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Study Region Kachemak Bay is a fjord-type estuary in the northern Gulf of Alaska. Water quality and habitat characteristics are strongly influenced by freshwater and sediment input from multiple glacierized catchments. Study Focus We present a new method combining imaging spectroscopy from an airborne survey with Landsat and Sentinel-2 imagery to map water surface turbidity originating from glacial runoff based on spectral abundance. We compare the spectral characteristics of turbid glacial water to clear water and generate a high resolution reference map of glacial turbidity in Kachemak Bay. This informs the subsequent analysis of a homogenized, Rayleigh corrected time series of Landsat and Sentinel-2 images and seasonal patterns of turbidity. New Hydrological Insights for the Region Our results provide the most comprehensive data set on water surface turbidity in Kachemak Bay to date and improve understanding of spatial and seasonal variability of glacial turbidity in a data sparse region. July and August have the largest plumes with median sizes around 150 km 2 , or around a quarter of Kachemak Bay. Plume sizes typically decrease with decreasing glacier runoff in September and October. We show that imaging spectroscopy aids assessments of turbid water in glacial marine catchments across scales. Leveraging high resolution spectral information allows for water color analyses that are customized to local conditions and catchment characteristics as well as scalable to wider regions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lea Hartl reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

X-ray sources for a range of wavelengths are being considered for in situ calibration of X-ray Imaging Crystal Spectrometers (XICSs) and for monitoring line shifts due to changes in the crystal temperature, which can vary during experimental operation over a day [A. Ince-Cushman et al., Rev. Sci. Instrum. 79, 10E302 (2008), L. Delgado-Aparicio et al., Plasma Phys. Control. Fusion 55, 125011 (2013)]. Such crystal temperature dependent shifts, if not accounted for, could be erroneously interpreted as Doppler shifts leading to errors in plasma flow-velocity measurements. The x-ray sources encompass characteristic x-ray lines falling within the wavelength range of 0.9-4.0 Å, relevant for the XICSs on present and future fusion devices. Several technological challenges associated with the development of x-ray sources for in situ calibration are identified and are being addressed in the design of multiple x-ray tubes, which will be installed inside the spectrometer housing of the XICS for the JT-60SA tokamak. These x-ray sources will be especially useful for in situ calibration between plasma discharges. In this paper, laboratory experiments are described that were conducted with a Cu x-ray source, a heated quartz (102) crystal, and a pixelated Pilatus detector to measure the temperature dependent shifts of the Cu Kα1 and Kα2 lines at 1.5405 and 1.5443 Å, respectively, and to evaluate the 2d-lattice constant for the Bragg reflecting crystal planes as a function of temperature, which, in the case of in situ wavelength calibration, would have to be used for numerical analysis of the x-ray spectra from the plasma., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Generation of second-harmonic waves is one of the universal nonlinear phenomena that have found numerous technical applications in many modern technologies, in particular, in photonics. This phenomenon also has great potential in the field of magnonics, which considers the use of spin waves in magnetic nanostructures to implement wave-based signal processing and computing. However, due to the strong frequency dependence of the phase velocity of spin waves, resonant phase-matched generation of second-harmonic spin waves has not yet been achieved in practice. Here, we show experimentally that such a process can be realized using a combination of different modes of nano-sized spin-wave waveguides based on low-damping magnetic insulators. We demonstrate that our approach enables efficient spatially-extended energy transfer between interacting waves, which can be controlled by the intensity of the initial wave and the static magnetic field., (© 2024. The Author(s).)

Dytiscus latissimus (Coleoptera Dytiscidae) is an endangered diving beetle throughout its range. It is one of the two species of Dytiscidae listed in Annex II of the Habitats Directive, IUCN red list and in many national level legislations and therefore strictly protected. The conservation of endangered species first of all requires an assessment of their population size. Until now, a method has not been developed for estimating the size of D. latissimus populations. The article summarizes the results of two studies carried out independently in Germany and Latvia. Both studies were carried out in one water body used recapture method but with a different spatial placement of traps, which, according to our data, is an important factor in population estimation. We evaluated Jolly-Seber and Schnabel approaches of estimating aquatic beetle's populations and found that confidence intervals obtained by different methods in our research do not differ significantly, but combination of both models provide the most accurate estimates of population dynamics. As part of the study, we concluded that the populations of Dytiscus latissimus are relatively closed, so we accept that the Schnabel estimate shows more accurate data. By fixing the places of capture of each individual, it was found that females live mainly locally, and males actively move within the water body. This aspect indicates the advantage of the spatial placement of traps compared to the use of transects. The results of our study show a significantly higher number of both captured and recaptured males Such a sex ratio may indicate both a greater activity of males and differences in the sex ratio in the population. The study confirmed that environmental changes, such as the water level in a water body, can also significantly affect the result of a population assessment. In the frame of D. latissimus monitoring, to obtain an objective estimation of the species population size we recommend using four traps for each 100 m of water body shoreline with 4-8 censuses, dependently on the recapture rate., (© 2023. The Author(s).)

