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It was reported that mRNA-based Covid-19 vaccines rarely cause myocarditis. Although endomyocardial biopsy (EMB) is considered the gold standard for diagnosing myocarditis, no standardized study has been performed after Covid-19 vaccination in humans. Because routine EMB is frequently performed in heart transplant recipients (HTX), we aimed here to investigate effects of Covid-19 vaccination by analyzing myocardial inflammation with state-of-the-art quantitative immunohistochemistry. Consecutive patients after HTX who underwent routine EMB at a median of 167 days before and 136 days after the first Covid 19 vaccination with an mRNA vaccine were included and divided into groups with and without postvaccination inflammatory response, defined as increased CD3+ lymphocyte count >14/ mm2. Patients with evidence of rejection (ISHLT grade >1) or >14 CD3+ lymphocytes/mm2 at baseline were excluded. The final analysis included 46 patients with a mean age of 63 years and a time after HTX of 2.4 years. Thirty-six (78%) patients remained below the threshold of 14 CD3+ lymphocytes/mm2. However, in 10 (22%) recipients, we detected significant leukocyte infiltration by quantitative analysis of EMB after vaccination (4 vs. 33.7 leukocytes/ mm2, p=0.001). The groups did not differ with respect to age (63 vs. 57 years, p=0.21), body mass index (25 vs. 24 kg/m2, p=0.24), NYHA class (≥2 at 19 vs. 10%, p=0.4), NT-ProBNP levels (592 vs. 514 ng/l, p=0.55) or myocardial CD3+ cell count (4.9 vs. 2.6 cells/mm2, p=0.07) before vaccination. Patients with leukocyte infiltration remained clinically inapparent with stable NYHA class (≥2 in 10 vs. 20%, p=0.99) and did not have increased NT-ProBNP levels (514 vs. 478 ng/l, p=0.03). No hospitalizations for suspected myocarditis were reported. For the first time, we report subclinical myocardial leukocyte infiltration after Covid-19 mRNA vaccination in one in five patients without clinical sequelae during the short observation period. [ABSTRACT FROM AUTHOR]

Abstract: During the last decades the Aral Sea basin has suffered an enormous depletion of water resources within its lakes and rivers with consequences for society, economy, and nature. Within this model study, Global Change impacts on the Amu Darya and Syr Darya rivers, as well as on the Aral Sea itself, are being analysed for the period 1958–2002. In a first step, a multi-annual data base on crop specific irrigated areas has been set-up, which has then been integrated in the hydrology and water use model WaterGAP3. As a second step, anthropogenic water abstractions have been calculated, which were then assimilated in the simulation of river runoff of the Amu Darya and Syr Darya. The last step includes the simulation of the water balance of the Aral Sea, by taking into account modelled river inflow. Within WaterGAP3, the water use module has been switched on and off to separate the impacts of Climate and Global Change (i.e. water abstractions). Irrigation water abstractions are very well represented by WaterGAP3 and lie within the range of reported values. Modelled river discharge also shows a good fit to observed data, whereas phases are in sync but volumes are slightly overestimated. Simulated volumes of the Aral Sea itself are well reflected by the model, though results for the period 1990–2002 are too high. In this study, the Climate Change impacts are much smaller (14%) than the water use impacts (86%) on the shrinkage of the Aral Sea. Finally, an outlook on potential scenario model studies is given, which could analyse the different strategies of mitigation and adaptation of Global Change in the Aral Sea basin. [Copyright &y& Elsevier]

