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Abstract Background Congenital heart disease (CHD) is the most common congenital anomaly. Almost 90% of isolated cases have an unexplained genetic etiology after clinical testing. Non-canonical splice variants that disrupt mRNA splicing through the loss or creation of exon boundaries are not routinely captured and/or evaluated by standard clinical genetic tests. Recent computational algorithms such as SpliceAI have shown an ability to predict such variants, but are not specific to cardiac-expressed genes and transcriptional isoforms. Methods We used genome sequencing (GS) (n = 1101 CHD probands) and myocardial RNA-Sequencing (RNA-Seq) (n = 154 CHD and n = 43 cardiomyopathy probands) to identify and validate splice disrupting variants, and to develop a heart-specific model for canonical and non-canonical splice variants that can be applied to patients with CHD and cardiomyopathy. Two thousand five hundred seventy GS samples from the Medical Genome Reference Bank were analyzed as healthy controls. Results Of 8583 rare DNA splice-disrupting variants initially identified using SpliceAI, 100 were associated with altered splice junctions in the corresponding patient myocardium affecting 95 genes. Using strength of myocardial gene expression and genome-wide DNA variant features that were confirmed to affect splicing in myocardial RNA, we trained a machine learning model for predicting cardiac-specific splice-disrupting variants (AUC 0.86 on internal validation). In a validation set of 48 CHD probands, the cardiac-specific model outperformed a SpliceAI model alone (AUC 0.94 vs 0.67 respectively). Application of this model to an additional 947 CHD probands with only GS data identified 1% patients with canonical and 11% patients with non-canonical splice-disrupting variants in CHD genes. Forty-nine percent of predicted splice-disrupting variants were intronic and > 10 bp from existing splice junctions. The burden of high-confidence splice-disrupting variants in CHD genes was 1.28-fold higher in CHD cases compared with healthy controls. Conclusions A new cardiac-specific in silico model was developed using complementary GS and RNA-Seq data that improved genetic yield by identifying a significant burden of non-canonical splice variants associated with CHD that would not be detectable through panel or exome sequencing.

Within the healthcare system, identification and intervention for intimate partner violence (IPV) are critical, yet often hindered by siloed operations among healthcare workers. Effective interprofessional collaboration is pivotal for timely and appropriate interventions. This article describes an interprofessional educational simulation involving nursing and social work students. Pairs engaged in risk assessment and safety planning for IPV. In the pilot run with 140 nursing and 137 social work students, post-simulation results increased confidence (t = 5.25, p = 0.001) and positive evaluation of IPV knowledge (t = 63.22, p = 0.001). Focus groups underscored team synergy, communication skills, and prior experiences as critical elements. Future projects should expand simulation scopes to address diverse situations and include additional professions interacting with survivors.

Industry 4.0 drives the demand for cost-efficient and reliable process data and condition monitoring. Therefore, visualizing the state of tribological contacts becomes important, as they are regularly found in the center of many applications. Utilizing rolling element bearings as sensors and monitoring their health by the electrical impedance method are promising approaches as it allows, e.g., load sensing and detection of bearing failures. The impedance cannot be measured directly, but there are various methods available. This paper discusses advantages and disadvantages and suggests the AC Wheatstone bridge as a reliable way of measuring impedances with low phase angles at sampling rates in the kHz range. The corresponding equations are introduced, a simulation built, an uncertainty mode and effects analysis carried out and sample measurement results of real rolling elements shown. It can be demonstrated that the AC Wheatstone bridge meets the proposed requirements for sensory utilization and condition monitoring when the bearing is operated in the hydrodynamic regime.

Condition monitoring of machine elements becomes more important over the last years. Different approaches to detect failures in mechanical components have been developed. All these methods are located at a distance from the point of interest, the observed machine element. This leads to uncertainties in the data, which influences the data quality negatively. Using the electrical impedance for condition monitoring enables in situ measurement with reduced uncertainties and higher data quality. In the last years, research considering this topic was done, but a systematic overview is missing. In this article, a systematic literature research according to the PRISMA approach is fulfilled. The main questions are, what application fields for electrical impedance-based condition monitoring approaches exists and which research gaps are not addressed yet. At the end, 21 articles are categorized in their application fields. Analyzing their content, research questions are identified which have to be addressed in further investigations.

