed in time. BSAC results might have been influenced by the pretraining level of participants and the influence of external factors. Both EQC and training show positive effects on reducing variability. Increased willingness by laboratories to change their methods toward standards may lead to further improvements.
Water quality surveillance systems are hardly applied in rural contexts. To provide a comprehensive analysis of drinking-water quality in two rural settlements in the Colombian Caribbean ...drinking-water samples were collected and analyzed from storage containers in 42 homes. The results of physical, chemical, and microbiological analyses of the water samples were compared with values established by the World Health Organization (WHO) Guidelines for Drinking-water Quality, and Colombian regulations. The Kruskal–Wallis test was applied to compare each parameter for supply source, season (rainy or dry), settlement, and types of storage. Drinking-water Quality Risk Index (IRCA) was calculated for each of the samples. The water supply sources were varied: well (33.3%), rainwater (23.8%), artificial pond (23.8%), and river (19.0%). One-hundred percent of the samples contained
Escherichia coli
and
total coliforms
. The IRCA varied between 57.3 and 83.9, with a median of 72.9. Eighty-eight percent of the samples exhibited high risk levels (35.1 < IRCA < 80.0) and 12% were unsanitary (80.1 < IRCA < 100.0). Artificial pond water was the source of supply with the worst IRCA (83.79). Drinking water in the El Cascajo and La Delfina settlements does not meet international and national drinking-water standards. A change is required whereby monitoring and quality control policies take into account the reality of rural settings.
Moving Average Algorithms (MAA) have been widely recommended for use in Patient Based Real Time Quality Control applications (PBRTQC) to supplement or replace traditional Internal Quality Control ...(IQC) techniques. A recent “proof of concept” study recommends applying MAAs to IQC data to replace traditional IQC procedures because they “outperform Westgard Rules,” which is a current standard of practice for IQC.
We generated power curves for multi-rule procedures with 2 and 4 control measurements per QC event, as well as a Simple Moving Average having block sizes of 5, 10, and 20 control measurements. We also assessed time to detection in terms of the Average Number of QC Events required to detect different sizes of systematic errors.
As expected, the more control measurements included in the control technique, the better the error detection. However, when QC performance is considered on the Sigma Scale, high Sigma methods require only 1 or 2 control measurements to detect medically important systematic errors. MAAs have very low ability to detect error at the first few QC events following shift, so they suffer a lag phase in detecting medically important errors. MAAs are most useful for methods having 4.0 Sigma performance or less. Even then, large systematic shifts are more quickly detected by simple single and multirule procedures.
Choice of control techniques (rules, means, ranges, etc.) should consider the Sigma-metric of the method. For methods having Sigmas of 4 or greater, traditional single rule and multirule procedures with Ns up to 4 are most effective; below 4 Sigma, a multirule coupled with a Simple Moving Average (SMA) rule with Ns of 4 to 8 can improve error detection.
S-nitrosylation, a prototypic redox-based posttranslational modification, is frequently dysregulated in disease. S-nitrosoglutathione reductase (GSNOR) regulates protein S-nitrosylation by ...functioning as a protein denitrosylase. Deficiency of GSNOR results in tumorigenesis and disrupts cellular homeostasis broadly, including metabolic, cardiovascular, and immune function. Here, we demonstrate that GSNOR expression decreases in primary cells undergoing senescence, as well as in mice and humans during their life span. In stark contrast, exceptionally long-lived individuals maintain GSNOR levels. We also show that GSNOR deficiency promotes mitochondrial nitrosative stress, including excessive S-nitrosylation of Drp1 and Parkin, thereby impairing mitochondrial dynamics and mitophagy. Our findings implicate GSNOR in mammalian longevity, suggest a molecular link between protein S-nitrosylation and mitochondria quality control in aging, and provide a redox-based perspective on aging with direct therapeutic implications.
