Exploring individual's public trust in the NHS Test and Trace System - A pragmatic reflexive thematic analysis.

Context: Digital contact tracing uses automated systems and location technology embedded on smartphone software for efficient identification of individuals exposed to COVID-19. Such systems are only effective with high compliance, yet compliance is mediated by public trust in the system. This work explored the perception of individual's trust and expectation of the broader Test and Trace system in the United Kingdom (UK) with the upcoming release of the National Health Service's (NHS) COVID-19 app as a case example. Methods: Twelve adults underwent online semi-structured interviews in August 2020, prior to public availability of the COVID-19 app. Pragmatic reflexive thematic analysis was applied inductively to explore common themes between participants, using an organic and recursive process (Braun & Clarke, 2019). Results: Themes highlighted features of the technology that would be perceived to be trustworthy (Theme 1), and concerns relating to i) whether users would comply with a T&T system (Theme 2) and ii) how a T&T system would handle user's personal data (Theme 3). Two further themes built on aspects of automation within a T&T system and its impact on trust (Theme 4) and how the media altered perceptions of the T&T system (Theme 5). Conclusions: Participants outlined the need for different user requirements that could be built into the NHS COVID-19 app that would support increased adherence. Concurrently, participants raised questions surrounding personal data and privacy of their data, plus the level of automated versus manual tasks, which impacted perception of trust in the app and wider system. Additionally, themes highlighted that T&T systems do not happen within a vacuum, but within a pre-existing environment influenced by variables such as the media and perception of other's compliance to T&T. Implications: Since it's roll-out, controversies surrounding the UK T&T system include concerns about privacy, stigma and uptake. Considering the current piece of work, which anticipated similar concerns prior to public access to COVID-19 app, engaging with the public may have been an important step in improving the perception and compliance with the app. Principles fundamental to patient and public involvement (PPI) and Responsible Research and Innovation (RRI) such as the inclusion of the public in the early development of research and aligning the outcomes of research and innovation with broader societal values and expectations would have been well-applied to this system and should be applied to future autonomous systems requiring high public uptake.

Personal, financial and time burden in inherited ichthyoses: A survey of 144 patients in a university-based setting.

BACKGROUND: Patients with inherited ichthyosis suffer from scaling due to mutations affecting the epidermal barrier. Symptomatic treatment with ointments, bathing and mechanical scale removal can alleviate the disease, but therapy is time and cost intensive. OBJECTIVES: We investigated costs, time and disease burden of ichthyoses. The study addresses difficulties of the healthcare situation for patients with ichthyoses and reveals potential improvements. MATERIALS AND METHODS: We developed a questionnaire addressing time and financial effort for the treatment. Additionally, we collected data of the Dermatology Life Quality Index (DLQI) and the Pruritus Life Quality (5PLQ) questionnaires to determine the impact of ichthyosis and associated pruritus on quality of life (QoL). RESULTS: We recruited 144 patients with ichthyosis (median age: 23; 53.5% female) from the Department of Dermatology in Muenster (Germany) and the German patient support group including common, rare and syndromic subtypes. Eighty-seven percent reported applying topical therapeutics at least once per day, 66.4% several times with an overall median duration of 15 min. Highest single expenditure of time was due to balneotherapy (n = 115; median bathing time: 40 min). In 81.9%, the health insurance did not completely cover the costs for topical treatment causing additional financial burden to the patient with a median of 71 € per quarter, herein creams being the largest cost factor (50 €). Patients with Netherton syndrome showed the highest median expenditure (170 €). The QoL impairment under treatment was moderate (median DLQI: 8.5 points). Pruritus was prevalent in 79.9% and showed a distinct impact on QoL (median 5PLQ: 7.5 points) without any significant difference between the subtypes (p = 0.37). CONCLUSION: Patients suffering from ichthyoses have a large and lifelong overall burden in mild and severe subtypes. Since continuous topical treatment is required, financial and psychosocial support needs to be considered beyond dermatological care.

French national protocol for the management of congenital ichthyosis.

