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With increasing digitalization, manufacturing systems provide data to describe their current condition, allowing for a digital representation of the physical system. This enables a transition to more efficient maintenance and production planning approaches. In this context, selecting suitable prognostic methods is crucial and requires a high level of expertise and domain knowledge. This paper proposes a conceptional model for an integrated approach to solve these problems that are usually treated separately. Following an introduction of enablers for advanced maintenance strategies and prognostic methods, the conceptional model is presented. Concurrently, the state of the research of the modules is outlined. To conclude, open research questions are summarized.

Prognostic methods for predictive maintenance have been presented extensively in the literature. While this area’s continuing effort positively affects individual predictive maintenance solutions’ performance and capabilities, a method’s setup remains a big hurdle as the solution space is becoming more complex. The critical settings of a prognostic method are the selection of suitable modeling techniques used for behavior- and condition-modeling, as well as a forecast model for failure prediction. This paper presents a generalized topology of a prognostic method to ease the design of maintenance systems and allow for quicker individual method design and modification. After a broad literature review, the topology and its base components are presented, and an overview of the different kinds of models related to predictive maintenance applications is given.

In the Netherlands, older cyclists run an increased risk of bicycle crashes. Critical factors are low-speed interactions, stopping, (dis)mounting, and potentially misjudging riding speeds. A Bicycle Light Communication System (BLCS) was therefore developed that displayed riding speed, braking, and turning intentions. In an experiment, 21 older and 20 younger cyclists observed BLCS-signals of a lead cyclist and estimated speeds of an approaching cyclist, with and without BLCS. Interviews were conducted to assess general opinions on BLCS and its influence on cycling behaviour. In a small follow-up study, twelve older cyclists used a BLCS-bicycle one week to explore first user-impressions. The majority evaluated the BLCS positively, mainly the turning indicator and brake light components, even though interpreting the speed signals was difficult. Although the first user-impressions revealed that the direction indicator does not influence self-reported balance (positively or negatively), the majority reported that they would like to use a BLCS themselves.

Thermodynamic quantities of small systems fluctuate and have to be characterised by their appropriate probability distributions. Within the two-point energy measurement prescription, the distribution of work in a quantum system can be derived from the transition probability from initial to final energy. We consider a simple yet representative model system starting in thermodynamic equilibrium and driven by an external force, and compare two different numerical techniques to determine this transition probability with respect to accuracy and numerical effort. In addition, we perform a semi-classical analysis of the process using the WKB approximation. The results agree well with the numerically exact values if Airy-tails modelling the tunnelling into classically forbidden regions of phase space are properly taken into account.

SummaryWe present a fun alternative geometric approach for computing the volume of a “box” in spherical coordinates, which we then use to explain the formula for spherical triple integrals. Each step of our approach works well as an interactive classroom exercise.

IMPORTANCE: Levetiracetam is a commonly used antiepileptic drug, yet psychiatric adverse effects are common and may lead to treatment discontinuation. OBJECTIVE: To derive prediction models to estimate the risk of psychiatric adverse effects from levetiracetam use. DESIGN, SETTING, AND PARTICIPANTS: Retrospective open cohort study. All patients meeting the case definition for epilepsy after the Acceptable Mortality Reporting date in The Health Improvement Network (THIN) database based in the United Kingdom (inclusive January 1, 2000, to May 31, 2012) who received a first-ever prescription for levetiracetam were included. Of 11 194 182 patients registered in THIN, this study identified 7400 presumed incident cases (66.1 cases per 100 000 persons) over a maximum of 12 years’ follow-up. The index date was when patients received their first prescription code for levetiracetam, and follow-up lasted 2 years or until an event, loss to follow-up, or censoring. The analyses were performed on April 22, 2018. EXPOSURE: A presumed first-ever prescription for levetiracetam. MAIN OUTCOMES AND MEASURES: The outcome of interest was a Read code for any psychiatric sign, symptom, or disorder as reached through consensus by 2 authors. This study used regression techniques to derive 2 prediction models, one for the overall population and one for those without a history of a psychiatric sign, symptom, or disorder during the study period. RESULTS: Among 1173 patients with epilepsy receiving levetiracetam, the overall median age was 39 (interquartile range, 25-56) years, and 590 (50.3%) were female. A total of 14.1% (165 of 1173) experienced a psychiatric symptom or disorder within 2 years of index prescription. The odds of reporting a psychiatric symptom were significantly elevated for women (odds ratio [OR], 1.41; 95% CI, 0.99-2.01; P = .05) and those with a preexposure history of higher social deprivation (OR, 1.15; 95% CI, 1.01-1.31; P = .03), depression (OR, 2.20; 95% CI, 1.49-3.24; P < .001), anxiety (OR, 1.74; 95% CI, 1.11-2.72; P = .02), or recreational drug use (OR, 2.02; 95% CI, 1.20-3.37; P = .008). The model performed well after stratified k = 5-fold cross-validation (area under the curve [AUC], 0.68; 95% CI, 0.58-0.79). There was a gradient in risk, with probabilities increasing from 8% for 0 risk factors to 11% to 17% for 1, 17% to 31% for 2, 30% to 42% for 3, and 49% when all risk factors were present. For those free of a preexposure psychiatric code, a second model performed comparably well after k = 5-fold cross-validation (AUC, 0.72; 95% CI, 0.54-0.90). Specificity was maximized using threshold cutoffs of 0.10 (full model) and 0.14 (second model); a score below these thresholds indicates safety of prescription. CONCLUSIONS AND RELEVANCE: This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam. These algorithms can be used to guide prescription in clinical practice.

