Frequency-Dependent Squeezing for Advanced LIGO.

The first detection of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015 launched the era of gravitational-wave astronomy. The quest for gravitational-wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light, is being used to improve the shot-noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above ∼50 Hz. Below this frequency, quantum backaction, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30 Hz, using a 16-m-long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as "A+."

Quantum-Enhanced Advanced LIGO Detectors in the Era of Gravitational-Wave Astronomy.

The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).

Dynamics of transcriptome evolution in the model eukaryote Neurospora.

Mounting evidence indicates that changes in the transcriptome contribute significantly to the phenotypic differentiation of closely related species. Nonetheless, further genome-wide studies, spanning a broad range of organisms, are needed to decipher the factors driving transcriptome evolution. The model Neurospora (Ascomycota) comprises a simple system for empirically studying the evolutionary dynamics of the transcriptome. Here, we studied the evolution of gene expression in Neurospora crassa and Neurospora tetrasperma and show that patterns of transcriptome evolution are connected to genome evolution, tissue type and sexual identity (mating types, mat A and mat a) in these eukaryotes. Based on the comparisons of inter- and intraspecies expression divergence, our data reveal that rapid expression divergence is more apt to occur in sexual/female (SF) than vegetative/male (VM) tissues. In addition, interspecies gene expression and protein sequence divergence were strongly correlated for SF, but not VM, tissue. A correlation between transcriptome and protein evolution parallels findings from certain animals, but not yeast, and add support for the theory that expression evolution differs fundamentally among multicellular and unicellular eukaryotes. Finally, we found that sexual identity in these hermaphroditic Neurospora species is connected to interspecies expression divergence in a tissue-dependent manner: rapid divergence occurred for mat A- and mat a-biased genes from SF and VM tissues, respectively. Based on these findings, it is hypothesized that rapid interspecies transcriptome evolution is shifting the mating types of Neurospora towards distinct female and male phenotypes, that is, sexual dimorphism.

Genome-wide selection on codon usage at the population level in the fungal model organism Neurospora crassa.

Many organisms exhibit biased codon usage in their genome, including the fungal model organism Neurospora crassa. The preferential use of subset of synonymous codons (optimal codons) at the macroevolutionary level is believed to result from a history of selection to promote translational efficiency. At present, few data are available about selection on optimal codons at the microevolutionary scale, that is, at the population level. Herein, we conducted a large-scale assessment of codon mutations at biallelic sites, spanning more than 5,100 genes, in 2 distinct populations of N. crassa: the Caribbean and Louisiana populations. Based on analysis of the frequency spectra of synonymous codon mutations at biallelic sites, we found that derived (nonancestral) optimal codon mutations segregate at a higher frequency than derived nonoptimal codon mutations in each population; this is consistent with natural selection favoring optimal codons. We also report that optimal codon variants were less frequent in longer genes and that the fixation of optimal codons was reduced in rapidly evolving long genes/proteins, trends suggestive of genetic hitchhiking (Hill-Robertson) altering codon usage variation. Notably, nonsynonymous codon mutations segregated at a lower frequency than synonymous nonoptimal codon mutations (which impair translational efficiency) in each N. crassa population, suggesting that changes in protein composition are more detrimental to fitness than mutations altering translation. Overall, the present data demonstrate that selection, and partly genetic interference, shapes codon variation across the genome in N. crassa populations.

"Truffle sign". A suspicious malignant pattern of lymphadenopathies in children observed on ultrasound. Preliminary study.

BACKGROUND: The differential diagnosis of lymphadenopathies in children including benign and malignant conditions is often difficult to identify by ultrasound (US). The lymphadenopathies in children are frequent and mostly benign, therefore it is essential to decide what patients should undergo further studies. OBJECTIVE: To describe the potential usefulness of a new suspicious ultrasound sign on pediatric lymphadenopathies that can orient the diagnosis of malignancy. MATERIALS AND METHODS: We retrospectively reviewed all pediatric cases with lymphadenopathy suspicious of lymphoma or lymphoproliferative syndrome on soft tissue ultrasound from 2014 to 2021. Two expert ultrasound radiologists reviewed ultrasound images of these patients, associating the internal structure of infiltrated adenopathy with the internal structure of the truffles. RESULTS: On ultrasound, twelve cases presented enlarged lymphadenopathy with loss of internal structure, without hilum; mostly hypoechoic parenchyma, with some fine echogenic serpiginous linear surrounding hypoechoic pseudo nodular images, resembling the inner structure of black truffles. This US pattern looked suspicious and histological study was recommended. In 9 cases a lymphomatous infiltrated adenopathy was confirmed on biopsy. CONCLUSION: The truffle sign is a new potential suspicious ultrasound sign, that can suggest malignant lymphadenopathy in children. This ultrasound pattern can have some probable usefulness to the radiologist in order to recommend further studies, including histological study, that need to be validated by a larger sample. It is important to recognize easily and early the lymphomatous compromise in a lymph node.

