UNICORN Babies: Understanding Circulating and Cerebral Creatine Levels of the Preterm Infant. An Observational Study Protocol

Creatine is an essential metabolite for brain function, with a fundamental role in cellular (ATP) energy homeostasis. It is hypothesized that preterm infants will become creatine deplete in the early postnatal period, due to premature delivery from a maternal source of creatine and a limited supply of creatine in newborn nutrition. This potential alteration to brain metabolism may contribute to, or compound, poor neurological outcomes in this high-risk population. Understanding Creatine for Neurological Health in Babies (UNICORN) is an observational study of circulating and cerebral creatine levels in preterm infants. We will recruit preterm infants at gestational ages 23+0–26+6, 27+0–29+6, 30+0–32+6, 33+0–36+6, and a term reference group at 39+0–40+6 weeks of gestation, with 20 infants in each gestational age group. At birth, a maternal capillary blood sample, as well as a venous cord blood sample, will be collected. For preterm infants, serial infant plasma (heel prick), urine, and nutrition samples [total parenteral nutrition (TPN), breast milk, or formula] will be collected between birth and term “due date.” Key fetomaternal information, including demographics, smoking status, and maternal diet, will also be collected. At term corrected postnatal age (CPA), each infant will undergo an MRI/1H-MRS scan to evaluate brain structure and measure cerebral creatine content. A general movements assessment (GMA) will also be conducted. At 3 months of CPA, infants will undergo a second GMA as well as further neurodevelopmental evaluation using the Developmental Assessment of Young Children – Second Edition (DAYC-2) assessment tool. The primary outcome measures for this study are cerebral creatine content at CPA and plasma and urine creatine and guanidinoacetate (creatine precursor) concentrations in the early postnatal period. We will also determine associations between (1) creatine levels at term CPA and neurodevelopmental outcomes (MRI, GMA, and DAY-C); (2) dietary creatine intake and circulating and cerebral creatine content; and (3) creatine levels and maternal characteristics. Novel approaches are needed to try and improve preterm-associated brain injury. Inclusion of creatine in preterm nutrition may better support ex utero brain development through improved cerebral cellular energy availability during a period of significant brain growth and development.Ethics Ref: HDEC 18/CEN/7 New Zealand.ACTRN: ACTRN12618000871246

SN 2023ixf in Messier 101: Photo-ionization of Dense, Close-in Circumstellar Material in a Nearby Type II Supernova

We present UV/optical observations and models of supernova (SN) 2023ixf, a type II SN located in Messier 101 at 6.9 Mpc. Early-time ("flash") spectroscopy of SN 2023ixf, obtained primarily at Lick Observatory, reveals emission lines of H I, He I/II, C IV, and N III/IV/V with a narrow core and broad, symmetric wings arising from the photo-ionization of dense, close-in circumstellar material (CSM) located around the progenitor star prior to shock breakout. These electron-scattering broadened line profiles persist for $\sim$8 days with respect to first light, at which time Doppler broadened features from the fastest SN ejecta form, suggesting a reduction in CSM density at $r \gtrsim 10^{15}$ cm. The early-time light curve of SN2023ixf shows peak absolute magnitudes (e.g., $M_{u} = -18.6$ mag, $M_{g} = -18.4$ mag) that are $\gtrsim 2$ mag brighter than typical type II supernovae, this photometric boost also being consistent with the shock power supplied from CSM interaction. Comparison of SN 2023ixf to a grid of light curve and multi-epoch spectral models from the non-LTE radiative transfer code CMFGEN and the radiation-hydrodynamics code HERACLES suggests dense, solar-metallicity, CSM confined to $r = (0.5-1) \times 10^{15}$ cm and a progenitor mass-loss rate of $\dot{M} = 10^{-2}$ M$_{\odot}$yr$^{-1}$. For the assumed progenitor wind velocity of $v_w = 50$ km s$^{-1}$, this corresponds to enhanced mass-loss (i.e., ``super-wind'' phase) during the last $\sim$3-6 years before explosion.Comment: 18 pages, 8 figures. Submitted to ApJ

SN 2022oqm: A Multi-peaked Calcium-rich Transient from a White Dwarf Binary Progenitor System

We present the photometric and spectroscopic evolution of SN 2022oqm, a nearby multi-peaked hydrogen- and helium-weak calcium-rich transient (CaRT). SN 2022oqm was detected 19.9 kpc from its host galaxy, the face-on spiral galaxy NGC 5875. Extensive spectroscopic coverage reveals a hot (T >= 40,000 K) continuum and carbon features observed ~1 day after discovery, SN Ic-like photospheric-phase spectra, and strong forbidden calcium emission starting 38 days after discovery. SN 2022oqm has a relatively high peak luminosity (MB = -17 mag) for CaRTs, making it an outlier in the population. We determine that three power sources are necessary to explain SN 2022oqm's light curve, with each power source corresponding to a distinct peak in its light curve. The first peak of the light curve is powered by an expanding blackbody with a power law luminosity, consistent with shock cooling by circumstellar material. Subsequent peaks are powered by a double radioactive decay model, consistent with two separate sources of photons diffusing through an optically thick ejecta. From the optical light curve, we derive an ejecta mass and 56Ni mass of ~0.89 solar masses and ~0.09 solar masses, respectively. Detailed spectroscopic modeling reveals ejecta that is dominated by intermediate-mass elements, with signs that Fe-peak elements have been well-mixed. We discuss several physical origins for SN 2022oqm and favor a white dwarf progenitor model. The inferred ejecta mass points to a surprisingly massive white dwarf, challenging models of CaRT progenitors.Comment: 33 pages, 17 figures, 5 tables, Submitted to Ap