Effective water quality prediction techniques are essential for the sustainable development of water resources and implementation of emergency response mechanisms. However, the water environment ...conditions are complex, and the presence of a large amount of noise in the water quality data makes it difficult to reveal the long-term trends or cycles of the data, affecting the acquisition of serial correlation in the data. In addition, the loss function based on the vertical Euclidean distance will produce a prediction lag problem, and it is difficult to make an accurate multi-step prediction of water quality series. This paper presents a multi-step water quality prediction model for watersheds that combines Savitzky-Golay (SG) filter with Transformer optimized networks. Among them, the SG filter highlights data trend change and improves sequence correlation by smoothing the potential noise of original data. The transformer network adopts a sequence-to-sequence framework, which contains a position encoding module and a self-attentive mechanism to perform multi-step prediction while effectively obtaining the sequence correlation. Moreover, the DIstortion Loss including shApe and TimE (DILATE) loss function is introduced into the model to solve the problem of prediction lag from two aspects of shape error and time error to improve the model’s generalization ability. An example validates the model with the benchmark model at four monitoring stations in the Lanzhou section of the Yellow River basin in China. The results show that the predictions of the proposed model have the correct shape, temporal positioning, and the best accuracy in a multi-step prediction task for four sites. It can provide a decision-making basis for comprehensive water quality control and pollutant control in the basin.
Graphical abstract
IntroductionAtraumatic needles are associated with a decreased incidence of postdural-puncture headache. They also reduce the need for additional treatment and have similar efficacy to conventional ...needles. The aim of this Quality Improvement Project (QIP) was to encourage the use of atraumatic needles in Neurology ambulatory care by developing a sustainable Lumbar Puncture (LP) training method.MethodsA specialised atraumatic needle training video was guru.kumar@nhs.net created for junior doctors starting in Neurology. This accompanied further teaching and opportunities to practice LPs on a simulation mannequin under supervision. Atraumatic needles were added to standard stock and supply was ensured.Two audit cycles recorded the number of LPs performed using an atraumatic needle. Patient age, body mass index, length of stay, pain experienced and any need for image guidance were also recoded. Junior doctor confidence was measured before and after training.Results81 LPs were performed in the first cycle, 83 in the second. Atraumatic needle use increased from 26% to 50% between cycles. Junior doctor confidence increased with training from 2/10 to 8/10 (p=0.02).ConclusionsDedicated induction teaching and observed simulation practice increased junior doctors’ confidence in, and frequency of, the use of atraumatic needles.
Introduction
The metabolomics quality assurance and quality control consortium (mQACC) evolved from the recognized need for a community-wide consensus on improving and systematizing quality assurance ...(QA) and quality control (QC) practices for untargeted metabolomics.
Objectives
In this work, we sought to identify and share the common and divergent QA and QC practices amongst mQACC members and collaborators who use liquid chromatography-mass spectrometry (LC–MS) in untargeted metabolomics.
Methods
All authors voluntarily participated in this collaborative research project by providing the details of and insights into the QA and QC practices used in their laboratories. This sharing was enabled via a six-page questionnaire composed of over 120 questions and comment fields which was developed as part of this work and has proved the basis for ongoing mQACC outreach.
Results
For QA, many laboratories reported documenting maintenance, calibration and tuning (82%); having established data storage and archival processes (71%); depositing data in public repositories (55%); having standard operating procedures (SOPs) in place for all laboratory processes (68%) and training staff on laboratory processes (55%). For QC, universal practices included using system suitability procedures (100%) and using a robust system of identification (Metabolomics Standards Initiative level 1 identification standards) for at least some of the detected compounds. Most laboratories used QC samples (>86%); used internal standards (91%); used a designated analytical acquisition template with randomized experimental samples (91%); and manually reviewed peak integration following data acquisition (86%). A minority of laboratories included technical replicates of experimental samples in their workflows (36%).
Conclusions
Although the 23 contributors were researchers with diverse and international backgrounds from academia, industry and government, they are not necessarily representative of the worldwide pool of practitioners due to the recruitment method for participants and its voluntary nature. However, both questionnaire and the findings presented here have already informed and led other data gathering efforts by mQACC at conferences and other outreach activities and will continue to evolve in order to guide discussions for recommendations of best practices within the community and to establish internationally agreed upon reporting standards. We very much welcome further feedback from readers of this article.
Chinese medicine (CM) is usually prescribed as CM formula to treat disease. The lack of effective research approach makes it difficult to elucidate the molecular mechanisms of CM formula owing to its ...complicated chemical compounds. Network pharmacology is increasingly applied in CM formula research in recent years, which is identified suitable for the study of CM formula. In this review, we summarized the methodology of network pharmacology, including network construction, network analysis and network verification. The aim of constructing a network is to achieve the interaction between the bioactive compounds and targets and the interaction between various targets, and then find out and validate the key nodes via network analysis and network verification. Besides, we reviewed the application in CM formula research, mainly including targets discovery, bioactive compounds screening, toxicity evaluation, mechanism research and quality control research. Finally, we proposed prospective in the future and limitations of network pharmacology, expecting to provide new strategy and thinking on study for CM formula.
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