A Systematic Review of Magnesium Sulfate for Perinatal Neuroprotection: What Have We Learnt From the Past Decade?

There is an important unmet need to improve long term outcomes of encephalopathy for preterm and term infants. Meta-analyses of large controlled trials suggest that maternal treatment with magnesium sulfate (MgSO4) is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth. However, to date, follow up to school age has found an apparent lack of long-term clinical benefit. Because of this inconsistency, it remains controversial whether MgSO4 offers sustained neuroprotection. We systematically reviewed preclinical and clinical studies reported from January 1 2010, to January 31 2020 to evaluate the most recent advances and knowledge gaps relating to the efficacy of MgSO4 for the treatment of perinatal brain injury. The outcomes of MgSO4 in preterm and term-equivalent animal models of perinatal encephalopathy were highly inconsistent between studies. None of the perinatal rodent studies that suggested benefit directly controlled body or brain temperature. The majority of the studies did not control for sex, study long term histological and functional outcomes or use pragmatic treatment regimens and many did not report controlling for potential study bias. Finally, most of the recent preterm or term human studies that tested the potential of MgSO4 for perinatal neuroprotection were relatively underpowered, but nevertheless, suggest that any improvements in neurodevelopment were at best modest or absent. On balance, these data suggest that further rigorous testing in translational preclinical models of perinatal encephalopathy is essential to ensure safety and best regimens for optimal preterm neuroprotection, and before further clinical trials of MgSO4 for perinatal encephalopathy at term are undertaken

An Update of Our Understanding of Fetal Heart Rate Patterns in Health and Disease.

UNDERSTANDING FETAL HEART RATE PATTERNS THAT MAY PREDICT ANTENATAL AND INTRAPARTUM NEURAL INJURY: Christopher A. Lear, Jenny A. Westgate, Austin Ugwumadu, Jan G. Nijhuis, Peter R. Stone, Antoniya Georgieva, Tomoaki Ikeda, Guido Wassink , Laura Bennet , Alistair J. Gunn Seminars in Pediatric Neurology Volume 28, December 2018, Pages 3-16 Electronic fetal heart rate (FHR) monitoring is widely used to assess fetal well-being throughout pregnancy and labor. Both antenatal and intrapartum FHR monitoring are associated with a high negative predictive value and a very poor positive predictive value. This in part reflects the physiological resilience of the healthy fetus and the remarkable effectiveness of fetal adaptations to even severe challenges. In this way, the majority of "abnormal" FHR patterns in fact reflect a fetus' appropriate adaptive responses to adverse in utero conditions. Understanding the physiology of these adaptations, how they are reflected in the FHR trace and in what conditions they can fail is therefore critical to appreciating both the potential uses and limitations of electronic FHR monitoring

All-Versus-Nothing Proof of Einstein-Podolsky-Rosen Steering

Einstein-Podolsky-Rosen steering is a form of quantum nonlocality intermediate between entanglement and Bell nonlocality. Although Schr\"odinger already mooted the idea in 1935, steering still defies a complete understanding. In analogy to "all-versus-nothing" proofs of Bell nonlocality, here we present a proof of steering without inequalities rendering the detection of correlations leading to a violation of steering inequalities unnecessary. We show that, given any two-qubit entangled state, the existence of certain projective measurement by Alice so that Bob's normalized conditional states can be regarded as two different pure states provides a criterion for Alice-to-Bob steerability. A steering inequality equivalent to the all-versus-nothing proof is also obtained. Our result clearly demonstrates that there exist many quantum states which do not violate any previously known steering inequality but are indeed steerable. Our method offers advantages over the existing methods for experimentally testing steerability, and sheds new light on the asymmetric steering problem.Comment: 7 pages, 2 figures. Accepted in Sci. Re

Consensus on a video analysis framework of descriptors and definitions by the Rugby Union Video Analysis Consensus group