Objectives Functional re-entry is thought to represent the predominant mechanism underlying ventricular arrhythmias. Functional conduction block may be caused by regional dispersion of refractoriness (ERP). Dispersion of ERP may not be evident at baseline, but may occur with sudden changes in heart rate, as ventricular arrhythmias are commonly induced by short-long-short cycles. Methods We examined the dynamics of local ERPs at two left ventricular (LV) sites in dogs with either no structural heart disease or biventricular hypertrophy (BVH). ERPs were determined at each of four bipoles of two adjacent needle electrodes in the LV apex and the lateral wall. The stimulation protocol included two different basic cycle lengths, one or two longer cycles after a train of 6 or 5 shorter cycles, and one shorter cycle after a train of 6 longer cycles. Results In normal dogs, a significant apicolateral ERP gradient was only evident with the longer basic cycle length. One shorter cycle was sufficient to dissolve that gradient. One longer cycle was enough to create a regional ERP gradient. Dynamic regional gradients occurred because the apex responded more markedly and more readily to abrupt changes in cycle length. BVH led to an increase in ERP at both LV sites and to an aggravation of regional ERP gradients. Conclusions Dynamic ERP behavior seems to depend on topography and underlying pathology. Abrupt changes in heart rate might induce dynamic refractory gradients between various regions of the normal heart, but also between adjacent regions inhomogenously affected by hypertrophy. [ABSTRACT FROM AUTHOR]

This article discusses the incidence and risk factors for malignancies in patients who have undergone heart transplantation at a single center. The study analyzed data from 296 patients who had undergone heart transplantation between September 2010 and August 2023. The overall incidence of malignancy was 8.8%, with skin cancer being the most common type. The study found that the switch to everolimus as part of the immunosuppression therapy did not reduce the incidence of malignancies. Early detection through close follow-up is important for improving the prognosis of these malignancies. [Extracted from the article]

This article discusses the use of temporary mechanical circulatory support (TMCS) as a bridge-to-transplant strategy for patients with cardiogenic shock who require a heart transplant. The study included 296 patients who underwent heart transplant, with 14 of them being on TMCS at the time of transplantation. The TMCS patients had higher rates of postoperative circulatory failure and mortality compared to patients without TMCS. The study highlights the complexity and critical preoperative state of TMCS patients and suggests that while heart transplantation is possible for these patients, their outcomes may be impaired. [Extracted from the article]

Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause development of cardiac allograft vasculopathy (CAV). Consequently, frequent monitoring and prophylaxes for CMV-DNAemia within the first weeks after HTx is regularly performed. However, CMV-DNAemia after termination of the perioperative prophylaxes is commonly observed. All adult patients undergoing HTx between September of 2010 and 2021 surviving the first 90 days (n=196) were retrospectively reviewed in September 2022. Patients were divided regarding the prevalence of CMV-DNAemia during the first postoperative year after termination of the institutional 90-day CMV prophylaxis. A total of n=35 (20.1%) developed CMV-DNAemia (CMV group) and were compared to patients without CMV-DNAemia (Controls, n=139). The remaining patients (n=22) were excluded due to incomplete data. CMV prophylaxis consisted of val-/ganciclovir as well as intravenous CMV immunoglobulin for high-risk D+/R- CMV IgG match. D+/R- and D-/R+ serology was significantly increased and D-/R- decreased in the CMV group (p<.01). In addition, mean age was 57.7±8.7 years but only 53.6±10.0 years for Controls (p=.03). Furthermore, ICU (p=.02) and total hospital stay (p=.03) after HTx was about 50% longer compared to the controls. Interestingly, incidence of CMV-DNAemia during the regular prophylaxis was only numerically increased in the CMV group (5.7% respectively.7%, p=.10), the same effect was also overserved for postoperative infective complications. Multivariate analyses could confirm that increased recipient age and D+/R- and D-/R+ CMV IgG match of donors and recipients were independent risk factors for post-prophylaxis CMV-DNAemia within the first year after heart transplantation. Our data should raise awareness for CMV-DNAemia after termination of regular prophylaxis schemes, as this affects one of five HTx patients and can contribute to the development of CAV. Especially old recipients as well as D+/R- and D-/R+ serology share an elevated risk for late CMV-DNAemia. For these patients, prolongation or repetition of CMV prophylaxis including antiviral drugs and CMV immunoglobulins may be considered. [ABSTRACT FROM AUTHOR]

The pressure and temperature dependence of the photoisomerization rate coefficient of trans-stilbene in the S1 state have been measured in the solvents C2H6, C3H8, C4H10, Xe, Co2, SF6, and CHF3. At constant temperature, the pressure dependences up to 6 kbar can be well represented by the Kramers–Smoluchowski model. The comparison of results in different solvents clearly indicates the importance of reactant–solvent cluster formation modifying the height and imaginary frequency of the barrier. The change of the temperature dependence with pressure points towards a multidimensional barrier of nonseparable character. Multidimensional barrier effects manifest themselves most clearly via the temperature dependence of the rate coefficient in the Kramers–Smoluchowski limit. [ABSTRACT FROM AUTHOR]

