Domain and Geometry Agnostic CNNs for Left Atrium Segmentation in 3D Ultrasound

Segmentation of the left atrium and deriving its size can help to predict and detect various cardiovascular conditions. Automation of this process in 3D Ultrasound image data is desirable, since manual delineations are time-consuming, challenging and observer-dependent. Convolutional neural networks have made improvements in computer vision and in medical image analysis. They have successfully been applied to segmentation tasks and were extended to work on volumetric data. In this paper we introduce a combined deep-learning based approach on volumetric segmentation in Ultrasound acquisitions with incorporation of prior knowledge about left atrial shape and imaging device. The results show, that including a shape prior helps the domain adaptation and the accuracy of segmentation is further increased with adversarial learning

Parallelism and Epistasis in Skeletal Evolution Identified through Use of Phylogenomic Mapping Strategies

The identification of genetic mechanisms underlying evolutionary change is critical to our understanding of natural diversity, but is presently limited by the lack of genetic and genomic resources for most species. Here, we present a new comparative genomic approach that can be applied to a broad taxonomic sampling of nonmodel species to investigate the genetic basis of evolutionary change. Using our analysis pipeline, we show that duplication and divergence of fgfr1a is correlated with the reduction of scales within fishes of the genus Phoxinellus. As a parallel genetic mechanism is observed in scale-reduction within independent lineages of cypriniforms, our finding exposes significant developmental constraint guiding morphological evolution. In addition, we identified fixed variation in fgf20a within Phoxinellus and demonstrated that combinatorial loss-of-function of fgfr1a and fgf20a within zebrafish phenocopies the evolved scalation pattern. Together, these findings reveal epistatic interactions between fgfr1a and fgf20a as a developmental mechanism regulating skeletal variation among fishes

Parabolic diamond scanning probes for single spin magnetic field imaging

Enhancing the measurement signal from solid state quantum sensors such as the nitrogen-vacancy (NV) center in diamond is an important problem for sensing and imaging of condensed matter systems. Here we engineer diamond scanning probes with a truncated parabolic profile that optimizes the photonic signal from single embedded NV centers, forming a high-sensitivity probe for nanoscale magnetic field imaging. We develop a scalable fabrication procedure based on dry etching with a flowable oxide mask to reliably produce a controlled tip curvature. The resulting parabolic tip shape yields a median saturation count rate of 2.1 $\pm$ 0.2 MHz, the highest reported for single NVs in scanning probes to date. Furthermore, the structures operate across the full NV photoluminescence spectrum, emitting into a numerical aperture of 0.46 and the end-facet of the truncated tip, located near the focus of the parabola, allows for small NV-sample spacings and nanoscale imaging. We demonstrate the excellent properties of these diamond scanning probes by imaging ferromagnetic stripes with a spatial resolution better than 50 nm. Our results mark a 5-fold improvement in measurement signal over the state-of-the art in scanning-probe based NV sensors.Comment: 8 pages, 6 figure

Childhood adversity and later life prosocial behavior: A qualitative comparative study of Irish older adult survivors

Objective Although childhood adversity can have lasting effects into later life, positive adaptations have also been observed, including an increased tendency toward prosocial behavior. However, little is known about the link between childhood adversity and later life prosocial behavior, with a particular scarcity of research on intrafamilial childhood adversity. Therefore, this study aimed to examine older adult's experiences of childhood adversity and identify mechanisms linked to prosocial behavior. Two adversity contexts (intrafamilial and extrafamilial) were compared to explore individual, as well as broader cultural and contextual mechanisms linking childhood adversity and later life prosocial behavior. Method Semi-structured interviews (60–120 min) were conducted with N = 29 Irish (older) adult survivors of childhood adversity: n = 12 intrafamilial survivors (mean age: 58 years, range: 51–72), n = 17 institutional survivors (mean age: 61 years, range: 50–77). Interviews were analyzed using the framework analysis method, with reference to the conceptual model of altruism born of suffering. Results Five themes were identified on prosocial mechanisms, with three themes in both survivor groups (enhanced empathy, self-identity, amelioration), and two group-specific themes (compassion fatigue in intrafamilial survivors; denouncing detrimental social values in institutional survivors). Conclusion Results identified motivational processes and volitional factors linked to later life prosocial behavior. Connections to caring roles, (lack of) support, and social norms in childhood, as well as the need for a sense of purpose and meaning from the adversities in adulthood, highlight potential targets for psychotherapeutic intervention to promote prosocial responding and positive adaptation for childhood adversity survivors

A socio-interpersonal perspective on the disclosure of childhood adversity: A qualitative comparative approach in Irish survivors