Control over the frequency and pattern of neuronal spike discharge depends on Ca2+-gated K+channels that reduce cell excitability by hyperpolarizing the membrane potential. The Ca2+-dependent slow afterhyperpolarization (sAHP) is one of the most prominent inhibitory responses in the brain, with sAHP amplitude linked to a host of circuit and behavioural functions. Yet the channel that underlies the sAHP has defied identification for decades. Here we show that intermediate conductance Ca2+-dependent K+(IKCa) channels underlie the sAHP generated by trains of synaptic input or postsynaptic stimuli in CA1 hippocampal pyramidal cells. These findings are significant in providing a molecular identity for the sAHP of central neurons that will identify pharmacological tools capable of potentially modifying the several behavioural or disease states associated with the sAHP.

The older cyclist is more prone to get cycling accidents than younger cyclists. To support the older cyclist, a rear- and front-view assistant were developed that warns the cyclist of approaching traffic. User tests to evaluate system performance, user-experience and effects on behaviour were performed with 20 older cyclists (>64 years) on a predefined route outdoors with and without support from both assistants. During this route, the cyclist was confronted with two controlled scenarios with an overtaking and an oncoming cyclist. The participants' cycling behaviour was assessed by measuring lateral distance to the other cyclist, and distance maintained to the verge. The assistants had no effect on experienced mental workload. Both assistants received positive evaluations, although the rear-view assistant was experienced as more useful. Using the front-view assistant resulted in less lateral distance to the approaching oncoming cyclist, while the use of the rear-view assistant did not have effects on lateral distance.

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ABSTRACTOur previous work reported that KCa3.1 (IKCa) channels are expressed in CA1 hippocampal pyramidal cells and contribute to the slow afterhyperpolarization that regulates spike accommodation in these cells. The current report presents data from single cell RT-PCR that further reveals mRNA in CA1 cells that corresponds to the sequence of an IKCa channel from transmembrane segments 5 through 6 including the pore region, revealing the established binding sites for 4 different IKCa channel blockers. A comparison of methods to internally apply the IKCa channel blocker TRAM-34 shows that including the drug in an electrode from the onset of an experiment is unviable given the speed of drug action upon gaining access for whole-cell recordings. Together the data firmly establish IKCa channel expression in CA1 neurons and clarify methodological requirements to obtain a block of IKCa channel activity through internal application of TRAM-34.

Defossilizing ethylene production to decrease CO2emissions is an integral challenge in the context of climate change, as ethylene is one of the most important bulk chemicals. Electrochemical CO2reduction is a promising alternative to conventional steam cracking, reducing the carbon footprint of ethylene production when coupled with renewable energy sources. In this work, we present the optimization of a boron-doped copper catalyst towards higher selectivity for ethylene. The method for catalyst preparation is optimized, obtaining larger batch sizes while maintaining high ethylene selectivity. Additionally, life cycle assessment is applied to investigate the environmental impacts of electrochemical CO2reduction and to compare its carbon footprint with alternative pathways for ethylene production. Altogether, the scaled-up catalyst achieves promising electrochemical results while significantly reducing the carbon footprint for ethylene production in comparison to the conventional production pathway when combined with low-emission energy.

The aim of this study was to evaluate the effects on behaviour, mental effort and acceptance of a simple prototype of an electronic rear-view assistance system designed for older cyclists that are at risk of falls. The prototype was incorporated into a simple cycling simulator and provided information about traffic from behind in two modalities: visual and haptic. Twenty-one older participants (>64 years) completed three conditions: warnings in two modalities and a control condition without warnings. Mental effort and acceptance were assessed using subjective rating scales and by monitoring changes in cycling speed. Less mental effort was reported when using the rear-view assistant. Significantly more correct decisions regarding a safe left turn were made with system advice. No significant speed differences were found between the two modality conditions. It is concluded that the electronic rear-view assistance system can potentially support the older cyclist successfully by warning for traffic coming from behind.