We report a case of a 74-year-old female with a history of a prosthetic joint infection that was successfully treated with a single-stage exchange arthroplasty, off antibiotics, and without symptoms for 20 months. She presented 1 week after a cat scratch with acute knee pain, and aspiration grew Pasteurella multocida. She was successfully treated with surgical debridement and a prolonged course of antibiotics. Debate remains in the literature regarding whether recurrent infections represent a previously undetected organism or a new infection. Our report provides convincing evidence that, at least in some circumstances, the infection is new. Furthermore, this is the first case described of P. multocida resulting in a recurrent prosthetic joint infection after a previously successful exchange arthroplasty due to a different causative organism.

Abstract FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-β1, TNF-α, IL1α, and IL1β were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.

Background Physical therapy (PT) plays an important role in the recovery of function following anatomic total shoulder arthroplasty (aTSA). While several PT protocols have been published for these patients, there is no standardized protocol for aTSA rehabilitation. This lack of standardization may lead to confusion between patients and physicians, possibly resulting in suboptimal outcomes. This study examines how PT protocols provided by academic orthopedic surgery programs vary regarding therapeutic goals and activities following aTSA. Methods PT protocols for aTSA available online from the Accreditation Council for Graduate Medical Education accredited orthopedic surgery programs were included for review. Each protocol was analyzed to evaluate it for differences in recommendation of length of immobilization, range of motion (ROM) goals, start time for and progression of therapeutic exercises, and timing for return to functional activity. Results Of 175 accredited programs, 25 (14.2%) had protocols publicly available, programs (92%) recommended sling immobilization outside of therapy for an average of 4.4±2.0 weeks. Most protocols gave recommendations on starting active forward flexion (24 protocols, range 1–7 weeks), external rotation (22 protocols, range 1–7 weeks), and internal rotation (18 protocols, range 4–7 weeks). Full passive ROM was recommended at 10.8±5.7 weeks, and active ROM was 13.3±3.9 weeks, on average. ROM goals were inconsistent among protocols, with significant variations in recommended ROM and resistance exercise start times. Only 13 protocols (52%) gave recommendations on resuming recreational activities (mean, 17.4±4.4 weeks). Conclusions Publicly available PT protocols for aTSA rehabilitation are highly variable. Level of evidenceLevel IV.

The opportunities of impedance-based condition monitoring for rolling bearings have been shown earlier by the authors: Changes in the impedance signal and the derived features enable the detection of pitting damages. Localizing and measuring the pitting length in the raceway direction is possible. Furthermore, the changes in features behavior are physically explainable. These investigations were focused on a single bearing type and only one load condition. Different bearing types and load angles were not considered yet. Thus, the impedance signals and their features of different bearing types under different load angles are investigated and compared. The signals are generated in fatigue tests on a rolling bearing test rig with conventional integrated vibration analysis based on structural borne sound. The rolling bearing impedance is gauged using an alternating current measurement bridge. Significant changes in the vibration signals mark the end of the fatigue tests. Therefore, comparing the response time of the impedance can be compared to the vibration signal response time. It can be shown that the rolling bearing impedance is an instrument for condition monitoring, independently from the bearing type. In case of pure radial loads, explicit changes in the impedance signal are detectable, which indicate a pitting damage. Under combined loads, the signal changes are detectable as well, but not as significant as under radial load. Damage-indicating signal changes occur later compared to pure radial loads, but nevertheless enable an early detection. Therefore, the rolling bearing impedance is an instrument for pitting damage detection, independently from bearing type and load angle.

Background: The traditional lateral extensile approach to the calcaneus allows for excellent visualization but is associated with high wound complication rates. The sinus tarsi approach has been shown to produce similar radiographic outcomes with much lower rates of wound complications. The purpose of this study is to prospectively determine clinical and radiographic outcomes in calcaneus fractures treated with a sinus tarsi approach. Methods: Twenty-nine patients with 30 calcaneus fractures underwent operative fixation through a sinus tarsi approach and were prospectively evaluated. Routine pre- and postoperative radiographs were obtained, in addition to computed tomography (CT) scans at 6 weeks and 12 months after surgery. Patient-reported outcomes including American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analog scale (VAS) pain score, Veterans Rand 12-Item Health Survey (VR-12), and Foot Functional Index (FFI) were recorded. Patients were followed for a minimum of 1 year postoperation. Results: Twenty-one patients with 22 calcaneus fractures completed 1 year of follow-up. At 12 months postoperation, 20 of 22 patients (91%) had 0 to 2 mm of fracture displacement at the posterior facet on CT scans whereas 2 of 22 patients had 2 to 4 mm of fracture displacement. There was no significant change in posterior facet fracture displacement comparing 6-week and 12-month postoperative CT scans ( P > .99). Mean postoperative Bohler angle was 26.1 degrees compared to 13.2 degrees preoperatively. All patients had complete union of fracture site. There were no major wound complications. Four of 22 patients (18.2%) had minor wound complications. AOFAS, FFI, and VAS pain scores improved postoperatively but were not found to correlate with Bohler angle or critical angle of Gissane. Conclusion: We found that in select patients excellent anatomic alignment and good clinical outcomes with low wound complication rates can be achieved when fixing calcaneus fractures through the sinus tarsi approach. Level of Evidence: Level II, prospective cohort study.