Congenital ichthyoses (CI) comprise a heterogeneous group of monogenic genetic skin diseases characterized by diffuse scaling, often associated with skin inflammation. Diagnosis of the individual form of ichthyosis is complex and is guided by clinical expertise. CI usually has a major impact on quality of life (QOL) and thus requires lifelong treatment. To date, there are no curative therapies, although various symptomatic treatment options exist. The present protocol for the management of CI has been drawn up in accordance with the recommendations published in 2012 by the French National Authority for Health, based on a literature review, with the help and validation of members of the French network for rare skin diseases (FIMARAD). It provides a summary of evidence and expert-based recommendations and is intended to help clinicians with the management of these rare and often complex diseases.

Recruiting refugees and migrants as potential hematopoietic stem cell donors to serve patients of comparable ethnicities with rare human leucocyte antigen patterns - The BluStar.NRW project in North Western Germany.

Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.

The enigma of incisional hernia prediction unraveled: external validation of a prognostic model in colorectal cancer patients.

PURPOSE: Accurate prediction of hernia occurrence is vital for surgical decision-making and patient management, particularly in colorectal surgery patients. While a hernia prediction model has been developed, its performance in external populations remain to be investigated. This study aims to validate the existing model on an external dataset of patients who underwent colorectal surgery. METHODS: The "Penn Hernia Calculator" model was externally validated using the Hughes Abdominal Repair Trial (HART) data, a randomized trial comparing colorectal cancer surgery closure techniques. The data encompassed demographics, comorbidities, and surgical specifics. Patients without complete follow-up were omitted. Model performance was assessed using key metrics, including area under the curve (AUC-ROC and AUC-PR) and Brier score. Reporting followed the TRIPOD consensus. RESULTS: An external international dataset consisting of 802 colorectal surgery patients were identified, of which 674 patients with up to 2 years follow-up were included. Average patient age was 68 years, with 63.8% male. The average BMI was 28.1. Prevalence of diabetes, hypertension, and smoking were 15.7%, 16.3%, and 36.5%, respectively. Additionally, 7.9% of patients had a previous hernia. The most common operation types were low anterior resection (35.3%) and right hemicolectomy (34.4%). Hernia were observed in 24% of cases by 2-year follow-up. The external validation model revealed an AUC-ROC of 0.66, AUC-PR of 0.72, and a Brier score of 0.2. CONCLUSION: The hernia prediction model demonstrated moderate performance in the external validation. Its potential generalizability, specifically in those undergoing colorectal surgery, may suggest utility in identifying and managing high-risk hernia candidates.

Optimal computed tomography-based biomarkers for prediction of incisional hernia formation.

PURPOSE: Unstructured data are an untapped source for surgical prediction. Modern image analysis and machine learning (ML) can harness unstructured data in medical imaging. Incisional hernia (IH) is a pervasive surgical disease, well-suited for prediction using image analysis. Our objective was to identify optimal biomarkers (OBMs) from preoperative abdominopelvic computed tomography (CT) imaging which are most predictive of IH development. METHODS: Two hundred and twelve rigorously matched colorectal surgery patients at our institution were included. Preoperative abdominopelvic CT scans were segmented to derive linear, volumetric, intensity-based, and textural features. These features were analyzed to find a small subset of OBMs, which are maximally predictive of IH. Three ML classifiers (Ensemble Boosting, Random Forest, SVM) trained on these OBMs were used for prediction of IH. RESULTS: Altogether, 279 features were extracted from each CT scan. The most predictive OBMs found were: (1) abdominopelvic visceral adipose tissue (VAT) volume, normalized for height; (2) abdominopelvic skeletal muscle tissue volume, normalized for height; and (3) pelvic VAT volume to pelvic outer aspect of body wall skeletal musculature (OAM) volume ratio. Among ML prediction models, Ensemble Boosting produced the best performance with an AUC of 0.85, accuracy of 0.83, sensitivity of 0.86, and specificity of 0.81. CONCLUSION: These OBMs suggest increased intra-abdominopelvic volume/pressure as the salient pathophysiologic driver and likely mechanism for IH formation. ML models using these OBMs are highly predictive for IH development. The next generation of surgical prediction will maximize the utility of unstructured data using advanced image analysis and ML.

