Maternal cell-free DNA-based screening for fetal microdeletion and the importance of careful diagnostic follow-up.

BackgroundNoninvasive prenatal screening (NIPS) by next-generation sequencing of cell-free DNA (cfDNA) in maternal plasma is used to screen for common aneuploidies such as trisomy 21 in high risk pregnancies. NIPS can identify fetal genomic microdeletions; however, sensitivity and specificity have not been systematically evaluated. Commercial companies have begun to offer expanded panels including screening for common microdeletion syndromes such as 22q11.2 deletion (DiGeorge syndrome) without reporting the genomic coordinates or whether the deletion is maternal or fetal. Here we describe a phenotypically normal mother and fetus who tested positive for atypical 22q deletion via maternal plasma cfDNA testing.MethodsWe performed cfDNA sequencing on saved maternal plasma obtained at 11 weeks of gestation from a phenotypically normal woman with a singleton pregnancy whose earlier screening at a commercial laboratory was reported to be positive for a 22q11.2 microdeletion. Fluorescence in situ hybridization and chromosomal microarray diagnostic genetic tests were done postnatally.ConclusionNIPS detected a 22q microdeletion that, upon diagnostic workup, did not include the DiGeorge critical region. Diagnostic prenatal or postnatal testing with chromosomal microarray and appropriate parental studies to determine precise genomic coordinates and inheritance should follow a positive microdeletion NIPS result

A survey of Sierra Nevada magmatism using Great Valley detrital zircon trace-element geochemistry: View from the forearc

The well-characterized Sierra Nevada magmatic arc offers an unparalleled opportunity to improve our understanding of continental arc magmatism, but present bedrock exposure provides an incomplete record that is dominated by Cretaceous plutons, making it challenging to decipher details of older magmatism and the dynamic interplay between plutonism and volcanism. Moreover, the forearc detrital record includes abundant zircon formed during apparent magmatic lulls, suggesting that understanding the long-term history of arc magmatism requires integrating plutonic, volcanic, and detrital records. We present trace-element geochemistry of detrital zircon grains from the Great Valley forearc basin to survey Sierra Nevadan arc magmatism through Mesozoic time. We analyzed 257 previously dated detrital zircon grains from seven sandstone samples of volcanogenic, arkosic, and mixed compositions deposited ca. 145–80 Ma along the length of the forearc basin. Detrital zircon trace-element geochemistry is largely consistent with continental arc derivation and shows similar geochemical ranges between samples, regardless of location along strike of the forearc basin, depositional age, or sandstone composition. Comparison of zircon trace-element data from the forearc, arc, and retroarc regions revealed geochemical asymmetry across the arc that was persistent through time and demonstrated that forearc and retroarc basins sampled different parts of the arc and therefore recorded different magmatic histories. In addition, we identified a minor group of Jurassic detrital zircon grains with oceanic geochemical signatures that may have provenance in the Coast Range ophiolite. Taken together, these results suggest that the forearc detrital zircon data set reveals information different from that gleaned from the arc itself and that zircon compositions can help to identify and differentiate geochemically distinct parts of continental arc systems. Our results highlight the importance of integrating multiple proxies to fully document arc magmatism, demonstrating that detrital zircon geochemical data can enhance understanding of a well-characterized arc, and these data may prove an effective means by which to survey an arc that is inaccessible and therefore poorly characterized

Assessment of a newly designed double-barreled bullet-shooting stunner for adequate stunning of water buffaloes

To ensure animal welfare at slaughter, rapid stunning is required to render the animal deeply unconscious. In cattle, captive-bolt stunners are typically used for this purpose. However, with regard to their impact force and maximum length of approximately 120 mm, such captive-bolt stunners are not suitable for stunning water buffaloes due to anatomical characteristics of the skull. In water buffaloes the bone layer is thicker and the distance from the point of attachment of the captive-bolt stunner to the relevant brain region is longer. For this reason, a special bullet-shooting stunner was developed, which is similar in size and handling to a standard captive-bolt stunner, but instead of a bolt, it fires a bullet. Actually, even two bullets can be loaded so that a follow-up shot can be fired immediately if necessary. In this study, the bullet-shooting stunner was tested using two different types of hunting ammunition for stunning water buffaloes during regular slaughter

BigBovid- Evaluation of a Newly Developed 9 mm Bullet-Shooting Stunner for Adequate Stunning of Heavy Cattle

The stunning of heavy cattle and water buffalo is an animal welfare problem, as conventional cartridge fired captive-bolt stunners are not suitable due to the thicker skull bones and the greater depth of penetration required to reach and damage the relevant brain regions for deep unconsciousness. This current animal welfare problem requires a suitable and feasible as well as commercially available and legally approved stunning device to ensure deep unconsciousness of these animals. In this study, the use of a newly developed bullet-shooting stunner, the BigBovid, with two different types of hunting ammunition, namely .38 SPL FMJ-TC and .357 MAG FTX ® bullets, was evaluated on 22 heavy cattle (mean weight: 1062.27 kg, standard deviation: 124.09 kg). In ballistic experiments, the BigBovid reached a mean energy density of 8.18 J/mm2 (mean error: 0.45 J/mm2) for the .38 SPL FMJ-TC and 17.56 J/mm2 (mean error: 2.67 J/mm2) for the .357 MAG FTX ®. In in vivo experiments, the use of the .38 SPL FMJ-TC resulted in overpenetration three times. The .357 MAG FTX ® bullets showed to be more advantageous, because on the one hand no overpenetration occurred and on the other hand the bullets fragmented into small parts after penetration into the skull. The fragments were scattered in the brain tissue, such as the thalamus and the brain stem, and thus there is a high probability to damage the brain regions relevant for deep unconsciousness. Based on the results of this study, the use of the BigBovid in combination with the .357 MAG FTX ® bullet is found to be suitable for stunning heavy cattle. Keywords: animal welfare; concussion; desensitization; heavy bulls; slaughterin

Tongue lacerations in children: to suture or not?