Currently, therapeutic and diagnostic applications of antibodies are primarily limited to cell surface-exposed and extracellular proteins. However, research has been conducted on cell-penetrating peptides (CPP), as well as cytosol-penetrating antibodies, to overcome these limitations. In this context, a heparin sulfate proteoglycan (HSPG)-binding antibody was serendipitously discovered, which eventually localizes to the cytosol of target cells. Functional characterization revealed that the tested antibody has beneficial cytosol-penetrating capabilities and can deliver cargo proteins (up to 70 kDa) to the cytosol. To achieve tumor-specific cell targeting and cargo delivery through conditional activation of the cell-penetrating antibody in the tumor microenvironment, a single-chain Fc fragment (scFv) and a VL domain were isolated as masking units. Several in vitro assays demonstrated that fusing the masking protein with a cleavable linker to the cell penetration antibody results in the inactivation of antibody cell binding and internalization. Removal of the mask via MMP-9 protease cleavage, a protease that is frequently overexpressed in the tumor microenvironment (TME), led to complete regeneration of binding and cytosol-penetrating capabilities. Masked and conditionally activated cytosol-penetrating antibodies have the potential to serve as a modular platform for delivering protein cargoes addressing intracellular targets in tumor cells.

In recent years, electrical damage phenomena in rolling and plain bearings have become increasingly important due to the growing electrification of individual mobility and renewable energy technologies [...]

The last several years have seen intense debate about the issue of transitioning between standard and daylight saving time. In the United States, the annual advance to daylight saving time in spring, and fall back to standard time in autumn, is required by law (although some exceptions are allowed under the statute). An abundance of accumulated evidence indicates that the acute transition from standard time to daylight saving time incurs significant public health and safety risks, including increased risk of adverse cardiovascular events, mood disorders, and motor vehicle crashes. Although chronic effects of remaining in daylight saving time year-round have not been well studied, daylight saving time is less aligned with human circadian biology-which, due to the impacts of the delayed natural light/dark cycle on human activity, could result in circadian misalignment, which has been associated in some studies with increased cardiovascular disease risk, metabolic syndrome and other health risks. It is, therefore, the position of the American Academy of Sleep Medicine that these seasonal time changes should be abolished in favor of a fixed, national, year-round standard time.

The UN sustainable development goals (SDGs) and the Paris climate target require a holistic transformation towards human well-being within planetary boundaries. However, there are growing debates on how to best pursue these targets. Proposed transformation strategies include market- and technology-driven green-growth, shifting towards a sufficiency-oriented post-growth economy, and a transformation driven primarily by strong government action. Here we quantify three alternative sustainable development pathways (SDPs), Economy-driven Innovation, Resilient Communities, and Managing the Global Commons, that reflect these different societal strategies. We compare the quantifications from two integrated assessment models and two sectoral models of the buildings and materials sectors across a broad set of indicators for sustainable development and climate action. Our global multi-scenario and multi-model analysis shows that all three SDPs enable substantial progress towards the human development goals of the SDGs. They simultaneously limit global warming and prevent further environmental degradation, with the sufficiency-oriented Resilient Communities scenario showing the lowest peak warming and lowest reliance on carbon dioxide removal as well as the largest improvements in biodiversity intactness. The SDPs also alleviate the concerns about the biogeophysical and technological feasibility of narrowly-focused climate change mitigation scenarios. However, the shifts in energy and food consumption patterns assumed in the SDPs, ranging from moderate in Economy-driven Innovation to very ambitious in Resilient Communities, also lead to increased challenges regarding socio-cultural feasibility.