The underwater soundscape of the North Sea.

As awareness on the impact of anthropogenic underwater noise on marine life grows, underwater noise measurement programs are needed to determine the current status of marine areas and monitor long-term trends. The Joint Monitoring Programme for Ambient Noise in the North Sea (JOMOPANS) collaborative project was funded by the EU Interreg to collect a unique dataset of underwater noise levels at 19 sites across the North Sea, spanning many different countries and covering the period from 2019 to 2020. The ambient noise from this dataset has been characterised and compared - setting a benchmark for future measurements in the North Sea area. By identifying clusters with similar sound characteristics in three broadband frequency bands (25-160 Hz, 0.2-1.6 kHz, and 2-10 kHz), geographical areas that are similarly affected by sound have been identified. The measured underwater sound levels show a persistent and spatially uniform correlation with wind speed at high frequencies (above 1 kHz) and a correlation with the distance from ships at mid and high frequencies (between 40 Hz and 4 kHz). Correlation with ocean current velocity at low frequencies (up to 200 Hz), which are susceptible to nonacoustic contamination by flow noise, was also evaluated. These correlations were evaluated and simplified linear scaling laws for wind and current speeds were derived. The presented dataset provides a baseline for underwater noise measurements in the North Sea and shows that spatial variability of the dominant sound sources must be considered to predict the impact of noise reduction measures.

Simultaneous direct measurement of the electrocaloric and dielectric dynamics of ferroelectrics with microsecond temporal resolution.

A contactless technique for direct time-resolved measurements of the full dynamics of the adiabatic temperature change in electrocaloric materials is introduced. The infrared radiation emitted by the electrocaloric sample is sensitively detected with µs time resolution and mK temperature resolution. We present time-resolved measurements of the electrocaloric effect up to kHz frequencies of the driving electric field and down to small field strengths. The simultaneous recording of transients for applied electric field and induced polarization gives a comprehensive view of the correlation of electrocaloric and ferroelectric properties. The technique can further be applied to the continuous measurement of fatigue for >106 electric field cycles.

Transversus abdominis release with biosynthetic mesh for large ventral hernia repair: a 5-year analysis of clinical outcomes and quality of life.

INTRODUCTION: Transversus abdominis release (TAR) may provide an optimal plane for mesh placement for large ventral hernias requiring medial myofascial flap advancement. Long-term outcomes of TAR for large ventral hernia repair (VHR) remains under-studied. This study aims to assess longitudinal clinical outcomes and quality of life (QoL) following large VHR with TAR and resorbable biosynthetic mesh. METHODS: Retrospective review of clinical outcomes and prospective QoL was performed for patients undergoing VHR with poly-4-hydroxybutyrate mesh and TAR from 2016 to 2021. Patients with ≤ 24 months of follow-up, defects ≤ 150 cm2, and parastomal hernias were excluded. Cost-related data was collected for each patient's hospital course. QoL was compared using paired Wilcoxon signed-rank tests. RESULTS: Twenty-nine patients met inclusion criteria. Median age and BMI were 61 years (53.2-68.1 years) and 31.4 kg/m2 (26.1-35.3 kg/m2). Average hernia defect was 390cm2 ± 152.9 cm2. All patients underwent previous abdominal surgery and were primarily Ventral Hernia Working Group 2 (58.6%). Two hernia recurrences (6.9%) occurred over the median follow-up period of 63.1 months (IQR 43.7-71.3 months), with no cases of mesh infection or explantation. Delayed healing and seroma occurred in 27 and 10.3% of patients, respectively. QoL analysis identified a significant improvement in postoperative QoL (p < 0.005), that continued throughout the 5-year follow-up period, with a 41% overall improvement. Cost analysis identified the hospital revenue generated was approximately equal to the direct costs of patient care. Higher costs were associated with ASA class and length of stay (p < 0.05). CONCLUSION: Large VHR with resorbable biosynthetic mesh and TAR can be performed safely, with a low recurrence and complication rate, acceptable hospital costs, and significant improvement in disease-specific QoL at long-term follow-up.