The photoisomerization of diphenylbutadiene was studied by picosecond absorption spectroscopy over wide pressure and temperature ranges in liquid and supercritical alkanes, CO2, SF6, and He. The reaction shows typical features of a thermal unimolecular reaction on the S1 potential energy surface. The rate can be expressed by a combination of standard unimolecular rate theory and Kramers–Smoluchowski theory. However, multidimensional behavior manifests itself in the transition to the gas phase low pressure range as well as to the high density Kramers–Smoluchowski range: in the former case, the low pressure limit of a unimolecular reaction of the polyatomic molecule is approached; in the latter case, the effective imaginary barrier frequency shows a marked apparent temperature dependence. The experiments also suggest contributions of reactant–solvent cluster interactions, which modify the barrier height even in nonpolar solvents. [ABSTRACT FROM AUTHOR]

Immunosuppression after Heart transplantation (HTx) carries a life-long risk for infection and reactivation of herpesviridae. Especially changes in the immunosuppressive therapy regime can promote viral reactivation. Infections with SARS-CoV-2 can also alter the immune response. However, potential effects on herpesviridae reactivation still needs to be examined in this context. Since emerge of the COVID-19 pandemic in the early 2020, n=61 of our HTx or heart and kidney transplant (HKTx) patients had positive polymerase chain reaction (PCR) for SARS-CoV-2. Relevant patient data including results for potential concomitant herpes simplex virus (HSV-1, HSV-2), cytomegalovirus (CMV), Epstein-Barr-virus (EBV), varicella zoster virus (CZV) and human herpesvirus-8 (HHV-8) DNAemia were retrospectively reviewed in September 2022 to evaluate its clinical impact. Most patients have received at least one and up to six doses of COVID-19 vaccine before contracting SARS-CoV-2. In general, HTx and HKTx patients developed symptomatic but mild COVID-19, which was most likely caused by any kind of omicron subvariant. SARS-CoV-2 positive HTx and HKTx patients were pharmacologically treated for COVID-19. DNAemia of herpesviridae was examined in about one third of the patients (n=20). HSV-1 DNAemia was confirmed in 6.25% of tested patients with a maximum viral load of 1,130,000 HSV-1-DNA copies/µg-DNA. In not a single patient HSV-2, VZV and HHV-8 DNA was found. In contrast, CMV was observed in 20% of tested patients with a maximum of 195 CMV-DNA copies/µg-DNA and EBV in 23.5% (maximum 1230 EBV-DNA copies/µg-DNA). In one patient simultaneous CMV- and EBV-DNAemia and in another patient EBV- and HSV-1-DNAemia were found. Nevertheless, none of these patients developed clinically relevant infection or reactivation of herpesviridae and therefore no targeted treatment was initiated. Recently, SARS-CoV-2 infections are commonly observed in patients after HTx and HKTx. Fortunately, patients rarely suffer from severe COVID-19-related symptoms. Meanwhile, concomitant infections or reactivation of herpesviridae, especially CMV and EBV, are regularly observed. Although we did not overserved CMV or EBV disease, regularly testing for herpesviridae seems reasonable in these patients. [ABSTRACT FROM AUTHOR]

Background:Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours.Methods:Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course.Results:Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of ∼135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile.Conclusions:These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients. [ABSTRACT FROM AUTHOR]

The Yakima River Basin (Basin) in south-central Washington is a prime example of a place where competing water uses, coupled with over-allocation of water resources, have presented water managers with the challenge of meeting current demand, anticipating future demand, and preparing for potential impacts of climate change. We took a decision analysis approach that gathered diverse stakeholders to discuss their concerns pertaining to climate change effects on the Basin and future goals that were collectively important. One main focus was centered on how climate change may influence future salmon populations. Salmon have played a prominent role in the cultures of Basin communities, especially for tribal communities that have social, cultural, spiritual, subsistence, and economic ties to them. Stakeholders identified the need for a better understanding on how the cultural, spiritual, subsistence, and economic aspects of the Confederated Tribes and Bands of the Yakama Nation could be affected by changes in salmon populations. In an attempt to understand the complexities of these potential effects, this paper proposes a conceptual model which 1) identifies cultural values and components and the interactions between those components that could influence tribal well-being, and 2) shows how federal natural resource managers could incorporate intangible tribal cultural components into decision-making processes by understanding important components of tribal well-being. Future work includes defining the parameterization of the cultural components in order for the conceptual model to be incorporated with biophysical resource models for scenario simulations. [ABSTRACT FROM AUTHOR]