Category: Trauma; Midfoot/Forefoot Introduction/ Purpose: Primary arthrodesis of Lisfranc and midfoot fracture-dislocations is a reliable treatment option, yet concerns remain about nonunion and dorsiflexion malunion. The use of a new generation of nitinol staples has proliferated in midfoot arthrodesis. The purpose of this study is to examine the use of nitinol staples in primary arthrodesis of acute Lisfranc fracture-dislocations, comparing outcomes to traditional plate and screw fixation. The primary hypothesis is that nonunion rates are lower with constructs that include nitinol staples than those with plates and screws alone. Secondary hypotheses are: 1. Total operative and tourniquet time are shorter using nitinol staples. 2. Reoperation rates are lower using nitinol staples. 3. Dorsiflexion malunion rates are lower using nitinol staples. 4. Functional outcome scores will indicate comparable post-arthrodesis disability. Methods: Midfoot fracture-dislocations treated with primary arthrodesis by seven foot and ankle orthopaedic surgeons at a tertiary referral center from 1/1/2012 to 8/1/2021 were reviewed. Patients with open fractures, fractures managed with external fixation, Charcot arthropathy, neuropathy, previous midfoot surgery, or concomitant hindfoot/ankle fractures were excluded. Of 160 eligible patients, 121 patients met the required 4-month minimum radiographic follow-up. Preoperative records were reviewed, evaluating for associated metatarsal and cuneiform fractures, operative and tourniquet time, joints included, and fixation construct. Outcomes were analyzed at both patient and individual joint levels. Patients (121 total) and individual joints (305 total) were categorized as either staples alone (45 patients, 154 joints), staples plus plates and screws (hybrid) (45 patients, 40 joints), or plates and screws alone (31 patients, 111 joints). Postoperative radiographs were analyzed for union and malunion at each joint fused. Medical records were reviewed for postoperative complications. FAAM, VR-12, and NPRS were collected. Results: When assessed at the individual joint level, the nonunion rate was higher (8.1%, 9/111) among joints fixed with plate and screw constructs than with hybrid (2.5%, 1/40) or staple only constructs (1.3%, 2/154) (P = 0.017). Of the 12 nonunions in the study, 6 had either a metatarsal or cuneiform fracture. Median OR and tourniquet time were both shorter for hybrid (92 & 83 minutes) and staple only (67 & 63 minutes) constructs compared to plate and screw only fixation (106 & 95 minutes) (P = 0.0003 & < 0.0001). There were 15 (12.4%) reoperations including 10 hardware removals, 3 nonunion revisions, and 1 malunion revision. There was no difference in reoperation, malunion (14 total, 11.6%), or patient reported outcome measure between fixation types. Conclusion: Nitinol staples are effective in achieving bony fusion when used alone or in combination with plates and screws. Their use should be considered for primary arthrodesis of Lisfranc and midfoot fracture-dislocations due to lower rates of nonunion and shorter tourniquet and operative time compared to traditional plate and screw fixation. Further studies are needed to determine if staples decrease the risk for dorsiflexion malunion and improve patient reported outcomes.

Abstract Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.