Purpose: To investigate whether a training program on breast ultrasound skills including core-needle biopsies to undergraduate students can improve medical knowledge and learning satisfaction., Methods: Medical students attending mandatory classes at the Medical School of the University of Saarland received a supplemental theoretical and hands-on training program on ultrasound (US) breast screening and on US-guided core-needle biopsy using an agar-agar phantom. Experienced breast specialists and ultrasound examiners served as trainers applying Peyton's 4-step training approach. The students' theoretical knowledge and hands-on skills were tested before and after the training program, using a multiple-choice questionnaire (MCQ), the Objective Structured Clinical Examination (OSCE) and a student curriculum evaluation., Results: The MCQ results showed a significant increase of the student's theoretical knowledge (50.2-75.2%, p < 0.001). After the course, the OSCE showed a mean total of 17.3/20 points (86.5%), confirming the practical implementation of the new skills. The student curriculum evaluation in general was very positive. A total of 16/20 questions were rated between 1.2 and 1.7 (very good) and 3 questions were rated as 2.1 (good)., Conclusion: Undergraduate student's medical education can be enhanced by teaching breast US skills.

Delta-E effect sensors are based on magnetoelectric resonators that detune in a magnetic field due to the delta-E effect of the magnetostrictive material. In recent years, such sensors have shown the potential to detect small amplitude and low-frequency magnetic fields. Yet, they all require external magnetic bias fields for optimal operation, which is highly detrimental to their application. Here, we solve this problem by combining the delta-E effect with exchange biased multilayers and operate the resonator in a low-loss torsion mode. It is comprehensively analyzed experimentally and theoretically using various kinds of models. Due to the exchange bias, no external magnetic bias fields are required, but still low detection limits down to [Formula: see text] at 25 Hz are achieved. The potential of this concept is demonstrated with a new operating scheme that permits simultaneous measurement and localization, which is especially desirable for typical biomedical inverse solution problems. The sensor is localized with a minimum spatial resolution of 1 cm while measuring a low-frequency magnetic test signal that can be well reconstructed. Overall, we demonstrate that this class of magnetic field sensors is a significant step towards first biomedical applications and compact large number sensor arrays.

Background: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb)., Methods: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed., Results: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure., Conclusion: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.

Background: Laparoscopic liver resections (LLR) have been increasingly performed in recent years. Most of the available evidence, however, comes from specialized centers in Asia, Europe and USA. Data from South America are limited and based on single-center experiences. To date, no multicenter studies evaluated the results of LLR in South America. The aim of this study was to evaluate the experience and results with LLR in South American centers., Methods: From February to November 2019, a survey about LLR was conducted in 61 hepatobiliary centers in South America, composed by 20 questions concerning demographic characteristics, surgical data, and perioperative results., Results: Fifty-one (83.6%) centers from seven different countries answered the survey. A total of 2887 LLR were performed, as follows: Argentina (928), Brazil (1326), Chile (322), Colombia (210), Paraguay (9), Peru (75), and Uruguay (8). The first program began in 1997; however, the majority (60.7%) started after 2010. The percentage of LLR over open resections was 28.4% (4.4-84%). Of the total, 76.5% were minor hepatectomies and 23.5% major, including 266 right hepatectomies and 343 left hepatectomies. The conversion rate was 9.7%, overall morbidity 13%, and mortality 0.7%., Conclusions: This is the largest study assessing the dissemination and results of LLR in South America. It showed an increasing number of centers performing LLR with the promising perioperative results, aligned with other worldwide excellence centers.

