Patterns of Fetal Heart Rate Response at ∼30 Weeks Gestation Predict Size at Birth

There is evidence that fetal exposure to maternal stress is associated with adverse birth outcomes. Less is known about the association between fetal responses to a stressor and indicators of fetal maturity and developmental outcomes. The purpose of the present study was to determine whether fetal heart rate (FHR) patterns in response to a startling stimulus at ∼30 weeks of gestation were associated with gestational age at birth and birth weight. FHR was measured in 156 maternal–fetal dyads following a vibroacoustic stimulus. All pregnancies were singleton intrauterine pregnancies in English-speaking women who were primarily married, middle class, White and at least 18 years of age. Group-based trajectory modeling identified five groups of fetuses displaying distinctive longitudinal trajectories of FHR response to the startling stimulus. The FHR group trajectories were significantly associated with birth weight percentile (P \u3c 0.01) even after controlling for estimated fetal weight at the time of assessment and parity, which are the known factors influencing birth weight (P \u3c 0.01). Post hoc analyses indicated that two groups accounted for the association between FHR patterns and birth weight. The group (n = 23) with the lowest birth weight exhibited an immediate FHR deceleration followed by an immediate acceleration that does not recover. An FHR pattern characterized by immediate and fast acceleration to the peak and a slow discovery to baseline was associated with the highest birth weight. This is the first direct evidence showing that low birth weight and the resulting neurological consequences may have their origins in early fetal development

Development of temporal auditory processing in childhood: Changes in efficiency rather than temporal-modulation selectivity

The ability to detect amplitude modulation (AM) is essential to distinguish the spectro-temporal features of speech from those of a competing masker. Previous work shows that AM sensitivity improves until 10 years of age. This may relate to the development of sensory factors (tuning of AM filters, susceptibility to AM masking) or to changes in processing efficiency (reduction in internal noise, optimization of decision strategies). To disentangle these hypotheses, three groups of children (5–11 years) and one of young adults completed psychophysical tasks measuring thresholds for detecting sinusoidal AM (with a rate of 4, 8, or 32 Hz) applied to carriers whose inherent modulations exerted different amounts of AM masking. Results showed that between 5 and 11 years, AM detection thresholds improved and that susceptibility to AM masking slightly increased. However, the effects of AM rate and carrier were not associated with age, suggesting that sensory factors are mature by 5 years. Subsequent modelling indicated that reducing internal noise by a factor 10 accounted for the observed developmental trends. Finally, children’s consonant identification thresholds in noise related to some extent to AM sensitivity. Increased efficiency in AM detection may support better use of temporal information in speech during childhood

The weakness of diffuse bands in nebular environments. Possible impact on thePAH+ hypothesis

It has been widely suggested that PAH cations (PAH+) may be the carriers of the diffuse interstellar bands, so it is of interest to probe diffuse behavior in regions suspected of having high abundances of PAHs. Here we examine the strengths of several of the visible-wavelength diffuse interstellar bands in two nebular environments where infrared emission and ultraviolet indicators show that PAHs are abundant. One might expect the PAHs to be predominantly positively ionized in these regions, yet the diffuse bands are systematically weak. This led us to examine the ionization balance for see whether the weakness of the diffuse bands might rule out PAH cations as the carriers. We find that this conclusion is ambiguous, however, due to the very rapid rates for recombination of PAHs: under conditions that may reasonably represent our observed nebulae, the PAHs might be in predominantly neutral form. If so, this would explain the weakness of the diffuse bands, but leaves open some very perplexing questions about where the PAHs might be dominantly in cation form, hence where the diffuse bands do arise if they are due to PAH+

The weakness of diffuse bands in nebular environments. Possible impact on thePAH+ hypothesis

It has been widely suggested that PAH cations (PAH+) may be the carriers of the diffuse interstellar bands, so it is of interest to probe diffuse behavior in regions suspected of having high abundances of PAHs. Here we examine the strengths of several of the visible-wavelength diffuse interstellar bands in two nebular environments where infrared emission and ultraviolet indicators show that PAHs are abundant. One might expect the PAHs to be predominantly positively ionized in these regions, yet the diffuse bands are systematically weak. This led us to examine the ionization balance for see whether the weakness of the diffuse bands might rule out PAH cations as the carriers. We find that this conclusion is ambiguous, however, due to the very rapid rates for recombination of PAHs: under conditions that may reasonably represent our observed nebulae, the PAHs might be in predominantly neutral form. If so, this would explain the weakness of the diffuse bands, but leaves open some very perplexing questions about where the PAHs might be dominantly in cation form, hence where the diffuse bands do arise if they are due to PAH+

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Identification of regeneration-associated genes after central and peripheral nerve injury in the adult rat