Category: Trauma; Midfoot/Forefoot Introduction/Purpose: Primary arthrodesis of Lisfranc and midfoot fracture-dislocations is a reliable treatment option, yet concerns remain about nonunion and dorsiflexion malunion. The use of a new generation of nitinol staples has proliferated in midfoot arthrodesis. The purpose of this study is to examine the use of nitinol staples in primary arthrodesis of acute Lisfranc fracture-dislocations, comparing outcomes to traditional plate and screw fixation. The primary hypothesis is that nonunion rates are lower with constructs that include nitinol staples than those with plates and screws alone. Secondary hypotheses are: 1. Total operative and tourniquet time are shorter using nitinol staples. 2. Reoperation rates are lower using nitinol staples. 3. Dorsiflexion malunion rates are lower using nitinol staples. 4. Functional outcome scores will indicate comparable post-arthrodesis disability. Methods: Midfoot fracture-dislocations treated with primary arthrodesis by seven foot and ankle orthopaedic surgeons at a tertiary referral center from 1/1/2012 to 8/1/2021 were reviewed. Patients with open fractures, fractures managed with external fixation, Charcot arthropathy, neuropathy, previous midfoot surgery, or concomitant hindfoot/ankle fractures were excluded. Of the 160 eligible patients, 121 met the required 4-month minimum radiographic follow-up. Preoperative imaging and operative records were reviewed, evaluating for associated metatarsal and cuneiform fractures, operative and tourniquet time, joints included, and fixation construct. Patients and individual joints (303 total) were categorized as either staples alone (47 patients), staples plus plates and screws (hybrid) (47), or plates and screws alone (35). Postoperative radiographs at last follow-up were then analyzed for union and malunion at each joint fused. CT scans were used, when available (41 patients), to assess for union. Medical records were reviewed for postoperative complications. FAAM, VR-12, and NPRS were collected. Results: When assessed at the individual joint level, the nonunion rate was higher (8%, 9/101) among joints fixed with plate and screw constructs than with hybrid (2.4%, 1/41) or staple only constructs (1.3%, 2/152) (P = 0.015). Of the 12 nonunions in the study, 6 had either a metatarsal or cuneiform fracture. Median OR and tourniquet time were both shorter for hybrid (92 & 83 minutes) and staple only (67 & 63 minutes) constructs than plate and screw only fixation (107 & 96 minutes) (P = 0.0002 & 0.0009). There were 17 (14%) reoperations including 10 hardware removals, 3 nonunion revisions, and 1 malunion revision. There was no difference in reoperation, malunion (14 total, 12%), or patient reported outcome measure between fixation types. Conclusion: Nitinol staples are effective in achieving bony fusion when used alone or in combination with plates and screws. With lower rates of nonunion and shorter tourniquet and operative time compared to traditional plate and screw fixation, their use should be considered for primary arthrodesis of Lisfranc and midfoot fracture-dislocations. Further studies are needed to determine if staples decrease the risk for dorsiflexion malunion and improve patient reported outcomes.

The engineering challenge of rolling bearing condition monitoring has led to a large number of method developments over the past few years. Most commonly, vibration measurement data are used for fault diagnosis using machine learning algorithms. In current research, purely data-driven deep learning methods are becoming increasingly popular, aiming for accurate predictions of bearing faults without requiring bearing-specific domain knowledge. Opposing this trend in popularity, the present paper takes a more traditional approach, incorporating domain knowledge by evaluating a variety of feature engineering methods in combination with a random forest classifier. For a comprehensive feature engineering study, a total of 42 mathematical feature formulas are combined with the preprocessing methods of envelope analysis, empirical mode decomposition, wavelet transforms, and frequency band separations. While each single processing method and feature formula is known from the literature, the presented paper contributes to the body of knowledge by investigating novel series connections of processing methods and feature formulas. Using the CWRU bearing fault data for performance evaluation, feature calculation based on the processing method of frequency band separation leads to particularly high prediction accuracies, while at the same time being very efficient in terms of low computational effort. Additionally, in comparison with deep learning approaches, the proposed feature engineering method provides excellent accuracies and enables explainability.

Condition monitoring of technical systems has increasing importance for the reduction of downtimes based on unplanned breakdowns. Rolling bearings are a central component of machines because they often support energy-transmitting elements like shafts and spur gears. Bearing damages lead to a high number of machine breakdowns; thus, observing these has the potential to reduce unplanned downtimes. The observation of bearings is challenging since their behavior in operation cannot be investigated directly. A common solution for this task is the measurement of vibration or component temperature, which is able to show an already occurred bearing damage. Measuring the electrical bearing impedance in situ has the ability to gather information about bearing revolution speed and bearing loads. Additionally, measuring the impedance allows for the detection and localization of damages in the bearing, as early research has shown. In this paper, the impedance signal of five fatigue tests is investigated using individual feature selection. Additionally, the feature behavior is analyzed and explained. It is shown that the three different bearing operational time phases can be distinguished via the analysis of impedance signal features. Furthermore, some of the features show a significant change in behavior prior to the occurrence of initial damages before the vibration signals of the test rig vary from a normal state.

