Psychotic-like experiences in non-clinical subgroups with and without specific beliefs.

BACKGROUND: Assuming a transdiagnostic and extended psychosis phenotype, psychotic-like experiences (PLEs) and psychotic symptoms are on a phenomenological and temporal continuum between clinical and non-clinical populations. Recent research points towards differences in PLE proneness in different subgroups and clinical impact of different PLE subtypes. This study examines the prevalence of PLEs in three groups of individuals with and without specific sets of beliefs aiming to elucidate the question whether proneness to PLEs varies according to traditional versus less traditional supernatural beliefs. METHODS: The anonymized 16-item version of the Prodromal Questionnaire (PQ-16) was used to assess PLEs in three groups including individuals with religious beliefs (RB), belief in esoterism and paranormal phenomena (EB), and those embedded in scientific evidence approach and scepticism towards para-scientific theories (non-believers, NB). Male and female participants between 18 and 90 years were eligible for participation. RESULTS: The sample comprised 159 individuals including 41 RB individuals, 43 EB individuals, and 75 NB individuals. The mean PQ-16 score of the EB individuals (6.86 ± 4.13) was significantly higher compared to NB individuals (3.43 ± 2.99) and to RB individuals (3.38 ± 3.23) with almost twice the score (both p-values < 0.001). There was no significant difference between the PQ-16 scores of the NB group and the RB group (p = 0.935). No significant impact of age (p = 0.330) and gender (p = 0.061) was found on the PQ16-Score. Group affiliation to esoterism was associated with a higher PQ-16 score compared to group affiliation to religious beliefs (p < 0.001) and group affiliation to scepticism (p = 0.011), while the latter two did not differ significantly (p = 0.735). No significant difference was found between the three groups in the degree of distress related to the affirmatively answered PQ-16 items (p = 0.74). CONCLUSION: Under the assumption of a transdiagnostic psychosis phenotype, our findings provide more insight which subgroups within non-clinical samples have a higher likelihood of reporting PLEs.

Limited plasticity of monocyte fate and function associated with epigenetic scripting at the level of progenitors.

Myeloid cell heterogeneity is known, but whether it is cell-intrinsic or environmentally-directed remains unclear. Here, an inducible/reversible system pausing myeloid differentiation allowed the definition of clone-specific functions that clustered monocytes into subsets with distinctive molecular features. These subsets were orthogonal to the classical/nonclassical categorization and had inherent, restricted characteristics that did not shift under homeostasis, after irradiation, or with infectious stress. Rather, their functional fate was constrained by chromatin accessibility established at or before the granulocyte-monocyte or monocyte-dendritic progenitor level. Subsets of primary monocytes had differential ability to control distinct infectious agents in vivo. Therefore, monocytes are a heterogeneous population of functionally restricted subtypes defined by the epigenome of their progenitors that are differentially selected by physiologic challenges with limited plasticity to transition from one subset to another.

Protecting endangered megafauna through AI analysis of drone images in a low-connectivity setting: a case study from Namibia.