Are you better than me? Social comparisons in carrion crows (Corvus corone).

Comparing oneself to others is a key process in humans that allows individuals to gauge their performances and abilities and thus develop and calibrate their self-image. Little is known about its evolutionary foundations. A key feature of social comparison is the sensitivity to other individuals' performance. Recent studies on primates produced equivocal results, leading us to distinguish between a 'strong' variant of the social comparison hypothesis formulated for humans and a 'weak' variant found in non-human primates that would comprise some elements of human social comparison. Here, we focus on corvids that are distantly related to primates and renowned for their socio-cognitive skills. We were interested in whether crows' task performances were influenced (i) by the presence of a conspecific co-actor performing the same discrimination task and (ii) by the simulated acoustic cues of a putative co-actor performing better or worse than themselves. Crows reached a learning criterion quicker when tested simultaneously as compared to when tested alone, indicating a facilitating effect of social context. The performance of a putative co-actor influenced their performance: crows were better at discriminating familiar images when their co-actor was better than they were. Standard extremity (how pronounced the difference was between the performance of the subject and that of the co-actor), and category membership (affiliation status and sex), of the putative co-actors had no effect on their performance. Our findings are in line with the 'weak' variant of social comparison and indicate that elements of human social comparison can be found outside of primates.

Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion.

BACKGROUND: Type 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and associated with poor outcome after myocardial infarction (MI). In T2DM, cardiac metabolic flexibility, i.e. the switch between carbohydrates and lipids as energy source, is disturbed. The RabGTPase-activating protein TBC1D4 represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle by controlling glucose transporter GLUT4 translocation. A human loss-of-function mutation in TBC1D4 is associated with impaired glycemic control and elevated T2DM risk. The study's aim was to investigate TBC1D4 function in cardiac substrate metabolism and adaptation to MI. METHODS: Cardiac glucose metabolism of male Tbc1d4-deficient (D4KO) and wild type (WT) mice was characterized using in vivo [18F]-FDG PET imaging after glucose injection and ex vivo basal/insulin-stimulated [3H]-2-deoxyglucose uptake in left ventricular (LV) papillary muscle. Mice were subjected to cardiac ischemia/reperfusion (I/R). Heart structure and function were analyzed until 3 weeks post-MI using echocardiography, morphometric and ultrastructural analysis of heart sections, complemented by whole heart transcriptome and protein measurements. RESULTS: Tbc1d4-knockout abolished insulin-stimulated glucose uptake in ex vivo LV papillary muscle and in vivo cardiac glucose uptake after glucose injection, accompanied by a marked reduction of GLUT4. Basal cardiac glucose uptake and GLUT1 abundance were not changed compared to WT controls. D4KO mice showed mild impairments in glycemia but normal cardiac function. However, after I/R D4KO mice showed progressively increased LV endsystolic volume and substantially increased infarction area compared to WT controls. Cardiac transcriptome analysis revealed upregulation of the unfolded protein response via ATF4/eIF2α in D4KO mice at baseline. Transmission electron microscopy revealed largely increased extracellular matrix (ECM) area, in line with decreased cardiac expression of matrix metalloproteinases of D4KO mice. CONCLUSIONS: TBC1D4 is essential for insulin-stimulated cardiac glucose uptake and metabolic flexibility. Tbc1d4-deficiency results in elevated cardiac endoplasmic reticulum (ER)-stress response, increased deposition of ECM and aggravated cardiac damage following MI. Hence, impaired TBC1D4 signaling contributes to poor outcome after MI.

Platelets modulate cardiac remodeling via the collagen receptor GPVI after acute myocardial infarction.