Degeneration in codon usage within the region of suppressed recombination in the mating-type chromosomes of Neurospora tetrasperma.

The origin and early evolution of sex chromosomes are currently poorly understood. The Neurospora tetrasperma mating-type (mat) chromosomes have recently emerged as a model system for the study of early sex chromosome evolution, since they contain a young (<6 million years ago [Mya]), large (>6.6-Mb) region of suppressed recombination. Here we examined preferred-codon usage in 290 genes (121,831 codon positions) in order to test for early signs of genomic degeneration in N. tetrasperma mat chromosomes. We report several key findings about codon usage in the region of recombination suppression, including the following: (i) this region has been subjected to marked and largely independent degeneration among gene alleles; (ii) the level of degeneration is magnified over longer periods of recombination suppression; and (iii) both mat a and mat A chromosomes have been subjected to deterioration. The frequency of shifts from preferred codons to nonpreferred codons is greater for shorter genes than for longer genes, suggesting that short genes play an especially significant role in early sex chromosome evolution. Furthermore, we show that these degenerative changes in codon usage are best explained by altered selection efficiency in the recombinationally suppressed region. These findings demonstrate that the fungus N. tetrasperma provides an effective system for the study of degenerative genomic changes in young regions of recombination suppression in sex-regulating chromosomes.

Consequences of reproductive mode on genome evolution in fungi.

An organism's reproductive mode is believed to be a major factor driving its genome evolution. In theory, sexual inbreeding and asexuality are associated with lower effective recombination levels and smaller effective population sizes than sexual outbreeding, giving rise to reduced selection efficiency and genetic hitchhiking. This, in turn, is predicted to result in the accumulation of deleterious mutations and other genomic changes, for example the accumulation of repetitive elements. Empirical data from plants and animals supporting/refuting these theories are sparse and have yielded few conclusive results. A growing body of data from the fungal kingdom, wherein reproductive behavior varies extensively within and among taxonomic groups, has provided new insights into the role of mating systems (e.g., homothallism, heterothallism, pseudohomothallism) and asexuality, on genome evolution. Herein, we briefly review the theoretical relationships between reproductive mode and genome evolution and give examples of empirical data on the topic derived to date from plants and animals. We subsequently focus on the available data from fungi, which suggest that reproductive mode alters the rates and patterns of genome evolution in these organisms, e.g., protein evolution, mutation rate, codon usage, frequency of genome rearrangements and repetitive elements, and variation in chromosome size.

Evidence of the accumulation of allele-specific non-synonymous substitutions in the young region of recombination suppression within the mating-type chromosomes of Neurospora tetrasperma.

Currently, little is known about the origin and early evolution of sex chromosomes. This is largely due to the fact that ancient non-recombining sex chromosomes are highly degenerated, and thus provide little information about the early genomic events in their evolution. The Neurospora tetrasperma mating-type (mat) chromosomes contain a young (<6 Mya) and large region (>6.6 Mb) of suppressed recombination, thereby providing a model system to study early stages of sex chromosome evolution. Here, we examined alleles of 207 genes located on the N. tetrasperma mat a and mat A chromosomes to test for signs of genomic alterations at the protein level in the young region of recombination suppression. We report that the N. tetrasperma mat a and mat A chromosomes have each independently accumulated allele-specific non-synonymous codon substitutions in a time-dependent, and gene-specific manner in the recombinationally suppressed region. In addition, examination of the ratio (ω) of non-synonymous substitutions (dN) to synonymous substitutions (dS) using maximum likelihood analyses, indicates that such changes are associated with relaxed purifying selection, a finding consistent with genomic degeneration. We also reveal that sex specific biases in mutation rates or selection pressures are not necessary for genomic alterations in sex chromosomes, and that recombination suppression in itself is sufficient to explain these results. The present findings extend our current understanding of genomic events associated within the young region of recombination suppression in these fungal sex-regulating chromosomes.