Mutual learning is a fundamental element in transdisciplinary (Td) sustainability research. It allows for integrating knowledge and experiences gained in different contexts, including the building of consensus about necessary transformations to reach sustainability solutions. To successfully achieve mutual learning, appropriate conditions are required. These range from providing boundary objects that serve knowledge integration, the development of a common language and knowledge, and shared experiences to transparency concerning the objectives and motives of all those involved. Mutual learning is particularly challenging from an intercultural perspective in both local and global processes. Interaction among the participants is based on experiential, educational, and cultural dimensions that induce different types of knowledge and cognition, thought styles, socializations, constraints and preferences in socio-political structures and day-to-day practices. In this article, formats of case-basedMutual Learning Sessions (cbMLS) that organize mutual learning based on a single case or a set of cases are presented. The different formats have been developed and studied in the context of a global Td process on phosphorus management (i.e., the Global TraPs project). After presenting the formats of cbMLS, the paper presents the first results from an empirical, integrated qualitative study based on interviews and observations, and discusses potentials and limitations of cbMLS, in particular their application in an international context. We further highlight challenges and learning experiences that have to be met in Td mutual learning processes.

Venous thrombosis is common in the older population. Assessment of risk factors is necessary to implement preventive measures.

During tissue retraction with a laparoscopic grasper, tissue-damaging pressures can occur. Past research suggests that peak pressures can be considerably reduced by rounding the edges or covering the tip of the end effector with a silicon sleeve. To identify grasping methods that limit tissue damage, the effects of (a) Young’s modulus of the end effector, (b) curvature of the end effector, and (c) angle with which the tissue is pulled relative to the plane of the end effector, on the pressure generated on the tissue were investigated. Artificial skin was placed between two non-serrated jaws, a pressure-sensitive film was interposed between the skin and upper jaw, and the end effector was loaded with 13 N. End effectors with Young’s moduli of 0.09, 0.67, 1.49 MPa, and 69 GPa, and with non-rounded and 5 mm rounded edges were tested under pulling angles of 25°, 50°, and 75°. For non-rounded end effectors, the maximum pressure and the area across which pressure exceeded the safety threshold for tissue damage increased with Young’s modulus and pulling angle. For rounded end effectors, maximum pressure did not increase monotonically with Young’s modulus. Instead, the end effector with the second lowest Young’s modulus yielded significantly lower maximum pressure than the end effector with the lowest Young’s modulus. For rounded end effectors, pressures were below the safety threshold for all Young’s moduli. This indicates that to prevent tissue damage, soft graspers may not be needed; rounding the edges of metal graspers could suffice for preventing tissue damage.

High voltage-activated (HVA) Cav channels form complexes with KCa1.1 channels, allowing reliable activation of KCa1.1 current through a nanodomain interaction. We recently found that low voltage-activated Cav3 calcium channels also create KCa1.1-Cav3 complexes. While coimmunoprecipitation studies again supported a nanodomain interaction, the sensitivity to calcium chelating agents was instead consistent with a microdomain interaction. A computational model of the KCa1.1-Cav3 complex suggested that multiple Cav3 channels were necessary to activate KCa1.1 channels, potentially causing the KCa1.1-Cav3 complex to be more susceptible to calcium chelators. Here, we expanded the model and compared it to a KCa1.1-Cav2.2 model to examine the role of Cav channel conductance and kinetics on KCa1.1 activation. As found for direct recordings, the voltage-dependent and kinetic properties of Cav3 channels were reflected in the activation of KCa1.1 current, including transient activation from lower voltages than other KCa1.1-Cav complexes. Substantial activation of KCa1.1 channels required the concerted activity of several Cav3.2 channels. Combined with the effect of EGTA, these results suggest that the Ca2+domains of several KCa1.1-Cav3 complexes need to cooperate to generate sufficient [Ca2+]i, despite the physical association between KCa1.1 and Cav3 channels. By comparison, Cav2.2 channels were twice as effective at activating KCa1.1 channels and a single KCa1.1-Cav2.2 complex would be self-sufficient. However, even though Cav3 channels generate small, transient currents, the regulation of KCa1.1 activity by Cav3 channels is possible if multiple complexes cooperate through microdomain interactions.