Assessing the numbers and distribution of at-risk megafauna such as the black rhino (Diceros bicornis) is key to effective conservation, yet such data are difficult to obtain. Many current monitoring technologies are invasive to the target animals and expensive. Satellite monitoring is emerging as a potential tool for very large animals (e.g., elephant) but detecting smaller species requires higher resolution imaging. Drones can deliver the required resolution and speed of monitoring, but challenges remain in delivering automated monitoring systems where internet connectivity is unreliable or absent. This study describes a model built to run on a drone to identify in situ images of megafauna. Compared with previously reported studies, this automated detection framework has a lower hardware cost and can function with a reduced internet bandwidth requirement for local network communication. It proposes the use of a Jetson Xavier NX, onboard a Parrot Anafi drone, connected to the internet throughout the flight to deliver a lightweight web-based notification system upon detection of the target species. The GPS location with the detected target species images is sent using MQ Telemetry Transport (MQTT), a lightweight messaging protocol using a publisher/subscriber architecture for IoT devices. It provides reliable message delivery when internet connection is sporadic. We used a YOLOv5l6 object detection architecture trained to identify a bounding box for one of five objects of interest in a frame of video. At an intersection over union (IoU) threshold of 0.5, our model achieved an average precision (AP) of 0.81 for black rhino (our primary target) and 0.83 for giraffe (Giraffa giraffa). The model was less successful at identifying the other smaller objects which were not our primary targets: 0.34, 0.25, and 0.42 for ostrich (Struthio camelus australis), springbok (Antidorcas marsupialis) and human respectively. We used several techniques to optimize performance and overcome the inherent challenge of small objects (animals) in the data. Although our primary focus for the development of the model was rhino, we included other species classes to emulate field conditions where many animal species are encountered, and thus reduce the false positive occurrence rate for rhino detections. To constrain model overfitting, we trained the model on a dataset with varied terrain, angle and lighting conditions and used data augmentation techniques (i.e., GANs). We used image tiling and a relatively larger (i.e., higher resolution) image input size to compensate for the difficulty faced in detecting small objects when using YOLO. In this study, we demonstrated the potential of a drone-based AI pipeline model to automate the detection of free-ranging megafauna detection in a remote setting and create alerts to a wildlife manager in a relatively poorly connected field environment.

Long-term effectiveness of Self-Help Plus in refugees and asylum seekers resettled in Western Europe: 12-month outcomes of a randomised controlled trial.

AIMS: As refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH + ), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe. METHODS: Refugees and asylum seekers with psychological distress (General Health Questionnaire-12 ⩾ 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes. RESULTS: Of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389-1.819; p-value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180-1.544; p-value = 0.230). SH + was associated with improvements at 12 months in psychological distress (p-value = 0.004), depressive symptoms (p-value = 0.011) and wellbeing (p-value = 0.001). CONCLUSIONS: The present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence.

Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease.

Abnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and the heart. The bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, but whether cardiovascular disease affects the hematopoietic organ's microvasculature is unknown. Here we show that hypertension, atherosclerosis and myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis and angiogenesis in the bone marrow, altogether leading to overproduction of inflammatory myeloid cells and systemic leukocytosis. Limiting angiogenesis with endothelial deletion of Vegfr2 (encoding vascular endothelial growth factor (VEGF) receptor 2) curbed emergency hematopoiesis after MI. We noted that bone marrow endothelial cells assumed inflammatory transcriptional phenotypes in all examined stages of cardiovascular disease. Endothelial deletion of Il6 or Vcan (encoding versican), genes shown to be highly expressed in mice with atherosclerosis or MI, reduced hematopoiesis and systemic myeloid cell numbers in these conditions. Our findings establish that cardiovascular disease remodels the vascular bone marrow niche, stimulating hematopoiesis and production of inflammatory leukocytes.

Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis.

Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis. Mathematical analysis demonstrates that increased stem cell proliferation expedites somatic evolution and expansion of clones with driver mutations. The experimentally determined division rate elevation in atherosclerosis patients is sufficient to produce a 3.5-fold increased risk of clonal hematopoiesis by age 70. We confirm the accuracy of our theoretical framework in mouse models of atherosclerosis and sleep fragmentation by showing that expansion of competitively transplanted Tet2-/- cells is accelerated under conditions of chronically elevated hematopoietic activity. Hence, increased hematopoietic stem cell proliferation is an important factor contributing to the association between cardiovascular disease and clonal hematopoiesis.

Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells.

A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creERT2; Leprfl/fl mice reveals that leptin's effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes.

Sleep modulates haematopoiesis and protects against atherosclerosis.

Sleep is integral to life1. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease2, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6Chigh monocytes, develop larger atherosclerotic lesions and produce less hypocretin-a stimulatory and wake-promoting neuropeptide-in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin-null and haematopoietic hypocretin-receptor-null mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.

Circuit quantum electrodynamics of granular aluminum resonators.