Childhood adversity (i.e., sexual, physical, or emotional abuse, and physical or emotional neglect) is a widespread, but often underreported, issue. While disclosure can be important for recovery, findings are inconsistent and often lack consideration of wider social and interpersonal contexts. This study aimed to examine disclosure in survivors of childhood adversity by applying a socio-interpersonal perspective. It further aimed to explore cultural and contextual influences on disclosure by assessing survivors from two distinct adversity contexts. Semi-structured interviews were conducted with 12 Irish survivors from an intrafamilial adversity context (mean age: 57.4 years, 11 females) and 17 Irish survivors from an institutional adversity context (mean age: 60.7 years, 10 females). Data was analyzed using framework analysis and the application of the socio-interpersonal model. Findings indicate unsuccessful and non-disclosure in childhood, with increased disclosure in adulthood. Themes identified shared disclosure-related factors (e.g., shame, inaction, lack of infrastructural and social support, societal acknowledgement); as well as context-specific findings (e.g., engrained family secret in the intrafamilial sample, power and influence of the church in the institutional sample). Results emphasize the necessity of considering not only the child-perpetrator relationship, but also the complex social, cultural, and interpersonal contexts within which the individual is embedded

Cryptic Variation in Morphological Evolution: HSP90 as a Capacitor for Loss of Eyes in Cavefish

In the process of morphological evolution, the extent to which cryptic, preexisting variation provides a substrate for natural selection has been controversial. We provide evidence that heat shock protein 90 (HSP90) phenotypically masks standing eye-size variation in surface populations of the cavefish Astyanax mexicanus. This variation is exposed by HSP90 inhibition and can be selected for, ultimately yielding a reduced-eye phenotype even in the presence of full HSP90 activity. Raising surface fish under conditions found in caves taxes the HSP90 system, unmasking the same phenotypic variation as does direct inhibition of HSP90. These results suggest that cryptic variation played a role in the evolution of eye loss in cavefish and provide the first evidence for HSP90 as a capacitor for morphological evolution in a natural setting

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

Case Report: Case Series of Children With Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Switzerland.

Since the beginning of the severe SARS-CoV-2 pandemic, an increasing number of countries reported cases of a systemic hyperinflammatory condition defined as multi-system inflammatory syndrome in children (MIS-C). The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), or have often an acute abdominal presentation. Intravenous immunoglobulin (IVIG) is recommended as first line therapy in KD. Recent evidence suggests intravenous immunoglobulins (IVIG) resistance in some cases of SARS-CoV-2 related MIS-C, thereby questioning the benefit of immunomodulators such as IL-1 or IL-6 blocking agents. We report on a cohort of 6 Swiss children with SARS-CoV2 related MIS-C presenting with clinical features compatible with Incomplete KD and Toxic Shock Syndrome associated to a cytokine storm. Serum cytokine profile investigations showed increased IL1RA levels (8 to 22-fold) in 5 of the 6 patients (one patient had not been tested), whereas, IL-6 serum levels were increased only in the 3 patients of the 6 who were tested. With exception of one patient who had only benefited by Anakinra, all patients received at least one dose of IVIG. One patient has only received Anakinra with favorable evolution, and three patients had also a steroid treatment. In addition to all this anti-inflammatory medication two patients have also received one dose of anti-IL6. In conclusion, our case series reports on clinical and laboratory findings of most of Swiss cases with MIS-C and suggests the use of Anakinra as an alternative to steroids in these children, most of whom presented with high IL-1RA levels

Diet-induced loss of adipose Hexokinase 2 triggers hyperglycemia

Chronically high blood glucose (hyperglycemia) leads to diabetes, fatty liver disease, and cardiovascular disease. Obesity is a major risk factor for hyperglycemia, but the underlying mechanism is unknown. Here we show that a high fat diet (HFD) in mice causes early loss of expression of the glycolytic enzyme Hexokinase 2 (HK2) specifically in adipose tissue. Adipose-specific knockout of Hk2 caused enhanced gluconeogenesis and lipogenesis in liver, a condition known as selective insulin resistance, leading to glucose intolerance. Furthermore, we observed reduced hexokinase activity in adipose tissue of obese and diabetic patients, and identified a loss-of-function mutation in the hk2 gene of naturally hyperglycemic Mexican cavefish. Mechanistically, HFD in mice led to loss of HK2 by inhibiting translation of Hk2 mRNA. Our findings identify adipose HK2 as a critical mediator of systemic glucose homeostasis, and suggest that obesity-induced loss of adipose HK2 is an evolutionarily conserved, non-cell-autonomous mechanism for the development of hyperglycemia