Near-source error sensor strategies for active vibration isolation of machines

Due to lightweight construction of vehicles and ships, the reduction of structure borne interior noise problems with passive isolation of engine vibrations might be not sufficient. To improve the isolation, a combination of passive and active isolation techniques can be used (so-called hybrid isolation). This paper focusses on the influence of the sensor positions on the performance of the active isolation. In general two strategies can be distinguished: sensors located in the accommodation with a direct minimization of the sound field and sensors located near the source of vibration. In this paper attention will be paid to an effective weighting of the near-source sensors in such a way that the interior noise in the vehicle is reduced. Also the nearsource strategy of minimization of the injected power is considered. The latter strategy is theoretically very attractive, but is much more difficult to implement in practice. The techniques are explained and compared to each other with the help of numerical models

Structural basis of the chiral selectivity of Pseudomonas cepacia lipase

To investigate the enantioselectivity of Pseudomonas cepacia lipase, inhibition studies were performed with SC- and RC-(RP,SP)-1,2-dialkylcarbamoylglycero-3-O-p-nitrophenyl alkylphosphonates of different alkyl chain lengths. P. cepacia lipase was most rapidly inactivated by RC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octylphosphonate (RC-trioctyl) with an inactivation half-time of 75 min, while that for the SC-(RP,SP)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octyl-phosphonate (SC-trioctyl) compound was 530 min. X-ray structures were obtained of P. cepacia lipase after reaction with RC-trioctyl to 0.29-nm resolution at pH 4 and covalently modified with RC-(RP,SP)-1,2-dibutylcarbamoylglycero-3-O-p-nitrophenyl butyl-phosphonate (RC-tributyl) to 0.175-nm resolution at pH 8.5. The three-dimensional structures reveal that both triacylglycerol analogues had reacted with the active-site Ser87, forming a covalent complex. The bound phosphorus atom shows the same chirality (SP) in both complexes despite the use of a racemic (RP,SP) mixture at the phosphorus atom of the triacylglycerol analogues. In the structure of RC-tributyl-complexed P. cepacia lipase, the diacylglycerol moiety has been lost due to an aging reaction, and only the butyl phosphonate remains visible in the electron density. In the RC-trioctyl complex the complete inhibitor is clearly defined; it adopts a bent tuning fork conformation. Unambiguously, four binding pockets for the triacylglycerol could be detected: an oxyanion hole and three pockets which accommodate the sn-1, sn-2, and sn-3 fatty acid chains. Van der Waals’ interactions are the main forces that keep the radyl groups of the triacylglycerol analogue in position and, in addition, a hydrogen bond to the carbonyl oxygen of the sn-2 chain contributes to fixing the position of the inhibitor.

Anticancer therapy and apoptosis imaging

Early response prediction is considered an essential tool to obtain a more customized anticancer treatment because it allows for the identification of patients who will benefit most from a particular therapy and prevents the exposure of those patients to toxic, non-effective regimens. Recent discoveries of novel markers in functional imaging have created exciting opportunities for in vivo visualization and quantification of cell death. This review will focus on in vivo apoptosis imaging with various radiotracers as predictive tools for tumor response after anticancer therapy. Particular focus will be on annexin V imaging, a technique with the largest clinical experience to date. This article is part of a Special Issue entitled “Apoptosis: Four Decades Later”

Possible Sources of Bias in Primary Care Electronic Health Record Data Use and Reuse

Background - Enormous amounts of data are recorded routinely in health care as part of the care process, primarily for managing individual patient care. There are significant opportunities to use this data for other purposes, many of which would contribute to establishing a learning health system. This is particularly true for data recorded in primary care settings, as in many countries, these are the first place patients turn to for most health problems. Objective - In this paper, we discuss whether data that is recorded routinely as part of the health care process in primary care is actually fit to use for these other purposes, how the original purpose may affect the extent to which the data is fit for another purpose and the mechanisms behind these effects. In doing so, we want to identify possible sources of bias that are relevant for the (re-)use of this type of data. Methods –This discussion paper is based on the authors’ experience as users of electronic health records data, as a general practitioner, health informatics experts, and health services researchers. It is a product of the discussions they had during the TRANSFoRm project, which was funded by the EU and sought to develop, pilot and evaluate a core information architecture for the Learning Health System (LHS) in Europe, based on primary care electronic health records. Results – We first describe the different stages in the processing of EHR data, as well as the different purposes for which this data is used. Given the different data processing steps and purposes, we then discuss the possible mechanisms for each individual data processing step, that can generate biased outcomes. We identified thirteen possible sources of bias. Four of them are related to the organization of a health care system, some are of a more technical nature. Conclusions - There are a substantial number of possible sources of bias, and very little is known about the size and direction of their impact. However, any (re-)user of data that was recorded as part of the health care process (such as researchers and clinicians) should be aware of the associated data collection process and environmental influences that can affect the quality of the data. Our stepwise, actor and purpose oriented approach may help to identify these possible sources of bias. Unless data quality issues are better understood and unless adequate controls are embedded throughout the data lifecycle, data-driven healthcare will not live up to its expectations. We need a data quality research agenda to devise the appropriate instruments needed to assess the magnitude of each of the possible sources of bias, and then start measuring their impact. The possible sources of bias described in this paper serve as a starting point for this research agenda