Using an expert consensus-based approach, a rugby union Video Analysis Consensus (RUVAC) group was formed to develop a framework for video analysis research in rugby union. The aim of the framework is to improve the consistency of video analysis work in rugby union and help enhance the overall quality of future research in the sport. To reach consensus, a systematic review and Delphi method study design was used. After a systematic search of the literature, 17 articles were used to develop the final framework that described and defined key actions and events in rugby union (rugby). Thereafter, a group of researchers and practitioners with experience and expertise in rugby video analysis formed the RUVAC group. Each member of the group examined the framework of descriptors and definitions and rated their level of agreement on a 5-point agreement Likert scale (1: strongly disagree; 2: disagree; 3: neitheragree or disagree; 4: agree; 5: strongly agree). The mean rating of agreement on the five-point scale (1: strongly disagree; 5: strongly agree) was 4.6 (4.3–4.9), 4.6 (4.4–4.9), 4.7 (4.5–4.9), 4.8 (4.6–5.0) and 4.8 (4.6–5.0) for the tackle, ruck, scrum, line-out and maul, respectively. The RUVAC group recommends using this consensus as the starting framework when conducting rugby video analysis research. Which variables to use (if not all) depends on the objectives of the study. Furthermore, the intention of this consensus is to help integrate video data with other data (eg, injury surveillance)

Therapeutic hypothermia translates from ancient history in to practice

Acute postasphyxial encephalopathy around the time of birth remains a major cause of death and disability. The possibility that hypothermia may be able to prevent or lessen asphyxial brain injury is a “dream revisited”. In this review, a historical perspective is provided from the first reported use of therapeutic hypothermia for brain injuries in antiquity, to the present day. The first uncontrolled trials of cooling for resuscitation were reported more than 50 y ago. The seminal insight that led to the modern revival of studies of neuroprotection was that after profound asphyxia, many brain cells show initial recovery from the insult during a short “latent” phase, typically lasting ~6 h, only to die hours to days later during a “secondary” deterioration phase characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Studies designed around this conceptual framework showed that mild hypothermia initiated as early as possible before the onset of secondary deterioration, and continued for a sufficient duration to allow the secondary deterioration to resolve, is associated with potent, long-lasting neuroprotection. There is now compelling evidence from randomized controlled trials that mild induced hypothermia significantly improves intact survival and neurodevelopmental outcomes to midchildhood

Quantitative Metabolomics by 1H-NMR and LC-MS/MS Confirms Altered Metabolic Pathways in Diabetes

Insulin is as a major postprandial hormone with profound effects on carbohydrate, fat, and protein metabolism. In the absence of exogenous insulin, patients with type 1 diabetes exhibit a variety of metabolic abnormalities including hyperglycemia, glycosurea, accelerated ketogenesis, and muscle wasting due to increased proteolysis. We analyzed plasma from type 1 diabetic (T1D) humans during insulin treatment (I+) and acute insulin deprivation (I-) and non-diabetic participants (ND) by 1H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. The aim was to determine if this combination of analytical methods could provide information on metabolic pathways known to be altered by insulin deficiency. Multivariate statistics differentiated proton spectra from I- and I+ based on several derived plasma metabolites that were elevated during insulin deprivation (lactate, acetate, allantoin, ketones). Mass spectrometry revealed significant perturbations in levels of plasma amino acids and amino acid metabolites during insulin deprivation. Further analysis of metabolite levels measured by the two analytical techniques indicates several known metabolic pathways that are perturbed in T1D (I-) (protein synthesis and breakdown, gluconeogenesis, ketogenesis, amino acid oxidation, mitochondrial bioenergetics, and oxidative stress). This work demonstrates the promise of combining multiple analytical methods with advanced statistical methods in quantitative metabolomics research, which we have applied to the clinical situation of acute insulin deprivation in T1D to reflect the numerous metabolic pathways known to be affected by insulin deficiency

Testing foundations of quantum mechanics with photons

The foundational ideas of quantum mechanics continue to give rise to counterintuitive theories and physical effects that are in conflict with a classical description of Nature. Experiments with light at the single photon level have historically been at the forefront of tests of fundamental quantum theory and new developments in photonics engineering continue to enable new experiments. Here we review recent photonic experiments to test two foundational themes in quantum mechanics: wave-particle duality, central to recent complementarity and delayed-choice experiments; and Bell nonlocality where recent theoretical and technological advances have allowed all controversial loopholes to be separately addressed in different photonics experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review articl

Characterization and Generation of Male Courtship Song in Cotesia congregata (Hymenoptera: Braconidae)