Granular aluminum (grAl) is a promising high kinetic inductance material for detectors, amplifiers, and qubits. Here we model the grAl structure, consisting of pure aluminum grains separated by thin aluminum oxide barriers, as a network of Josephson junctions, and we calculate the dispersion relation and nonlinearity (self-Kerr and cross-Kerr coefficients). To experimentally study the electrodynamics of grAl thin films, we measure microwave resonators with open-boundary conditions and test the theoretical predictions in two limits. For low frequencies, we use standard microwave reflection measurements in a low-loss environment. The measured low-frequency modes are in agreement with our dispersion relation model, and we observe self-Kerr coefficients within an order of magnitude from our calculation starting from the grAl microstructure. Using a high-frequency setup, we measure the plasma frequency of the film around 70 GHz, in agreement with the analytical prediction.

Health-related quality of life in multiple sclerosis: temperament outweighs EDSS.

BACKGROUND: The influence of personality on health-related quality of life in patients with multiple sclerosis has been the focus of previous studies showing that introversion and neuroticism were related with reduced health related quality of life. However, no data exist on the impact of temperament on quality of life in this patient group. METHODS: Between April 2014 and March 2016 139 multiple sclerosis patients were recruited from a specialized outpatient clinic of the general hospital of Vienna. Health-related quality of life was measured by "The Multiple Sclerosis International Quality of Life Questionnaire (MusiQol)", temperament by "Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Questionnaire - Münster version" (briefTEMPS-M), and disability by the "Expanded disability status scale". All patients underwent a diagnostic psychiatric semi-structured interview (MINI). RESULTS: Known predictors (like disease duration, EDSS, psychiatric co-morbidities, immunomodulatory treatments) explain the proportion of variation in the outcome of MusiQol global index score in 30.9% in multi-variable linear regression analysis. It increased respectively to 40.3, 42.5, and 45.8% if adding the depressive, cyclothymic, or hyperthymic temperament to the list of variables. An increase of depressive and cyclothymic temperament scores significantly reduced global index score of MusiQol (p = 0.005, p = 0.002, respectively), while the hyperthymic temperament significantly raised it (p < 0.001). CONCLUSION: In MS patients, the depressive and cyclothymic temperament predict a lower and hyperthymic temperament an increased health-related quality of life, independent of current disability status, immunomodulatory treatments, and affective co-morbidities.

Fractures of the manubrium sterni: treatment options and a possible classification of different types of fractures.

BACKGROUND: Sternum fractures are mostly located on the sternal corpus, seldom on the manubrium. Fractures of the sternal manubrium are, however, more frequently associated with severe concomitant injuries of thoracic organs, and therefore deserve special attention. In addition, in its function as a capstone in between the anterior chest wall and the shoulder girdle, it is exposed to a multiplicity of forces. Therefore the questions arise what types of fractures are observed in today's clinical practice, how to classify them and which treatment options are available. This study reports on different types of fractures which involve the manubrium sterni. METHODS: Between January 2012 and October 2014, data was collected from all severely injured patients (ISS ≥16), which received a CT scan of the thorax in our Level-I-Trauma Center and retrospectively analyzed concerning sternal fractures. Fracture type, collateral injuries, age, and information about the circumstances of the accident were noted. RESULTS: Of 890 evaluable patients, 154 (17.3%) had a fracture of the sternum and 23 (2.6%) of the manubrium. Fractures of the manubrium appeared in following types: A-type-transverse fracture (n=11) in 1st intercostal space by direct blunt trauma or flexion of the torso with sagittal instability; B-type-oblique fracture (n=9) by seat belt injury with rotatory instability; C-type-combined, more fragmentary fracture (n=3) by direct blunt trauma with simultaneous flexion of the torso and multi directional instability. Fractures only little dislocation were treated conservatively, and unstable fractures were surgically stabilized (n=10). CONCLUSIONS: In summary, three main types of fractures could be found. A-type fractures were stabilized with a longitudinal plate osteosynthesis and B-type fractures with transverse positioned plates. To treat complex C-type fractures, plates with a T- or H-form could be a good solution. Level of evidence: Level III retrospective prognostic cohort study.

Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway.