Integrated high-resolution maps of carbon stocks and biodiversity that identify areas of potential co-benefits for climate change mitigation and biodiversity conservation can help facilitate the implementation of global climate and biodiversity commitments at local levels. However, the multi-dimensional nature of biodiversity presents a major challenge for understanding, mapping and communicating where and how biodiversity benefits coincide with climate benefits. A new integrated approach to biodiversity is therefore needed. Here, we (a) present a new high-resolution map of global above- and below-ground carbon stored in biomass and soil, (b) quantify biodiversity values using two complementary indices (BIp and BIr) representing proactive and reactive approaches to conservation, and (c) examine patterns of carbon-biodiversity overlap by identifying 'hotspots' (20% highest values for both aspects). Our indices integrate local diversity and ecosystem intactness, as well as regional ecosystem intactness across the broader area supporting a similar natural assemblage of species to the location of interest. The western Amazon Basin, Central Africa and Southeast Asia capture the last strongholds of highest local biodiversity and ecosystem intactness worldwide, while the last refuges for unique biological communities whose habitats have been greatly reduced are mostly found in the tropical Andes and central Sundaland. There is 38 and 5% overlap in carbon and biodiversity hotspots, for proactive and reactive conservation, respectively. Alarmingly, only around 12 and 21% of these proactive and reactive hotspot areas, respectively, are formally protected. This highlights that a coupled approach is urgently needed to help achieve both climate and biodiversity global targets. This would involve (1) restoring and conserving unprotected, degraded ecosystems, particularly in the Neotropics and Indomalaya, and (2) retaining the remaining strongholds of intactness. This article is part of the theme issue 'Climate change and ecosystems: threats, opportunities and solutions'.

Purpose: Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR., Methods: Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3 months, was measured at birth., Results: 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]., Conclusion: Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied., Trial Registration: Clinical trial registration: NCT03389178.

Objective: To compare the efficacy and safety of two post-operative drains in breast cancer patients after breast conserving surgery., Methods: This was a prospectively randomized comparative study of two drains investigated in breast cancer patients after breast conserving therapy. The Redon drain ends in a tip with 28 double perforations while the Quadrain drain features 4 flexible flaps of about 0.15 m length. The drains cost 0.28 € and 3.54 €, respectively. Primary target parameter was the duration of the drains staying in the surgical site. Secondary target parameters were pain post-surgery, seroma volume, final cosmetic result and surgical site infections., Results: A total of 88 patients were randomized, 47 and 41 received the Redon drain and the Quadrain drain, respectively. The mean duration of the drains staying in the surgical site was not different between the Redon and the Quadrain drain, 42.6 h (± 25.8 h) and 50.1 h (± 28.5 h), respectively (p = 0.1959). The post-operative pain score, seroma size, cosmetic result and surgical site infections were not different for both systems., Conclusion: The Redon drain and the new Quadrain drain were not significantly different with respect to duration in the surgical site, post-operative pain, seroma volume and cosmetic result.

Background: In Germany, physicians who prescribe cannabis-based medicines at the expense of the statutory health insurance are obliged to take part in an accompanying survey. Pain was the most commonly reported diagnosis, making an interim evaluation for the indication of pain feasible., Methods: Patient-related data was transmitted to the German Federal Institute for Drugs and Medical Devices via an online portal. In addition to demographic data, information on the treated disease or symptoms, the course of therapy, adverse reactions and treatment success were evaluated., Results: A total of 3138 data sets were evaluated for the main diagnosis of pain. Dronabinol was the most frequently (64%) prescribed cannabis-based drug. On average, patients were 57 years old and women and men were equally represented. Patients treated with cannabis flowers were significantly younger (48 years). The proportion of men in this group was 68% and 83% in the group of 18- to 40-year-olds. According to the assessment by treating physicians, pain was significantly improved in 35.5% of the patients. The most frequent side effects (fatigue, dizziness, nausea) corresponded to those already known from the product information of the cannabis-based medicinal products authorized under the pharmaceutical law. Treatment was discontinued in 1179 patients within 1 year., Conclusion: Physicians should comply with their legal obligation to participate in the accompanying survey. Pain is by far the most common diagnosis in cannabis drugs. For about one third of these patients, physicians reported a clear improvement in pain. Due to the amount of data hitherto and the limitations in the accompanying survey, the results should not be overinterpreted in terms of efficacy and should always be related to existing reviews. The lower age and higher proportion of men among patients treated with cannabis flowers were remarkable. At 37.6%, the overall drop-out rate was high. The most frequent side effects related to vigilance and are therefore highly relevant in terms of driving ability, work ability and risk of falling. For a differentiated evaluation of treatment success, more data needs to be available.