Introduction: Platelets play an important role in cardiovascular diseases. After acute myocardial infarction, platelets display enhanced activation and migrate into the infarct zone. Furthermore, platelets trigger acute inflammation and cardiac remodeling leading to alterations in scar formation and cardiac function as observed in thrombocytopenic mice. GPVI is the major collagen receptor in platelets and important for platelet activation and thrombus formation and stability. Antibody induced deletion of GPVI at the platelet surface or treatment of mice with recombinant GPVI-Fc results in reduced inflammation and decreased infarct size in a mouse model of AMI. However, the role of GPVI has not been fully clarified to date. Methods/Results: In this study, we found that GPVI is not involved in the inflammatory response in experimental AMI using GPVI deficient mice that were analyzed in a closed-chest model. However, reduced platelet activation in response to GPVI and PAR4 receptor stimulation resulted in reduced pro-coagulant activity leading to improved cardiac remodeling. In detail, GPVI deficiency in mice led to reduced TGF-ß plasma levels and decreased expression of genes involved in cardiac remodeling such as Col1a1, Col3a1, periostin and Cthrc1 7 days post AMI. Consequently, collagen quality of the scar shifted to more tight and less fine collagen leading to improved scar formation and cardiac function in GPVI deficient mice at 21d post AMI. Conclusion: Taken together, this study identifies GPVI as a major regulator of platelet-induced cardiac remodeling and supports the potential relevance of GPVI as therapeutic target to reduce ischemia reperfusion injury and to improve cardiac healing.

[Eosinophilic dermatoses]. / Eosinophile Dermatosen.

Eosinophilic dermatoses are a heterogeneous group of rare diseases that histopathologically display the defining pattern of an eosinophil-rich dermal infiltrate. In these eosinophilic dermatoses, a histopathologic pattern called flame figures, which result from degranulation of eosinophils in the tissue, can be observed. Although eosinophil granulocytes can also be detected in other dermatoses such as atopic dermatitis, urticaria, prurigo and bullous pemphigoid, the eosinophil-rich infiltrate is decisive for classic eosinophilic dermatoses. Accordingly, eosinophilic dermatoses include hypereosinophilic syndrome, eosinophilic fasciitis, granuloma faciale, pustular sterile eosinophilia, and angiolymphoid hyperplasia with eosinophilia. These eosinophilic dermatoses display clinical different patterns and are discussed in this article, as well as the interesting eosinophils and novel therapeutic options.

The acoustic environment before and during the SARS-CoV-2 lockdown in a major German city as measured by ecoacoustic indices.

The SARS-CoV-2 pandemic drastically changed daily life. Lockdown measures resulted in reduced traffic mobility and, subsequently, a changed acoustic environment. The exceptional lockdown was used to analyze its impact on the urban acoustic environment using ecoacoustic indices. Using data from 22 automated sound recording devices located in 9 land use categories (LUCs) in Bochum, Germany, the normalized difference soundscape index (NDSI) and Bioacoustics index (BIO) were explored. The NDSI quantifies the proportion of anthropophonic to biophonic sounds, and BIO quantifies the total sound activities of biological sources. The mean differences and standard deviation (SD) were calculated 5 weeks before and 5 weeks during the first lockdown. Pronounced peaks for the NDSI and BIO before lockdown that diminished markedly during lockdown were observed, however, with distinct differences in terms of the LUC. The mean NDSI increased from 0.00 (SD = 0.43) to 0.15 (SD = 0.50), the mean BIO decreased from 4.74 (SD = 2.64) to 4.03 (SD = 2.66). Using the NDSI and BIO together reveals that changes of the acoustic environment during lockdown are mainly driven by decreased anthropophonic sound sources. These results suggest that further studies are needed to tailor ecoacoustic indices more accurately to conditions of the urban environment.

National epidemiologic trends (2008-2018) in the United States for the incidence and expenditures associated with incisional hernia in relation to abdominal surgery.