AIMS OF THE STUDY Tongue lacerations are common in children, occurring mostly from falls or sports injuries. Optimal treatment of tongue lacerations is a challenge for paediatricians due to contradictory recommendations and a lack of current guidelines. It remains unclear which tongue lacerations should be sutured and which would benefit from spontaneous healing, which is a promising alternative. In recent years, the treatment of choice in our paediatric emergency department (ED) has shifted from generally suturing the wounds to more frequently advising secondary wound healing. The aim of this study was to analyse tongue lacerations treated at our ED in order to develop guidance for the optimal management of tongue lacerations in children. METHODS This retrospective study was conducted to assess tongue lacerations at the ED of a University Children's Hospital Zurich from January 2010 to August 2015. All families were contacted for informed consent and photo documentation of the healed tongue. Clinical records of all the patients included were reviewed and different variables were defined and analysed. RESULTS A total of 73 children with tongue lacerations were included (75.3% boys, mean age ± standard deviation 4.0 ± 2.6 years). The mean size of the lacerations was 12.4 ± 8.3 mm, with affected tongue borders in 51 cases (69.9%) and a through-and-through laceration in 23 patients (31.5%). A primary wound closure was performed in 12 children (16.4%). These wounds were significantly larger than those of the secondary wound healing group (21 ± 10 mm compared to 10.8 ± 6.8 mm), presented gaping wound edges with the tongue at rest more frequently (91.7% compared to 32.8%), and showed through-and-through lacerations more often (91.7% compared to 19.7%). The group with wound suturing needed longer to recover (median 13 days compared to 6.2 days) and had a higher rate of complications (25 vs 3.3%). CONCLUSIONS Suturing is not required in gaping tongue lacerations less than 2 cm long that do not involve the tip of the tongue. The Zurich Tongue Scheme was developed as a guide for clinicians when deciding which tongue lacerations need suturing

Drosophila Activated Cdc42 Kinase Has an Anti-Apoptotic Function

Activated Cdc42 kinases (Acks) are evolutionarily conserved non-receptor tyrosine kinases. Activating somatic mutations and increased ACK1 protein levels have been found in many types of human cancers and correlate with a poor prognosis. ACK1 is activated by epidermal growth factor (EGF) receptor signaling and functions to regulate EGF receptor turnover. ACK1 has additionally been found to propagate downstream signals through the phosphorylation of cancer relevant substrates. Using Drosophila as a model organism, we have determined that Drosophila Ack possesses potent anti-apoptotic activity that is dependent on Ack kinase activity and is further activated by EGF receptor/Ras signaling. Ack anti-apoptotic signaling does not function through enhancement of EGF stimulated MAP kinase signaling, suggesting that it must function through phosphorylation of some unknown effector. We isolated several putative Drosophila Ack interacting proteins, many being orthologs of previously identified human ACK1 interacting proteins. Two of these interacting proteins, Drk and yorkie, were found to influence Ack signaling. Drk is the Drosophila homolog of GRB2, which is required to couple ACK1 binding to receptor tyrosine kinases. Drk knockdown blocks Ack survival activity, suggesting that Ack localization is important for its pro-survival activity. Yorkie is a transcriptional co-activator that is downstream of the Salvador-Hippo-Warts pathway and promotes transcription of proliferative and anti-apoptotic genes. We find that yorkie and Ack synergistically interact to produce tissue overgrowth and that yorkie loss of function interferes with Ack anti-apoptotic signaling. Our results demonstrate how increased Ack signaling could contribute to cancer when coupled to proliferative signals

Understanding and exploiting interfacial interactions between phosphonic acid functional groups and co-evaporated perovskites

Interfacial engineering has fueled recent development of p-i-n perovskite solar cells (PSCs), with self-assembled monolayer-based hole-transport layers (SAM-HTLs) enabling almost lossless contacts for solution-processed PSCs, resulting in the highest achieved power conversion efficiency (PCE) to date. Substrate interfaces are particularly crucial for the growth and quality of co-evaporated PSCs. However, adoption of SAM-HTLs for co-evaporated perovskite absorbers is complicated by the underexplored interaction of such perovskites with phosphonic acid functional groups. In this work, we highlight how exposed phosphonic acid functional groups impact the initial phase and final bulk crystal structures of co-evaporated perovskites and their resultant PCE. The explored surface interaction is mediated by hydrogen bonding with interfacial iodine, leading to increased formamidinium iodide adsorption, persistent changes in perovskite structure, and stabilization of bulk α-FAPbI3, hypothesized as being due to kinetic trapping. Our results highlight the potential of exploiting substrates to increase control of co-evaporated perovskite growth

Why Adverse Outcome Pathways Need to be FAIR

Adverse outcome pathways (AOPs) provide evidence for demonstrating and assessing causality between measurable toxicological mechanisms and human or environmental adverse effects. AOPs have gained increasing attention over the past decade and are believed to provide the necessary steppingstone for more effective risk assessment of chemicals and materials and moving beyond the need for animal testing. However, as with all types of data and knowledge today, AOPs need to be reusable by machines, i.e., machine-actionable, in order to reach their full impact potential. Machine-actionability is supported by the FAIR principles, which guide findability, accessibility, interoperability, and reusability of data and knowledge. Here, we describe why AOPs need to be FAIR and touch on aspects such as the improved visibility and the increased trust that FAIRification of AOPs provides.</p