Objectives: Maternal gestational diabetes mellitus (GDM) is known to influence fetal physiology. Phase-rectified signal averaging (PRSA) is an innovative signal-processing technique that can be used to investigate fetal heart signals. The PRSA-calculated variables average acceleration capacity (AAC) and average deceleration capacity (ADC) are established indices of autonomic nervous system (ANS) function. The aim of this study was to evaluate the influence of GDM on the fetal cardiovascular and ANS function in human pregnancy using PRSA., Methods: This was a prospective clinical case-control study of 58 mothers with diagnosed GDM and 58 gestational-age matched healthy controls in the third trimester of pregnancy. Fetal cardiotocography (CTG) recordings were performed in all cases at entry to the study, and a follow-up recording was performed in 19 GDM cases close to delivery. The AAC and ADC indices were calculated by the PRSA method and fetal heart rate short-term variation (STV) by CTG software according to Dawes-Redman criteria., Results: Mean gestational age of both groups at study entry was 35.7 weeks. There was a significant difference in mean AAC (1.97 ± 0.33 bpm vs 2.42 ± 0.57 bpm; P < 0.001) and ADC (1.94 ± 0.32 bpm vs 2.28 ± 0.46 bpm; P < 0.001) between controls and fetuses of diabetic mothers. This difference could not be demonstrated using standard computerized fetal CTG analysis of STV (controls, 10.8 ± 3.0 ms vs GDM group, 11.3 ± 2.5 ms; P = 0.32). Longitudinal fetal heart rate measurements in a subgroup of women with diabetes were not significantly different from those at study entry., Conclusions: Our findings show increased ANS activity in fetuses of diabetic mothers in late gestation. Analysis of human fetal cardiovascular and ANS function by PRSA may offer improved surveillance over conventional techniques linking GDM pregnancy to future cardiovascular dysfunction in the offspring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Introduction: This is a state-of-the-art article of the diagnostic process, etiologies and management of acute right ventricular (RV) failure in critically ill patients. It is based on a large review of previously published articles in the field, as well as the expertise of the authors., Results: The authors propose the ten key points and directions for future research in the field. RV failure (RVF) is frequent in the ICU, magnified by the frequent need for positive pressure ventilation. While no universal definition of RVF is accepted, we propose that RVF may be defined as a state in which the right ventricle is unable to meet the demands for blood flow without excessive use of the Frank-Starling mechanism (i.e. increase in stroke volume associated with increased preload). Both echocardiography and hemodynamic monitoring play a central role in the evaluation of RVF in the ICU. Management of RVF includes treatment of the causes, respiratory optimization and hemodynamic support. The administration of fluids is potentially deleterious and unlikely to lead to improvement in cardiac output in the majority of cases. Vasopressors are needed in the setting of shock to restore the systemic pressure and avoid RV ischemia; inotropic drug or inodilator therapies may also be needed. In the most severe cases, recent mechanical circulatory support devices are proposed to unload the RV and improve organ perfusion CONCLUSION: RV function evaluation is key in the critically-ill patients for hemodynamic management, as fluid optimization, vasopressor strategy and respiratory support. RV failure may be diagnosed by the association of different devices and parameters, while echocardiography is crucial.

Aim: Most deaths after myocardial infarction (MI) occur in patients with normal or moderately reduced left ventricular ejection fraction (LVEF >35%). Periodic repolarization dynamics (PRD) and deceleration capacity (DC) are novel ECG-based markers related to sympathetic and vagal cardiac autonomic nervous system activity. Here, we test the combination of PRD and DC to predict risk in post-infarction patients with LVEF >35%., Methods and Results: We included 823 survivors of acute MI with LVEF >35%, aged ≤80years and in sinus rhythm. PRD and DC were obtained from 30-min ECG-recordings within the second week after index infarction and dichotomized at established cut-off values of ≥5.75deg 2 and ≤2.5ms, respectively. Patients were classified as having normal (CAF 0), partly abnormal (DC or PRD abnormal; CAF 1) or abnormal cardiac autonomic function (DC and PRD abnormal; CAF 2). Primary endpoint was 5-year all-cause mortality. Within the first 5years of follow-up, 51 patients died (6.2%). PRD and DC effectively stratified patients into low-risk (CAF 0; n=562), intermediate-risk (CAF 1; n=193) and high-risk patients (CAF 2; n=68) with cumulative 5-year mortality rates of 2.9%, 9.4% and 25.2%, respectively (p<0.001). On multivariable analyses, CAF was independent from established risk factors (GRACE-score, diabetes mellitus, mean heart rate, heart rate variability). Addition of CAF significantly improved the model (increase of C-statistics from 0.732 (0.651-0.812) to 0.777 (0.703-0.850), p=0.047; continuous NRI (0.400, 95% CI 0.230-0.560, p<0.001); IDI (0.056, 95% CI 0.022-0.122, p<0.001))., Conclusion: CAF identifies new high-risk post-MI patients with LVEF >35% which might benefit from prophylactic strategies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The initial therapy of chronic heart failure is still based on diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and in specific cases mineralocorticoid receptor antagonists. The new European Society of Cardiology (ESC) guidelines published in 2016 introduced angiotensin-receptor-neprilysin inhibitors, such as sacubitril/valsartan (LCZ 696) as new therapeutic agents in patients with chronic and progressive heart failure. New subgroup analyses for LCZ 696 have been published showing a beneficial effect in the context of various comorbidities, such as renal insufficiency, diabetes and hypotension. Furthermore, new data are available on intravenous iron substitution in chronic heart failure and on the indications for implantable converter defibrillators, cardiac resynchronization therapy and other cardiac devices. Medicinal therapy of acute heart failure is still limited. For patients who cannot be treated with medicinal therapy, mechanical circulatory support, such as extracorporeal membrane oxygenation (ECMO) should be recommended.