Macrophages are key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD38 antibody MOR202, currently introduced in multiple myeloma (MM) therapy. Therefore, it is important to understand how antibody-mediated effector functions of myeloma-associated macrophages (MAMs) are regulated. Here, we focused on the effects of vitamin D, a known regulator of macrophage effector functions. Consequently, it was the aim of this study to assess whether modulation of the vitamin D pathway alters the tumoricidal activity of MAMs. Here, we demonstrate that MAMs display a defective vitamin D pathway with reduced expression level of CYP27B1 and limited tumoricidal activity which can be restored by the IMiD lenalidomide in vitro. Furthermore, our data indicate that the vitamin D pathway of MAMs from MM patients does recover during an IMiD-containing therapy shown by an improved MOR202-mediated cytotoxic activity of these MAMs against primary MM cells ex vivo. Here, the ex vivo cytotoxic activity could be further enhanced by vitamin D supplementation. These data suggest that vitamin D holds a key role for the effector functions of MAMs and that vitamin D supplementation in IMiD combination trials could further increase the therapeutic efficacy of anti-CD38 antibodies such as MOR202, which remains to be investigated in clinical studies.

Reduced invasive and muscle-sparing operative approaches to the posterolateral chest wall provide an excellent accessibility for the operative stabilization! : Minimized approaches to the posterolateral chest wall.

PURPOSE: Stabilizing techniques for flail chest injuries are described through wide surgical approaches to the chest wall, especially in the most affected posterior and lateral regions. Severe morbidity due to these invasive approaches needs to be considered due to dissection of the scapular guiding muscles and the risk of injuries to neurovascular bundles. This study discusses possibilities for minimized approaches to the posterior and lateral regions. METHOD: Ten fresh-frozen cadavers in lateral decubitus position were observed on both sides. Each surgical arm was kept mobile during the procedure. Approaches were performed following a standard protocol with muscle-sparing incisions starting with 5 cm in length and extending to 10 and 15 cm. The accessible surface comparing the extensions was measured. Visible ribs were counted. In a next step, MatrixRib® Plates were fixed to those ribs to prove the feasibility of rib stabilization through limited approaches. RESULTS: Combinations of the posterior and lateral minimized approaches allow surgical fixation of 6-9 and 7-11 ribs through 5 and 10 cm incisions, respectively. In the case of an extreme expansion of a rib fracture series, an access extension can be made to 15 cm to be able to adequately supply the entire hemithorax using two approaches. CONCLUSION: Extensive invasive surgical approaches to the thoracic wall can be replaced by reduced invasive and muscle-sparing access combinations. A free-moving positioning of the arm and an accurate preoperative plan for minimizing approaches are essential. Minimally invasive plate techniques are very helpful adjuncts.

Analysis on the Age Distribution of Sternum Fractures.

BACKGROUND: Sternum fractures (SFs) are described as a rare entity of bony fractures. Various accident mechanisms may cause SF such as the direct impact of traffic accidents and also by indirect mechanisms within the framework of falls. Osteoporotic fractures also play an increasing role in SF, but no reliable data on the age distribution of SF in a representative collective have been published so far. MATERIAL AND METHODS: The age distribution of all inpatients treated with SF (S22.2) in Germany from 2005 to 2012 using diagnosis-related group-based routine data was evaluated. Various accident statistics are included in the interpretation of age peaks. RESULTS: A total of 47,893 patients (24,960 as main diagnosis and 22,933 as secondary diagnosis) were included in the study. SF is a rarity in childhood, with a share of 1.83% before the age of 16 years, followed by a sudden increase in the frequency up to the age of 20 years. A decrease in the frequency is observed up to the age of 35 years before it increases again to the age of 75 years. Three age peaks can be observed at 18, 55, and 75 years. Those who are older than 65 years account for 43.3% of total SF. DISCUSSION AND CONCLUSION: The first age summit after the age of 16 years shows an identical course to the frequency of traffic accidents of this age group, as well as the decline to the fourth decade and the subsequent resurgence up to the fifth decade. After 65 years, the incidence of accidents increases, in particular, the risk of falling in elderly people. In the context of a weaker bone structure, low falls are a common course for fragility fractures. The present analysis of routines shows for the first time the age distribution of the SF taking into account all hospital cases of the observation period.