Background: It is well known that neurons of the peripheral nervous system have the capacity to regenerate a severed axon leading to functional recovery, whereas neurons of the central nervous system do not regenerate successfully after injury. The underlying molecular programs initiated by axotomized peripheral and central nervous system neurons are not yet fully understood.Results: To gain insight into the molecular mechanisms underlying the process of regeneration in the nervous system, differential display polymerase chain reaction has been used to identify differentially expressed genes following axotomy of peripheral and central nerve fibers. For this purpose, axotomy induced changes of regenerating facial nucleus neurons, and non-regenerating red nucleus and Clarke's nucleus neurons have been analyzed in an intra-animal side-to-side comparison. One hundred and thirty five gene fragments have been isolated, of which 69 correspond to known genes encoding for a number of different functional classes of proteins such as transcription factors, signaling molecules, homeobox-genes, receptors and proteins involved in metabolism. Sixty gene fragments correspond to genomic mouse sequences without known function. In situ-hybridization has been used to confirm differential expression and to analyze the cellular localization of these gene fragments. Twenty one genes (similar to 15%) have been demonstrated to be differentially expressed.Conclusions: The detailed analysis of differentially expressed genes in different lesion paradigms provides new insights into the molecular mechanisms underlying the process of regeneration and may lead to the identification of genes which play key roles in functional repair of central nervous tissues

Maternal Cortisol Concentrations During Pregnancy and Sex-Specific Associations With Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors

Background: Maternal cortisol during pregnancy has the potential to influence rapidly developing fetal brain systems that are commonly altered in neurodevelopmental and psychiatric disorders. Research examining maternal cortisol concentrations across pregnancy and offspring neurodevelopment proximal to birth is needed to advance understanding in this area and lead to insight into the etiology of these disorders. Methods: Participants were 70 adult women recruited during early pregnancy and their infants born after 34 weeks gestation. Maternal cortisol concentrations were assessed serially over 4 days in early, mid, and late gestation. Resting state functional connectivity magnetic resonance imaging of the neonatal amygdala was examined. Mothers reported on children's internalizing behavior problems at 24 months of age. Results: Maternal cortisol concentrations during pregnancy were significantly associated with neonatal amygdala connectivity in a sex-specific manner. Elevated maternal cortisol was associated with stronger amygdala connectivity to brain regions involved in sensory processing and integration, as well as the default mode network in girls, and with weaker connectivity to these brain regions in boys. Elevated maternal cortisol was associated with higher internalizing symptoms in girls only, and this association was mediated by stronger neonatal amygdala connectivity. Conclusions: Normative variation in maternal cortisol during pregnancy is associated with the coordinated functioning of the amygdala soon after birth in a sex-specific manner. The identified pathway from maternal cortisol to higher internalizing symptoms in girls via alterations in neonatal amygdala connectivity may be relevant for the etiology of sex differences in internalizing psychiatric disorders, which are more prevalent in women

The meaning of life in a developing universe

The evolution of life on Earth has produced an organism that is beginning to model and understand its own evolution and the possible future evolution of life in the universe. These models and associated evidence show that evolution on Earth has a trajectory. The scale over which living processes are organized cooperatively has increased progressively, as has its evolvability. Recent theoretical advances raise the possibility that this trajectory is itself part of a wider developmental process. According to these theories, the developmental process has been shaped by a larger evolutionary process that involves the reproduction of universes. This evolutionary process has tuned the key parameters of the universe to increase the likelihood that life will emerge and develop to produce outcomes that are successful in the larger process (e.g. a key outcome may be to produce life and intelligence that intentionally reproduces the universe and tunes the parameters of ‘offspring’ universes). Theory suggests that when life emerges on a planet, it moves along this trajectory of its own accord. However, at a particular point evolution will continue to advance only if organisms emerge that decide to advance the evolutionary process intentionally. The organisms must be prepared to make this commitment even though the ultimate nature and destination of the process is uncertain, and may forever remain unknown. Organisms that complete this transition to intentional evolution will drive the further development of life and intelligence in the universe. Humanity’s increasing understanding of the evolution of life in the universe is rapidly bringing it to the threshold of this major evolutionary transition

On Tackling the Limits of Resolution in SAT Solving

The practical success of Boolean Satisfiability (SAT) solvers stems from the CDCL (Conflict-Driven Clause Learning) approach to SAT solving. However, from a propositional proof complexity perspective, CDCL is no more powerful than the resolution proof system, for which many hard examples exist. This paper proposes a new problem transformation, which enables reducing the decision problem for formulas in conjunctive normal form (CNF) to the problem of solving maximum satisfiability over Horn formulas. Given the new transformation, the paper proves a polynomial bound on the number of MaxSAT resolution steps for pigeonhole formulas. This result is in clear contrast with earlier results on the length of proofs of MaxSAT resolution for pigeonhole formulas. The paper also establishes the same polynomial bound in the case of modern core-guided MaxSAT solvers. Experimental results, obtained on CNF formulas known to be hard for CDCL SAT solvers, show that these can be efficiently solved with modern MaxSAT solvers

2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry

Objectives: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. Background: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. Methods: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. Results: During the current observation 37788 doses of Gadolinium based contrast agent were administered to 37788 patients. The mean dose was 24.7 ml (range 5–80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12 %). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05 % (linear non-ionic agent gadodiamide) to 0.42 % (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05 % (risk stratification in suspected CAD) to 0.22 % (viability in known CAD). Conclusions: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the “off-label” use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events