Background: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies., Patients and Methods: Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification., Results: We demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of β-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of β-catenin. Analysis of all patients with activating Wnt/β-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion., Conclusions: The PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/β-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies., Clinical Trials.gov Identifier: NCT02022371., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Nonsyndromic cleft palate only (nsCPO) is a facial malformation that has a livebirth prevalence of 1 in 2,500. Research suggests that the etiology of nsCPO is multifactorial, with a clear genetic component. To date, genome-wide association studies have identified only 1 conclusive common variant for nsCPO, that is, a missense variant in the gene grainyhead-like-3 ( GRHL3). Thus, the underlying genetic causes of nsCPO remain largely unknown. The present study aimed at identifying rare variants that might contribute to nsCPO risk, via whole-exome sequencing (WES), in multiply affected Central European nsCPO pedigrees. WES was performed in 2 affected first-degree relatives from each family. Variants shared between both individuals were analyzed for their potential deleterious nature and a low frequency in the general population. Genes carrying promising variants were annotated for 1) reported associations with facial development, 2) multiple occurrence of variants, and 3) expression in mouse embryonic palatal shelves. This strategy resulted in the identification of a set of 26 candidate genes that were resequenced in 132 independent nsCPO cases and 623 independent controls of 2 different ethnicities, using molecular inversion probes. No rare loss-of-function mutation was identified in either WES or resequencing step. However, we identified 2 or more missense variants predicted to be deleterious in each of 3 genes ( ACACB, PTPRS, MIB1) in individuals from independent families. In addition, the analyses identified a novel variant in GRHL3 in 1 patient and a variant in CREBBP in 2 siblings. Both genes underlie different syndromic forms of CPO. A plausible hypothesis is that the apparently nonsyndromic clefts in these 3 patients might represent hypomorphic forms of the respective syndromes. In summary, the present study identified rare variants that might contribute to nsCPO risk and suggests candidate genes for further investigation.

Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1-a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT-on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer's disease. Systemic administration of JQ1 elicited a hippocampal gene expression program that is associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory.

Purpose: Critical care ultrasonography has utility for the diagnosis and management of critical illness and is in widespread use by frontline intensivists. As there is a need for research to validate and extend its utility, the Editor of Intensive Care Medicine included critical care ultrasonography as a topic in the ICM Research Agenda issue., Methods: Eleven international experts in the field of critical care ultrasonography contributed to the writing project. With the intention of developing a research agenda for the field, they reviewed best standards of care, new advances in the field, common beliefs that have been contradicted by recent trials, and unanswered questions related to critical care ultrasonography., Results: The writing group focused on the provision of training in critical care ultrasonography, technological advances, and some specific clinical applications., Conclusions: The writing group identified several fields of interest for research and proposed ten research studies that would address important aspects of critical care ultrasonography.

The resistance of the electron gas (2DEG) at the interface between the two band insulators LaAlO 3 (LAO) and SrTiO 3 (STO) typically drops monotonically with temperature and R/T curves during cooling and warm-up look identical for large area structures. Here we show that if the LAO/STO is laterally restricted by nanopatterning the resistance exhibits a temperature anomaly. Warming up nanostructures from low temperatures leads to one or two pronounced resistance peaks between 50 and 100 K not observed for larger dimensions. During cool-down current filaments emerge at the domain walls that form during a structural phase transition of the STO substrate. During warm-up the reverse phase transition can interrupt filaments before the sheet conductivity which dominates at higher temperature is reestablished. Due to the limited number of filaments in a nanostructure this process can result in a complete loss of conductance. As a consequence of these findings the transport physics extracted from experiments in small and large area LAO/STO structures may need to be reconsidered.