Background Male parasitic wasps attract females with a courtship song produced by rapid wing fanning. Songs have been described for several parasitic wasp species; however, beyond association with wing fanning, the mechanism of sound generation has not been examined. We characterized the male courtship song of Cotesia congregata (Hymenoptera: Braconidae) and investigated the biomechanics of sound production. Methods and Principal Findings Courtship songs were recorded using high-speed videography (2,000 fps) and audio recordings. The song consists of a long duration amplitude-modulated “buzz” followed by a series of pulsatile higher amplitude “boings,” each decaying into a terminal buzz followed by a short inter-boing pause while wings are stationary. Boings have higher amplitude and lower frequency than buzz components. The lower frequency of the boing sound is due to greater wing displacement. The power spectrum is a harmonic series dominated by wing repetition rate ~220 Hz, but the sound waveform indicates a higher frequency resonance ~5 kHz. Sound is not generated by the wings contacting each other, the substrate, or the abdomen. The abdomen is elevated during the first several wing cycles of the boing, but its position is unrelated to sound amplitude. Unlike most sounds generated by volume velocity, the boing is generated at the termination of the wing down stroke when displacement is maximal and wing velocity is zero. Calculation indicates a low Reynolds number of ~1000. Conclusions and Significance Acoustic pressure is proportional to velocity for typical sound sources. Our finding that the boing sound was generated at maximal wing displacement coincident with cessation of wing motion indicates that it is caused by acceleration of the wing tips, consistent with a dipole source. The low Reynolds number requires a high wing flap rate for flight and predisposes wings of small insects for sound production

Evolutionary relationships and divergence times among the native rats of Australia

Background The genus Rattus is highly speciose and has a complex taxonomy that is not fully resolved. As shown previously there are two major groups within the genus, an Asian and an Australo-Papuan group. This study focuses on the Australo-Papuan group and particularly on the Australian rats. There are uncertainties regarding the number of species within the group and the relationships among them. We analysed 16 mitochondrial genomes, including seven novel genomes from six species, to help elucidate the evolutionary history of the Australian rats. We also demonstrate, from a larger dataset, the usefulness of short regions of the mitochondrial genome in identifying these rats at the species level. Results Analyses of 16 mitochondrial genomes representing species sampled from Australo-Papuan and Asian clades of Rattus indicate divergence of these two groups ~2.7 million years ago (Mya). Subsequent diversification of at least 4 lineages within the Australo-Papuan clade was rapid and occurred over the period from ~ 0.9-1.7 Mya, a finding that explains the difficulty in resolving some relationships within this clade. Phylogenetic analyses of our 126 taxon, but shorter sequence (1952 nucleotides long), Rattus database generally give well supported species clades. Conclusions Our whole mitochondrial genome analyses are concordant with a taxonomic division that places the native Australian rats into the Rattus fuscipes species group. We suggest the following order of divergence of the Australian species. R. fuscipes is the oldest lineage among the Australian rats and is not part of a New Guinean radiation. R. lutreolus is also within this Australian clade and shallower than R. tunneyi while the R. sordidus group is the shallowest lineage in the clade. The divergences within the R. sordidus and R. leucopus lineages occurring about half a million years ago support the hypotheses of more recent interchanges of rats between Australia and New Guinea. While problematic for inference of deeper divergences, we report that the analysis of shorter mitochondrial sequences is very useful for species identification in rats

Apolipoprotein E Genotype and Cardiovascular Diseases in the Elderly

The apolipoprotein E (APOE) genotype is a genetic risk factor for dementia, Alzheimer’s disease, and cardiovascular disease (CVD). It includes three alleles (e2, e3, e4) that are located on chromosome 19q3.2. The e3 allele is the most common and is more common in people of Northern European ancestry and less common in those of Asian ancestry. Those with at least one e4 allele are at increased risk for CVD outcomes. It is well established that the presence of an e4 allele is linked to higher low-density lipoprotein cholesterol levels, even at young ages. Even though most CVD occurs in older people, there are few studies of the effects of APOE on CVD in older people. This review addresses recent research on the links between APOE, CVD, and vascular mechanisms by which APOE may affect CVD in the elderly