Designing climate-related research so that study results will be useful to natural resource managers is a unique challenge. While decision makers increasingly recognize the need to consider climate change in their resource management plans, and climate scientists recognize the importance of providing locally-relevant climate data and projections, there often remains a gap between management needs and the information that is available or is being collected. We used decision analysis concepts to bring decision-maker and stakeholder perspectives into the applied research planning process. In 2009 we initiated a series of studies on the impacts of climate change in the Yakima River Basin (YRB) with a four-day stakeholder workshop, bringing together managers, stakeholders, and scientists to develop an integrated conceptual model of climate change and climate change impacts in the YRB. The conceptual model development highlighted areas of uncertainty that limit the understanding of the potential impacts of climate change and decision alternatives by those who will be most directly affected by those changes, and pointed to areas where additional study and engagement of stakeholders would be beneficial. The workshop and resulting conceptual model highlighted the importance of numerous different outcomes to stakeholders in the basin, including social and economic outcomes that go beyond the physical and biological outcomes typically reported in climate impacts studies. Subsequent studies addressed several of those areas of uncertainty, including changes in water temperatures, habitat quality, and bioenergetics of salmonid populations. [ABSTRACT FROM AUTHOR]

During the past decades large-scale models have been developed to simulate global and continental terrestrial water cycles. It is an open question whether these models are suitable to capture hydrological drought, in terms of runoff, on a global scale. A multimodel ensemble analysis was carried out to evaluate if 10 such large-scale models agree on major drought events during the second half of the twentieth century. Time series of monthly precipitation, monthly total runoff from 10 global hydrological models, and their ensemble median have been used to identify drought. Temporal development of area in drought for various regions across the globe was investigated. Model spread was largest in regions with low runoff and smallest in regions with high runoff. In vast regions, correlation between runoff drought derived from the models and meteorological drought was found to be low. This indicated that models add information to the signal derived from precipitation and that runoff drought cannot directly be determined from precipitation data alone in global drought analyses with a constant aggregation period. However, duration and spatial extent of major drought events differed between models. Some models showed a fast runoff response to rainfall, which led to deviations from reported drought events in slowly responding hydrological systems. By using an ensemble of models, this fast runoff response was partly overcome and delay in drought propagating from meteorological drought to drought in runoff was included. Finally, an ensemble of models also allows for consideration of uncertainty associated with individual model structures. [ABSTRACT FROM AUTHOR]

Climate change is expected to alter the hydrological cycle resulting in large-scale impacts on water availability. However, future climate change impact assessments are highly uncertain. For the first time, multiple global climate (three) and hydrological models (eight) were used to systematically assess the hydrological response to climate change and project the future state of global water resources. This multi-model ensemble allows us to investigate how the hydrology models contribute to the uncertainty in projected hydrological changes compared to the climate models. Due to their systematic biases, GCM outputs cannot be used directly in hydrological impact studies, so a statistical bias correction has been applied. The results show a large spread in projected changes in water resources within the climate- hydrology modelling chain for some regions. They clearly demonstrate that climate models are not the only source of uncertainty for hydrological change, and that the spread resulting from the choice of the hydrology model is larger than the spread originating from the climate models over many areas. But there are also areas showing a robust change signal, such as at high latitudes and in some midlatitude regions, where the models agree on the sign of projected hydrological changes, indicative of higher confidence in this ensemble mean signal. In many catchments an increase of available water resources is expected but there are some severe decreases in Central and Southern Europe, the Middle East, the Mississippi River basin, southern Africa, southern China and south-eastern Australia. [ABSTRACT FROM AUTHOR]