The Operative Management of Flail Chest Injuries with Concomitant Sternal Fracture.

Background: Flail Chest Injuries (FCI) are one of the most severe thoracic injuries. Moreover, an additional sternal fracture (SF) even worsens the outcome, such as the duration of mechanical ventilation, therefore an surgical fixation of the fractures could be considered in certain cases to improve the weaning from the ventilator. This paper aims to emphasize on the management of different types of SF in FCI. Methods: All surgically treated cases (2012-2016) that showed the combination of FCI and SF have been evaluated for their clinical details, the morphology of the fractures and the technical aspects of the surgical procedure in a retrospective investigation. Results: All of the SF (n=15) had been fixed by locked plate osteosynthesis through a median approach in a supine position. Three main regions of the sternum showed the need for different fixation strategies: the upper manubrium, central and lower corpus sterni. Concomitant rib fractures were addressed either through the same approach or through additional limited incisions. Conclusions: Combinations of SF and FCI are high risc injuries with high demand on surgical skills. They can be properly fixed with a locking plate osteosynthesis through a combination of limited incisions employing different types of plates depending on the type of SF.

Surgical Stabilization of Costoclavicular Injuries - A Combination of Flail Chest Injuries and a Clavicula Fracture.

Background: Flail chest injuries (FCI) are associated with a high morbidity and mortality rate. As a concomitant clavicle fracture in FCI even worsens the outcome, the question is how can those costoclavicular injuries (CCI) be managed surgically. Methods: 11 patients with CCI were surgically treated by a locked plate osteosynthesis of the Clavicle and the underlying ribs through limited surgical approaches under general anesthesia. Patients were followed up after 2, 6, 12, 26 and 52 weeks. Results: All patients showed severe chest wall deformity due to severely displaced fractures of the ribs and the clavicle. They were suffering from pain and restriction of respiratory movements. The chest wall could be restored to normal shape in all cases with uneventful bone healing and a high patient convenience. Fractures of the clavicle and the second rib were managed through an innovative clavipectoral approach, the others through standard approaches to the anterolateral and the posterolateral chest wall. Two patients complained about numbness around the lateral approach and lasting periscapular pain. Conclusions: Surgical stabilization might be the appropriate therapy in CCI with dislocated fractures since they would cause severe deformity and loss of function of the chest wall and the shoulder.

Comparative studies of different types of osteosynthesis on the human corpse preparation in bilateral antero-lateral flail chest.

INTRODUCTION: Bilateral flail chest injuries are challenging in treatment and comparatively often require an operative stabilization of the anterior chest wall to re-establish normal physiological conditions of the chest wall in shape and statics. Various procedures have been described which are technically sophisticated for the surgeon. Consequently there is an increasing interest in potentials of operative care and their effectiveness on the anterolateral chest wall. MATERIALS AND METHODS: 12 Human cadavers were prepared and the natural Sternum Position (NP) was marked. A digital probe was fixed to the sternum at the height of the 4th intercostal space in order to measure and compare the stability of the thorax. Readings were taken of the sternal displacement at 1-5cm sagittal distance from NP in starting conditions and from every combination of materials. Serial osteotomies were performed on 2 locations on ribs 2-8 to induce bilateral flail chest. Afterwards the stabilization was achieved with different implants: RESULTS: The osteotomies lead to a subsidence of the sternum occurred to almost 75 mm from NP which corresponds to a maximal unstable situation. The unstable chest wall showed substantially more stabilization through the use of locking plates. Our materialcombinations showed a stability of up to 60% of normal. The more ribs were treated osteosynthetically, the higher the stability of the chest wall. DISCUSSION AND CONCLUSIONS: Locking plate fixation offers anatomically realignment of the ribs whereas metal strut support only lifts up the chest wall, but could not provide realignment of the dislocated ribs.