Lessons from the battlefield: human factors in defence anaesthesia.

Anaesthetists in the Defence Medical Services spend most of their clinical time in the National Health Service and deploy on military operations every 6-18 months. The deployed operational environment has a number of key differences particularly as there is more severe trauma than an average UK hospital and injury patterns are mainly due to blast or ballistics. Equipment may also be unfamiliar and there is an expectation to be conversant with specific standard operating procedures. Anaesthetists must be ready to arrive and work in an established team and effective non-technical skills (or human factors) are important to ensure success. This article looks at some of the ways that the Department of Military Anaesthesia, Pain and Critical Care prepares Defence Anaesthetists to work in the deployed environment and focuses on the importance of human factors. This includes current work in the field hospital in Afghanistan and also preparing to work for the Royal Air Force and Royal Navy. We highlight the importance of human factors with reference to the type of case mix seen in the field hospital. We also detail the current pre-deployment training package, which employs multiple educational tools including high-fidelity simulation.

Simulation, human factors and defence anaesthesia.

Simulation in healthcare has come a long way since it's beginnings in the 1960s. Not only has the sophistication of simulator design increased, but the educational concepts of simulation have become much clearer. One particularly important area is that of non-technical skills (NTS) which has been developed from similar concepts in the aviation and nuclear industries. NTS models have been developed for anaesthetists and more recently for surgeons too. This has clear value for surgical team working and the recently developed Military Operational Surgical Training (MOST) course uses simulation and NTS to improve such team working. The scope for simulation in Defence medicine and anaesthesia does not stop here. Uses of simulation include pre-deployment training of hospital teams as well as Medical Emergency Response Team (MERT) and Critical Care Air Support Team (CCAST) staff. Future projects include developing Role 1 pre-deployment training. There is enormous scope for development in this important growth area of education and training.

Is G1 arrest in plant seeds induced by a p53-related pathway?

In mammals, p53 is crucial for inducing the genes that lead to G1 arrest following DNA damage, enabling DNA repair. However, the possibility that such a system exists in plants has attracted little attention. Even though some plant cDNA sequences with partial homology to p53 have been reported recently, there has been little analysis of how these molecules might relate to DNA damage. The lack of investigation into whether a DNA-damage-induced, p53-mediated G1-arrest pathway might exist in plants is remarkable given that plant DNA, like that of all organisms, is continually under the threat of attack.

Induction of tolerance to desiccation and cryopreservation in silver maple (Acer saccharinum) embryonic axes.

Twenty percent of of the world's flowering plants produce recalcitrant seeds (i.e., seeds that cannot withstand drying or freezing). We investigated whether the embryonic axis from the normally recalcitrant seeds of silver maple (Acer saccharinum L.) can be made tolerant to desiccation (10% water content) and low temperature (-196 degrees C, cryopreservation) by pretreatment with ABA or the compound tetcyclacis, which enhances endogenous ABA concentrations. Pretreatment of axes with both ABA and tetcyclacis increased germination after desiccation and freezing to 55% from a control value of zero. Pretreatment of axes with ABA and tetcyclacis increased the ABA content of the axes, as measured by enzyme-linked immunoassay, and stimulated the synthesis of storage and dehydrin-like proteins, believed to have a role in the desiccation tolerance of orthodox seeds.

A pilot study to assess the viability of a randomised controlled trial of methods of supplementary feeding of breast-fed pre-term babies.

OBJECTIVES: to compare the impact of two methods of supplementary feeding of pre-term babies (bottle vs cup) on subsequent breast feeding and to assess the feasibility of using a randomised controlled trial (RCT) to investigate the topic. DESIGN AND METHOD: small scale prospective RCT. Data on breast feeding, as defined as the exclusive method of feeding, were collected. A range of relevant bio-data was also collected and their impact on breast feeding assessed. SETTING: a special care baby unit in a District General Hospital in the UK. PARTICIPANTS: over a three-month period, all pre-term babies (32-37 weeks' gestation) who fulfilled the inclusion criteria and has been born to mothers who had expressed a pre-partum desire to breast feed, who had consented to take part, were included (n=14). PROCEDURE: the eligible babies were randomly allocated to supplementary feeding of breast milk, via either a cup or a bottle. Whether or not the baby was being breast fed at discharge was noted. FINDINGS: the study suggested that this RCT framework is a viable method of investigating baby feeding. Because of the small-scale nature of the project, the actual database must be treated with extreme caution. No significant differences were found between the two groups in terms of breast feeding. However, the mothers reported high levels of support and also the breast-feeding rates were above the national averages. These two findings could have contributed to the non-significant results observed in this analysis. CONCLUSIONS: if the present findings could be supported by further research, then the non-significant results relating method of supplementary feeds to subsequent breast feeding could be explained by reference to three factors. Firstly, there is, in fact, no real effect of method of supplementary feeding and subsequent breast feeding; secondly, the method adopted differed from existing research and thus may be expected to produce non-corroborative results; and finally, the overall levels of breast feeding within the Unit generally were higher than the national average. The relevance of the RCT for investigating this subject is also discussed with reference to the present data set. Further experimental work to develop these ideas and to identify causal links is required.