Condition monitoring of machine elements becomes more important over the last years. Different approaches to detect failures in mechanical components have been developed. All thesemethods are located at a distance from the point of interest, the observed machine element. This leads to uncertainties in the data, which influences the data quality negatively. Using the electrical impedance for conditionmonitoring enables in situ measurement with reduced uncertainties and higher data quality. In the last years, research considering this topicwas done, but a systematic overview is missing. In this article, a systematic literature research according to the PRISMA approach is fulfilled. The main questions are, what application fields for electrical impedance-based conditionmonitoring approaches exists andwhich research gaps are not addressed yet. At the end, 21 articles are categorized in their application fields. Analyzing their content, research questions are identified which have to be addressed in further investigations. [ABSTRACT FROM AUTHOR]

Within the healthcare system, identification and intervention for intimate partner violence (IPV) are critical, yet often hindered by siloed operations among healthcare workers. Effective interprofessional collaboration is pivotal for timely and appropriate interventions. This article describes an interprofessional educational simulation involving nursing and social work students. Pairs engaged in risk assessment and safety planning for IPV. In the pilot run with 140 nursing and 137 social work students, post-simulation results increased confidence (t = 5.25, p =.001) and positive evaluation of IPV knowledge (t = 63.22, p =.001). Focus groups underscored team synergy, communication skills, and prior experiences as critical elements. Future projects should expand simulation scopes to address diverse situations and include additional professions interacting with survivors. [ABSTRACT FROM AUTHOR]

The opportunities of impedance-based condition monitoring for rolling bearings have been shown earlier by the authors: Changes in the impedance signal and the derived features enable the detection of pitting damages. Localizing and measuring the pitting length in the raceway direction is possible. Furthermore, the changes in features behavior are physically explainable. These investigations were focused on a single bearing type and only one load condition. Different bearing types and load angles were not considered yet. Thus, the impedance signals and their features of different bearing types under different load angles are investigated and compared. The signals are generated in fatigue tests on a rolling bearing test rig with conventional integrated vibration analysis based on structural borne sound. The rolling bearing impedance is gauged using an alternating current measurement bridge. Significant changes in the vibration signals mark the end of the fatigue tests. Therefore, comparing the response time of the impedance can be compared to the vibration signal response time. It can be shown that the rolling bearing impedance is an instrument for condition monitoring, independently from the bearing type. In case of pure radial loads, explicit changes in the impedance signal are detectable, which indicate a pitting damage. Under combined loads, the signal changes are detectable as well, but not as significant as under radial load. Damage-indicating signal changes occur later compared to pure radial loads, but nevertheless enable an early detection. Therefore, the rolling bearing impedance is an instrument for pitting damage detection, independently from bearing type and load angle. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is the most common congenital anomaly, with an overall incidence of approximately 1% in the United Kingdom. Exome sequencing in large CHD cohorts has been performed to provide insights into the genetic aetiology of CHD. This includes a study of 1891 probands by our group in collaboration with others, which identified three novel genes—CDK13, PRKD1, and CHD4, in patients with syndromic CHD. PRKD1 encodes a serine/threonine protein kinase, which is important in a variety of fundamental cellular functions. Individuals with a heterozygous mutation in PRKD1 may have facial dysmorphism, ectodermal dysplasia and may have CHDs such as pulmonary stenosis, atrioventricular septal defects, coarctation of the aorta and bicuspid aortic valve. To obtain a greater appreciation for the role that this essential protein kinase plays in cardiogenesis and CHD, we have analysed a Prkd1 transgenic mouse model (Prkd1em1) carrying deletion of exon 2, causing loss of function. High‐resolution episcopic microscopy affords detailed morphological 3D analysis of the developing heart and provides evidence for an essential role of Prkd1 in both normal cardiac development and CHD. We show that homozygous deletion of Prkd1 is associated with complex forms of CHD such as atrioventricular septal defects, and bicuspid aortic and pulmonary valves, and is lethal. Even in heterozygotes, cardiac differences occur. However, given that 97% of Prkd1 heterozygous mice display normal heart development, it is likely that one normal allele is sufficient, with the defects seen most likely to represent sporadic events. Moreover, mRNA and protein expression levels were investigated by RT‐qPCR and western immunoblotting, respectively. A significant reduction in Prkd1 mRNA levels was seen in homozygotes, but not heterozygotes, compared to WT littermates. While a trend towards lower PRKD1 protein expression was seen in the heterozygotes, the difference was only significant in the homozygotes. There was no compensation by the related Prkd2 and Prkd3 at transcript level, as evidenced by RT‐qPCR. Overall, we demonstrate a vital role of Prkd1 in heart development and the aetiology of CHD. [ABSTRACT FROM AUTHOR]