Determinants of first-time utilization of long-term care services in the Netherlands:An observational record linkage study

Background: Since in an ageing society more long-term care (LTC) facilities are needed, it is important to understand the main determinants of first-time utilization of (LTC) services. Methods: The Andersen service model, which distinguishes predisposing, enabling and need factors, was used to develop a model for first-time utilization of LTC services among the general population of the Netherlands. We used data on 214,821 persons registered in a database of general practitioners (NIVEL Primary Care Database). For each person the medical history was known, as well as characteristics such as ethnicity, income, home-ownership, and marital status. Utilization data from the national register on long-term care was linked at a personal level. Generalized Linear Models were used to determine the relative importance of factors of incident LTC-service utilization. Results: Top 5 determinants of LTC are need, measured as the presence of chronic diseases, age, household size, household income and homeownership. When controlling for all other determinants, the presence of an additional chronic disease increases the probability of utilizing any LTC service by 45% among the 20+ population (OR = 1.45, 95% CI: 1.41–1.49), and 31% among the 65+ population (OR = 1.31, 95% CI: 1.27–1.36). With respect to the 20+ population, living in social rent (OR = 2.45, 95% CI = 2.25–2.67, ref. = home-owner) had a large impact on utilizing any LTC service. In a lesser degree this was the case for living alone (OR = 1.63, 95% CI = 1.52–1.75, ref. = not living alone). A higher household income was linked with a lower utilization of any LTC service. Conclusions: All three factors of the Anderson model, predisposing, enabling, and need determinants influence the likelihood of future LTC service utilization. This implies that none of these factors can be left out of the analysis of what determines this use. New in our analysis is the focus on incident utilization. This provides a better estimate of the effects of predictors than a prevalence based analysis, as there is less confounding by changes in determinants occurring after LTC initiation. Especially the need of care is a strong factor. A policy implication of this relative importance of health status is therefore that LTC reforms should take health aspects into account. (aut. ref.

The use of out-of-hours primary care during the first year of the COVID-19 pandemic

BACKGROUND: In the Netherlands, General Practitioners (GP) are usually the first point of contact with a health professional for most health problems. Out-of-hours (OOH) primary care is provided by regional OOH services. Changes in consultation rates at OOH services may be regarded as a warning system for failures elsewhere in the healthcare system. Therefore in this study, we investigated how the COVID-19 pandemic changed the use of primary care OOH services during the first year of the pandemic. METHODS: Routine electronic health records data were used from 60% of OOH services in the Netherlands, collected by the Nivel Primary Care Database. We compared consultation rates per week (2020) for COVID-19-like symptoms and other health problems (e.g. small traumas, urinary tract infections), for different age groups, the proportion of remote consultations, and different levels of urgency during the pandemic compared to the same period in 2019. RESULTS: The number of consultations for COVID-19-like symptoms peaked at the start of the COVID-19 pandemic, while consultations for other health problems decreased. These changes in consultation rates differed between age groups. Remote consultations took place more frequently for all health problems, while the proportion of non-urgent health problems increased. CONCLUSION: There were significant changes in the number of consultations and the proportion that were remote for COVID-19-like symptoms and other health problems. Especially care for babies and young children decreased, while the number of consultations for older adults remained stable. The continued use of OOH services by older adults suggests there were unmet care needs elsewhere in our healthcare system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-08096-x

Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity?

INTRODUCTION: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear. METHODS: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1-11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for 67Gallium (67Ga)-transferrin (upper limit of normal 14.1 x 10(-3)/min) was measured. RESULTS: The PLI ranged between 7.5 and 14.0 x 10(-3)/min in the study patients. Two patients received a course of acyclovir and all survived. CONCLUSIONS: The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs

Increased incidence of kidney diseases in general practice after a nationwide albuminuria self-test program