An analysis of professional, specialist and advanced nursing practice in critical care.

A recent document, The Future of Professional Practice--Standards for Education and Practice Following Registration (United Kingdom Central Council (UKCC) 1994a), has laid down a structure for clinical practice, providing a pathway for nurses to progress from the professional level, through to specialist and advanced levels, according to clinical expertise and educational preparation. The purpose of this article thus sets out to analyse critically these distinct levels in relation to critical care nursing. In particular, the paper discusses the development of advanced practice and how the proposed levels may be integrated within critical care.

Evolution of synonymous codon usage in Neurospora tetrasperma and Neurospora discreta.

Neurospora comprises a primary model system for the study of fungal genetics and biology. In spite of this, little is known about genome evolution in Neurospora. For example, the evolution of synonymous codon usage is largely unknown in this genus. In the present investigation, we conducted a comprehensive analysis of synonymous codon usage and its relationship to gene expression and gene length (GL) in Neurospora tetrasperma and Neurospora discreta. For our analysis, we examined codon usage among 2,079 genes per organism and assessed gene expression using large-scale expressed sequenced tag (EST) data sets (279,323 and 453,559 ESTs for N. tetrasperma and N. discreta, respectively). Data on relative synonymous codon usage revealed 24 codons (and two putative codons) that are more frequently used in genes with high than with low expression and thus were defined as optimal codons. Although codon-usage bias was highly correlated with gene expression, it was independent of selectively neutral base composition (introns); thus demonstrating that translational selection drives synonymous codon usage in these genomes. We also report that GL (coding sequences [CDS]) was inversely associated with optimal codon usage at each gene expression level, with highly expressed short genes having the greatest frequency of optimal codons. Optimal codon frequency was moderately higher in N. tetrasperma than in N. discreta, which might be due to variation in selective pressures and/or mating systems.

The influence of environmental factors, the pollen : ovule ratio and seed bank persistence on molecular evolutionary rates in plants.

One of the main goals of molecular evolutionary biology is to determine the factors that influence the evolutionary rate of selectively neutral DNA, but much remains unknown, especially for plants. Key factors that could alter the mutation rate include environmental tolerances (because they reflect a plants vulnerability to changes in habitat), the pollen:ovule ratio (as it is associated with the number of mitotic divisions) and seed longevity (because this influences the number of generations per unit time in plants). This is the first study to demonstrate that seed bank persistence and drought tolerance are positively associated with molecular evolutionary rates in plants and that pollen:ovule ratio, shade tolerance and salinity tolerance have no detectable relationship. The implications of the findings to our understanding of the impact of environmental agents, the number of cell divisions and cell aging on neutral DNA sequence evolution are discussed.

Moving forward in determining the causes of mutations: the features of plants that make them suitable for assessing the impact of environmental factors and cell age.

Currently, the types of factors that impact the mutation rate is a controversial issue. The marked attention towards identifying the factors that impact the genomic mutation rate is justified because mutations are the source of genetic variation underlying evolution and because many mutations have deleterious effects and can cause diseases. Although data showing correlations between germ cell division number and mutation rates (from epidemiological studies and molecular evolutionary rate analyses) have suggested that most mutations in animals are replication errors, this notion is highly debated and inconsistencies in the correlations suggest that other, replication-independent factors, could play an important role. Likely candidates include environmental parameters and cell age, but these issues have proved to be difficult to study using animals and in vitro systems, and consequently, very few or no data currently exist. The specific features of plants that make them powerful model systems for revealing the influence of the environment (natural environmental factors) and cell age on the spontaneous genomic mutation rate are discussed here. Overall, the evidence suggests that plants could be key biological systems for advancing our knowledge about how and why heritable mutations arise.