The synthesis of an azide containing PNA monomer is described. The monomer was incorporated into two PNA sequences for the purpose of synthesizing an intercalating fluorophore-labeled PNA and a metal binding hairpin using a solid phase copper catalyzed azide-alkyne Huisgen cycloaddition (CuAAC). Click chemistry was performed using 2-ethynylfluorene or 1-ethynylpyrene to add a fluorophore to the PNA, which were tested for their ability to recognize an abasic site on a DNA target. A PNA hairpin possessing azide monomers at each termini was synthesized and reacted with 2-ethynylpyridine to form a hairpin that is stabilized by Ni2+.

Photographs of several puppets at the Halloween marionette shows called "Driveway Follies" by Larry Schmidt are presented including a zombie showgirl, witch doctor, and Hercules.

The incidence of venous thrombosis (VT) increases sharply with age: it is very rare in young individuals (< 1 per 10 000 per year) but increases to ∼ 1% per year in the elderly, which indicates that aging is one of the strongest and most prevalent risk factor for venous thrombosis. The cause of this steep age gradient is as yet, unexplained. The aim of this review was to provide an overview of studies on the effect of conventional risk factors as well as age‐specific risk factors for thrombosis in the elderly. Limited data are available on risk factors for thrombosis in the elderly, i.e. all results are based on small study groups. Results indicate that, of the conventional risk factors, malignant disease, the presence of co‐morbidities and the genetic risk factors factor (F)V Leiden and the prothrombin mutation seem to be associated with an increased risk of venous thrombosis. In the elderly, the population attributable risk (PAR) of malignancy is approximately 35%, for co‐morbidities a PAR up to 25% is found, and the contribution of genetic risk factors to the thrombosis incidence is estimated to be 7–22%. Age‐specific risk factors of thrombosis, i.e. endothelial dysfunction and frailty may be important in the explanation of the increased incidence of VT in the elderly. In conclusion, as aging is a major risk factor for thrombosis, further identification of the risk factors for thrombosis in the elderly is needed to elucidate the age gradient of the incidence of VT and to target preventive measures.

SummaryIn the same vein as a Classroom Capsule of Arnold Insel on the arctangent, we present a direct geometric derivation of the integral formulae for the inverse hyperbolic functions. We then use these formulae to obtain the derivatives of the various hyperbolic trigonometric functions.

The South Atlantic Anomaly (SAA) is an area of geomagnetic weakness that represents the most significant anomaly in the present‐day field. Notwithstanding anomalies such as these, a long‐lived hypothesis is that, if averaged over sufficient time (104–106years), the Earth's magnetic field approximates a geocentric axial dipole (GAD). The question of how significant the non‐GAD features are in the time‐averaged field is an important and unresolved one. The SAA has not always been visible in the historic and paleo‐field models; yet an unstable field was reported in the South Atlantic region on a multimillion‐year timescale. This study presents the first paleointensity study from Saint Helena, a volcanic island in the South Atlantic consisting primarily of lavas emplaced between 10 and 8 Ma. While paleointensity success rates were low, we were able to recover results from five independent lavas that together suggest a low field intensity of 10.5 ± 3.0 μT corresponding to a virtual axial dipole moment (VADM) of 2.4 ± 0.7 × 1022A m2. These low paleointensity estimates suggest a field in the South Atlantic that was not only unstable in directions, but also substantially weaker than expected. We consider this to constitute further evidence that the SAA is not a single occurrence but rather, the latest in a series of recurring weaknesses in the field in this region, probably caused by Reversed Flux Patches on the Core Mantle Boundary. The Earth's magnetic field is created by liquid iron convecting within the outer core. This field is highly variable. In the South Atlantic region, there is a large patch where the field is less strong than expected, causing us and our technology to be less protected against solar radiation. In that region lies Saint Helena, a volcanic island from which we collected samples that we used for paleomagnetic analysis. We performed experiments to derive the intensity of the field at that location when the rocks formed, which was 10–8 million years ago. Our results show that the magnetic field of Saint Helena was very weak during that interval suggesting that the modern irregular weak patch has been a recurring irregularity on a multimillion‐year timescale. This suggests that the weakness is most likely linked to heterogeneities in the lowermost mantle, which interfere with convective flow in the outer core. The first paleointensity results from Saint Helena suggest a low field in the South Atlantic between 10 and 8 MaLow paleointensity estimates provide further support of recurring anomalous behavior caused by reverse flux patches under AfricaResults from successful Ar/Ar experiments show that the Saint Helena volcanoes were active between 10 and 8 Ma The first paleointensity results from Saint Helena suggest a low field in the South Atlantic between 10 and 8 Ma Low paleointensity estimates provide further support of recurring anomalous behavior caused by reverse flux patches under Africa Results from successful Ar/Ar experiments show that the Saint Helena volcanoes were active between 10 and 8 Ma