The 12C(α, γ)16O reaction is one of the most important in nuclear astrophysics since it determines the ratio of 12C to 16O during stellar helium burning. Experimental data, however, are still subject to large uncertainties due to the almost vanishing cross section at stellar energies. So far, most measurements have been performed with germanium detectors. To compensate for their low efficiency, the highest beam currents had to be used, resulting in target degradation and beam-induced backgrounds. Instead, the present measurement was performed with high-efficiency detectors and low beam currents, using the Karlsruhe 4π BaF2 detector and the pulsed 3.7-MV Van de Graaff accelerator at Karlsruhe Institute of Technology. The 12C(α, γ)16O cross sections have been measured at center-of-mass energies E between 1002 and 1510 keV, and the E1 and E2 components were derived with an accuracy comparable to the previous best data obtained with HPGe detectors. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effect of climate change on available water resources using hydrology and multiple global climate models. It states that a large spread of climate change projection in water resources in the climate-hydrology modeling chain. It concludes that the impact of climate change does not only rely on climate models and emission scenarios.

Abstract: An 60Fe target for studying the 60Fe(n, γ)61Fe cross-section at stellar energies was prepared using radio-chemical separation techniques. In total, 7.8×1015 60Fe atoms (777ng) were separated from a copper beam dump for the 590MeV proton beam of the high intensity accelerator at PSI. The final target was prepared by evaporating the iron-containing aqueous solution onto a graphite backing. With this sample the keV neutron capture cross-section of 60Fe has been measured at FZ Karlsruhe. The work is part of the ERAWAST-initiative (Exotic Radionuclides from Accelerator WAste for Science and Technology) which is aimed at extracting rare valuable radionuclides from accelerator waste by chemical means. [Copyright &y& Elsevier]

Abstract: A high power target for neutron production has been developed for the upcoming intense neutron source FRANZ at the University of Frankfurt. At this facility neutrons will be produced via the 7Li(p,n)7Be reaction by bombarding layers of a high temperature Li compound with pulsed proton beams of up to 2mA average current and maximum energies of 2.3MeV. Cooling is achieved by water flowing under high pressure through capillaries in a 1.2mm thick copper target. The heat distribution has been calculated with the fluid dynamics code StarCD/3.26, ensuring that the copper surface remains below at the maximum beam power of 5kW. The moderating effect of the cooling water on the neutron spectra was studied by simulations using the GEANT software package. A prototype target was successfully tested at the Karlsruhe Van de Graaff accelerator, confirming stable operation at a thermal load of 5kW/cm2. [Copyright &y& Elsevier]

Modern dual chamber ICD systems are able to overcome various sensing problems. However, improvement of their performance is still required. The aim of this study was to assess the sensing function in 101 consecutive patients (84 men, 17 women; mean age 63 +/- 12 years; mean follow-up 24 +/- 4 months) implanted with dual chamber defibrillators and integrated (IB) or dedicated bipolar (DB) lead systems. Follow-up data were analyzed for the presence of ventricular oversensing. Oversensing occurred in 25 (25%) patients, significantly more frequent in patients implanted with IB compared to DB lead systems (21/52 vs 4/49, P = 0.0002). Patients with cardiomyopathies (CMs) were more prone to sensing malfunctions than patients with no CM (12/30 vs 13/71, P = 0.04). T wave oversensing (n = 14), respirophasic ventricular oversensing (n = 4), and P wave oversensing (n = 6) were the most common pitfalls of ventricular sensing. P wave oversensing was unique to the IB lead system. CT scans performed in these patients disclosed the position of the RV coil to be proximal to the tricuspid area. Four patients received inappropriate ICD shocks due to oversensing. In all but two patients who received lead revision, oversensing was resolved by noninvasive means. In conclusion: (1) ventricular oversensing is a common problem occurring in up to 25% of patients with dual chamber ICDs; (2) P wave oversensing is a ventricular sensing problem affecting function of 11% of dual chamber devices with IB lead systems; (3) IB leads are significantly more susceptible to T wave and P wave oversensing than DB leads; and (4) patients with cardiomyopathies are more prone to oversensing than patients with other heart diseases. [ABSTRACT FROM AUTHOR]