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

The seeds of divergence: the economy of French North America, 1688 to 1760

Generally, Canada has been ignored in the literature on the colonial origins of divergence with most of the attention going to the United States. Late nineteenth century estimates of income per capita show that Canada was relatively poorer than the United States and that within Canada, the French and Catholic population of Quebec was considerably poorer. Was this gap long standing? Some evidence has been advanced for earlier periods, but it is quite limited and not well-suited for comparison with other societies. This thesis aims to contribute both to Canadian economic history and to comparative work on inequality across nations during the early modern period. With the use of novel prices and wages from Quebec—which was then the largest settlement in Canada and under French rule—a price index, a series of real wages and a measurement of Gross Domestic Product (GDP) are constructed. They are used to shed light both on the course of economic development until the French were defeated by the British in 1760 and on standards of living in that colony relative to the mother country, France, as well as the American colonies. The work is divided into three components. The first component relates to the construction of a price index. The absence of such an index has been a thorn in the side of Canadian historians as it has limited the ability of historians to obtain real values of wages, output and living standards. This index shows that prices did not follow any trend and remained at a stable level. However, there were episodes of wide swings—mostly due to wars and the monetary experiment of playing card money. The creation of this index lays the foundation of the next component. The second component constructs a standardized real wage series in the form of welfare ratios (a consumption basket divided by nominal wage rate multiplied by length of work year) to compare Canada with France, England and Colonial America. Two measures are derived. The first relies on a “bare bones” definition of consumption with a large share of land-intensive goods. This measure indicates that Canada was poorer than England and Colonial America and not appreciably richer than France. However, this measure overestimates the relative position of Canada to the Old World because of the strong presence of land-intensive goods. A second measure is created using a “respectable” definition of consumption in which the basket includes a larger share of manufactured goods and capital-intensive goods. This second basket better reflects differences in living standards since the abundance of land in Canada (and Colonial America) made it easy to achieve bare subsistence, but the scarcity of capital and skilled labor made the consumption of luxuries and manufactured goods (clothing, lighting, imported goods) highly expensive. With this measure, the advantage of New France over France evaporates and turns slightly negative. In comparison with Britain and Colonial America, the gap widens appreciably. This element is the most important for future research. By showing a reversal because of a shift to a different type of basket, it shows that Old World and New World comparisons are very sensitive to how we measure the cost of living. Furthermore, there are no sustained improvements in living standards over the period regardless of the measure used. Gaps in living standards observed later in the nineteenth century existed as far back as the seventeenth century. In a wider American perspective that includes the Spanish colonies, Canada fares better. The third component computes a new series for Gross Domestic Product (GDP). This is to avoid problems associated with using real wages in the form of welfare ratios which assume a constant labor supply. This assumption is hard to defend in the case of Colonial Canada as there were many signs of increasing industriousness during the eighteenth and nineteenth centuries. The GDP series suggest no long-run trend in living standards (from 1688 to circa 1765). The long peace era of 1713 to 1740 was marked by modest economic growth which offset a steady decline that had started in 1688, but by 1760 (as a result of constant warfare) living standards had sunk below their 1688 levels. These developments are accompanied by observations that suggest that other indicators of living standard declined. The flat-lining of incomes is accompanied by substantial increases in the amount of time worked, rising mortality and rising infant mortality. In addition, comparisons of incomes with the American colonies confirm the results obtained with wages— Canada was considerably poorer. At the end, a long conclusion is provides an exploratory discussion of why Canada would have diverged early on. In structural terms, it is argued that the French colony was plagued by the problem of a small population which prohibited the existence of scale effects. In combination with the fact that it was dispersed throughout the territory, the small population of New France limited the scope for specialization and economies of scale. However, this problem was in part created, and in part aggravated, by institutional factors like seigneurial tenure. The colonial origins of French America’s divergence from the rest of North America are thus partly institutional

Passage performance and behaviour of wild and stocked cyprinid fish at a sloping weir with a Low Cost Baffle fishway

Weir construction has fragmented many rivers, resulting in the exclusion of some fish populations from suitable habitat. A cheap retrofit fishway for small, sloping weirs is the Low Cost Baffle (LCB) solution – A series of notched baffles perpendicular to flow on the downstream weir face, generating an angled passage route across the weir face. To test the degree to which LCBs can pass upstream-moving, lowland-river fish at steep weirs, LCBs were fitted onto a 1:3.3-sloping gauging-weir face, in an urban tributary of the River Thames, England. The study also compared the passage of wild and stocked fish (the latter are employed to facilitate population recovery in restored English rivers). Passive Integrated Transponder (PIT) antennas were positioned on the weir to record the upstream movement of PIT-tagged barbel (Barbus barbus; nstock = 120), chub (Squalius cephalus; nstock = 119; nwild = 194), dace (Leuciscus leuciscus; nwild = 50), and roach (Rutilus rutilus; nwild = 30). Over six months, more stocked fish attempted passage (58.9%) than wild (14.6%; χ21 = 26.7, p < 0.001), but there was no difference in successful passage of those that attempted (stock = 34.0%; wild = 40.0%; χ21 = 0.5, p = 0.49). Successful passage was achieved under a range of flow conditions. This study finds that LCBs have the potential to facilitate passage for cyprinid fishes at steep urban weirs that cannot readily be removed, but there is need for design improvements. This study also indicates that stocked and wild fish exhibited similar passage success, a finding with important management implications for achieving dispersal of stocked fish as a rehabilitation measure