PURPOSE: It is unknown whether the trend of rising incisional hernia (IH) repair (IHR) incidence and costs until 2011 currently persists. We aimed to evaluate how the IHR procedure incidence, cost and patient risk-profile have changed over the last decade relative to all abdominal surgeries (AS). METHODS: Repeated cross-sectional analysis of 38,512,737 patients undergoing inpatient 4AS including IHR within the 2008-2018 National Inpatient Sample. Yearly incidence (procedures/1,000,000 people [PMP]), hospital costs, surgical and patient characteristics were compared between IHR and AS using generalized linear and multinomial regression. RESULTS: Between 2008-2018, 3.1% of AS were IHR (1,200,568/38,512,737). There was a steeper decrease in the incidence of AS (356.5 PMP/year) compared to IHR procedures (12.0 PMP/year) which resulted in the IHR burden relative to AS (2008-2018: 12,576.3 to 9,113.4 PMP; trend difference P < 0.01). National costs averaged $47.9 and 1.7 billion/year for AS and IHR, respectively. From 2008-2018, procedure costs increased significantly for AS (68.2%) and IHR (74.6%; trends P < 0.01). Open IHR downtrended (42.2%), whereas laparoscopic (511.1%) and robotic (19,301%) uptrended significantly (trends P < 0.01). For both AS and IHR, the proportion of older (65-85y), Black and Hispanic, publicly-insured, and low-income patients, with higher comorbidity burden, undergoing elective procedures at small- and medium-sized hospitals uptrended significantly (all P < 0.01). CONCLUSION: IH persists as a healthcare burden as demonstrated by the increased proportion of IHR relative to all AS, disproportionate presence of high-risk patients that undergo these procedures, and increased costs. Targeted efforts for IH prevention have the potential of decreasing $17 M/year in costs for every 1% reduction.

Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Single-particle and collective excitations of polar water molecules confined in nano-pores within a cordierite crystal lattice.

Recently, the low-temperature phase of water molecules confined within nanocages formed by the crystalline lattice of water-containing cordierite crystals has been reported to comprise domains with ferroelectrically ordered dipoles within the a, b-planes which are antiferroelectrically alternating along the c-axis. In the present work, comprehensive broad-band dielectric spectroscopy is combined with specific heat studies and molecular dynamics and Monte Carlo simulations in order to investigate in more detail the collective modes and single-particle excitations of nanoconfined water molecules. From DFT-MD simulations we reconstruct the potential-energy landscape experienced by the H2O molecules. A rich set of anisotropic temperature-dependent excitations is observed in the terahertz frequency range. Their origin is associated with the complex rotational/translational vibrations of confined H2O molecules. A strongly temperature dependent relaxational excitation, observed at radio-microwave frequencies for the electric field parallel to the crystallographic a-axis, E||a is analyzed in detail. The temperature dependences of loss-peak frequency and dielectric strength of the excitation together with specific heat data confirm a ferroelectric order-disorder phase transition at T0 ≈ 3 K in the network of H2O dipoles. Additional dielectric data are also provided for polarization E||b, too. Overall, these combined experimental investigations enable detailed conclusions concerning the dynamics of the confined water molecules that develop within their microscopic energy landscapes.

[Internal medical emergencies in the pregnant patient : Peripartum sepsis, metabolic derailment, endocrinological emergencies and pulmonary edema]. / Internistische Notfälle bei der schwangeren Patientin : Peripartale Sepsis, Stoffwechselentgleisungen, endokrinologische Notfälle und Lungenödem.

Peripartum emergencies that require intensive medical care represent a major challenge for the interdisciplinary treatment team. Due to physiological changes in pregnant women symptoms can be masked and the initiation of treatment is delayed. Peripartum sepsis has a relatively high incidence. The anti-infective treatment depends on the spectrum of pathogens to be expected. Endocrinological emergencies are rare but can be fulminant and fatal. The development of ketoacidosis is favored by decreased bicarbonate buffer and placental hormones. In the case of thyrotoxicosis, propylthiouracil and thiamazole are available for treatment depending on the stage of gestation. Sheehan's syndrome is an infarction of the anterior lobe of the pituitary gland during a hemorrhage. Due to the loss of production of vital hormones, this can be fatal. The development of pulmonary edema is just as acute. This is favored by physiological changes during pregnancy. The differentiation between hypertensive and hypotensive pulmonary edema is important for the causal treatment.