<p>Abstract</p> <p>Background</p> <p>To study the influence of a nationwide albuminuria self-test program on the number of GP contacts for urinary complaints and/or kidney diseases and the number of newly diagnosed patients with kidney diseases by the GP.</p> <p>Methods</p> <p>Data were used from the Netherlands Information Network of General Practice (LINH), including a representative sample of general practices with a dynamic population of approximately 300.000 listed patients. Morbidity data were retrieved from electronic medical records, kept in a representative sample of general practices. The incidence of kidney diseases and urinary complaints before and after the albuminuria self-test program was compared with logistic regression analyses.</p> <p>Results</p> <p>Data were used from 139 general practices, including 444,220 registered patients. The number of GP consultations for kidney diseases and urinary complaints was increased in the year after the albuminuria self-test program and particularly shortly after the start of the program. Compared with the period before the self-test program, more patients have been diagnosed by the GP with symptoms/complaints of kidney disease and urinary diseases (OR = 1.7 (CI 1.4 - 2.0) and OR = 2.1 (CI 1.9 - 2.3), respectively). The odds on an abnormal urine-test in the period after the self-test program was three times higher than the year before (OR = 3.0 (CI 2.4 - 3.6)). The effect of the self-test program on newly diagnosed patients with an abnormal urine test was modified by both the presence of the risk factors hypertension and diabetes mellitus. For this diagnosis the highest OR was found in patients without both conditions (OR = 4.2 (CI 3.3 - 5.4)).</p> <p>Conclusions</p> <p>A nationwide albuminuria self-test program resulted in an increasing number of newly diagnosed kidney complaints and diseases the year after the program. The highest risks were found in patients without risk factors for kidney diseases.</p

Function of the fully conserved residues Asp99, Tyr52 and Tyr73 in phospholipase A2

In the active centre of pancreatic phospholipase A2 His48 is at hydrogen-bonding distance to Asp99. This Asp-His couple is assumed to act together with a water molecule as a catalytic triad. Asp99 is also linked via an extended hydrogen bonding system to the side chains of Tyr52 and Tyr73. To probe the function of the fully conserved Asp99, Tyr52 and Tyr73 residues in phospholipase A2, the Asp99 residue was replaced by Asn, and each of the two tyrosines was separately replaced by either a Phe or a Gln. The catalytic and binding properties of the Phe52 and Phe73 mutants did not change significantly relative to the wild-type enzyme. This rules out the possibility that either one of the two Tyr residues in the wild-type enzyme can function as an acyl acceptor or proton donor in catalysis. The Gln73 mutant could not be obtained in any significant amounts probably due to incorrect folding. The Gln52 mutant was isolated in low yield. This mutant showed a large decrease in catalytic activity while its substrate binding was nearly unchanged. The results suggest a structural role rather than a catalytic function of Tyr52 and Tyr73. Substitution of asparagine for aspartate hardly affects the binding constants for both monomeric and micellar substrate analogues. Kinetic characterization revealed that the Asn99 mutant has retained no less than 65% of its enzymatic activity on the monomeric substrate rac 1,2-dihexanoyldithio-propyl-3-phosphocholine, probably due to the fact that during hydrolysis of monomeric substrate by phospholipase A2 proton transfer is not the rate-limiting step. The Asp to Asn substitution decreases the catalytic rate on micellar 1,2-dioctanoyl-sn-glycero-3-phosphocholine 25-fold. To explain this remaining activity we suggest that in the mutant the Asn99 orients His48 in the same way as Asp99 orients His48 in native phospholipase A2 and that the lowered activity is caused by a reduced stabilization of the transition state

Inter-practice variation in diagnosing hypertension and diabetes mellitus: a cross-sectional study in general practice

BACKGROUND: Previous studies of inter-practice variation of the prevalence of hypertension and diabetes mellitus showed wide variations between practices. However, in these studies inter-practice variation was calculated without controlling for clustering of patients within practices and without adjusting for patient and practice characteristics. Therefore, in the present study inter-practice variation of diagnosed hypertension and diabetes mellitus prevalence rates was calculated by 1) using a multi-level design and 2) adjusting for patient and practice characteristics. METHODS: Data were used from the Netherlands Information Network of General Practice (LINH) in 2004. Of all 168.045 registered patients, the presence of hypertension, diabetes mellitus and all available ICPC coded symptoms and diseases related to hypertension and diabetes, were determined. Also, the characteristics of practices were used in the analyses. Multilevel logistic regression analyses were performed. RESULTS: The 95% prevalence range for the practices for the prevalence of diagnosed hypertension and diabetes mellitus was 66.3 to 181.7 per 1000 patients and 22.2 to 65.8 per 1000 patients, respectively, after adjustment for patient and practice characteristics. The presence of hypertension and diabetes was best predicted by patient characteristics. The most important predictors of hypertension were obesity (OR = 3.5), presence of a lipid disorder (OR = 3.0), and diabetes mellitus (OR = 2.6), whereas the presence of diabetes mellitus was particularly predicted by retinopathy (OR = 8.5), lipid disorders (OR = 2.8) and hypertension (OR = 2.7). CONCLUSION: Although not the optimal case-mix could be used in this study, we conclude that even after adjustment for patient (demographic variables and risk factors for hypertension and diabetes mellitus) and practice characteristics (practice size and presence of a practice nurse), there is a wide difference between general practices in the prevalence rates of diagnosed hypertension and diabetes mellitu