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The Ross Sea record of the Miocene Climatic Optimum (MCO; ∼ 16.9–14.7 Ma) and the Middle Miocene Climate Transition (MMCT; ∼ 14.7–13.8 Ma) provides critical insights into Antarctic ocean–cryosphere interactions during a time of extreme warmth and subsequent cooling. Here we report on Lower to Middle Miocene foraminiferal assemblages from the International Ocean Discovery Program (IODP) Site U1521 on the outer shelf of the central Ross Sea to identify regional shifts in environmental and water mass conditions and trace continental shelf evolution. We identified seven benthic biofacies clusters, dominated by abundant Globocassidulina subglobosa (a proposed indicator of proto-Circumpolar Deep Water, pCDW), Uvigerina cf. U. fueguina (high productivity and enhanced bottom-water currents), Nonionella spp. (high productivity), or Melonis spp. (high productivity) using a Q-mode cluster analysis to develop preliminary regional paleoenvironmental interpretations. Four unique assemblages, including Globobulimina cf. G. auriculata (high productivity and low oxygen), are also identified. Unit IV (representing the early MCO event) is a short-lived (∼ 80 ka), progradational, clast-poor sandy diamictite, likely deposited during deglaciation; the upper part of Unit IV is transitional with overlying Unit III. Unit IV sediments contain the most persistently abundant and diverse foraminiferal assemblages recovered at U1521 because they are mud-rich and diatom-poor, despite very high sedimentation rates. The benthic assemblages shift between Globocassidulina and Uvigerina dominance, suggesting changes in the pCDW influence relative to productivity and/or current activity. We suggest the abundance of Uvigerina (a shelf-edge proxy) in Unit IV records the northward progradation of the Ross continental shelf at this location during the late Early to Middle Miocene. Unit III (MCO) was deposited in an open-marine setting, evident by the ice-rafted detritus or debris (IRD) clast-free, diatom-rich/diatom-bearing muds. The sporadic nature of foraminiferal abundances in Unit III is likely due to intervals of terrigenous mud alternating with more diatom-rich/diatom-bearing muds. As in Unit IV, the muddier lithologies (higher natural gamma ray (NGR) values) are more likely to preserve calcareous foraminifera, whereas the most diatom-rich sediments (lower NGR values) are more corrosive to carbonate. We interpret the muddier intervals as interglacials with incursions of pCDW, as indicated by increased Globocassidulina subglobosa, and sporadic occurrences of rare warmer-water planktic foraminifera. Collectively, these multiple incursions of warmer-water planktic foraminifera provide evidence for polar amplification in the Ross Sea during the MCO and MMCT. The diatom-rich muds are interpreted as glacials during the MCO with open-marine conditions and higher productivity. The dominance of Globobulimina in the upper part of Unit III corresponds with the carbon maximum of Carbon Maxima 2 (CM2) and low-oxygen conditions in the sediments at ∼ 16.1 Ma. Subsequent glaciation (including Mi2, Miocene Isotope event 2), marine-based ice sheet grounding, and erosion on the shallow shelf are recorded by the widespread Ross Sea Unconformity 4 (RSU4; ∼ 15.95–14.2 Ma) at Site U1521. Unit II (MMCT) likely represents sedimentation in the interval between the RSU4 and the Mi3 (Miocene Isotope event 3) glaciation at ∼ 13.9–13.8 Ma. The benthic biofacies composition of Unit II shows a further increase in neritic taxa, including Elphidium magellanicum and Epistominella vitrea, suggesting continued shoaling of the continental shelf, which facilitated the growth of marine-based ice sheets during the Middle Miocene. Our initial correlation between Site U1521 and the ANtarctic geological DRILLing Project (ANDRILL) site, AND-2A, yields similar environmental interpretations, including peak warm events 3 and 4 during the MCO, supported by the foraminifera and unit lithologies. Suspected glacial intervals during the MCO, including Mi2 at the top of Unit III, correlate well with the reconstructed deep-sea estimates of ice volume changes (seawater δ18Osw record) from the Ocean Drilling Program (ODP) Site 1171 on the South Tasman Rise.

ABSTRACT: The objective of this study was to quantify the effects of different milk flow-rate switch-point settings on milking duration, somatic cell count (SCC), strip milk, teat condition, and milk yield in a grass-based system in a long-term experiment. Much work has already been conducted providing strong support for significant reduction in milking duration without effects on yield through increasing the flow-rate switch-point at which vacuum to the milking cluster ceases and the cluster is removed from the cow by means of a retracting cord. However, in practice many farms have not adopted this labor-saving technology on the basis that it may increase milk SCC. Recent research on commercial Irish dairy herds identified the contagious mastitis-causing pathogen Staphylococcus. aureus as the most prevalent pathogen detected. Staph. aureus could have a cyclical shedding pattern which would inhibit detection at certain time points. Therefore, to reliably assess the effect of milk flow-rate switch-points on SCC, a long-term study was required, consisting of multiple observations on cow-level SCC. The present study filled this gap in knowledge by informing on any effect that ceasing milking at different flow rates may have on milking duration and SCC levels, particularly with regard to spring calving grass-based systems. Four treatments, consisting of milk flow-rate switch-points increasing from 0.2 kg/min to 0.8 kg/min in steps of 0.2 kg/min, were deployed for 31 wk to cows at the Teagasc Research Centre at Moorepark, Ireland. The effect of treatment on daily milking duration was significant. The milking duration for a milk flow-rate switch-point of 0.8 kg/min was 95 s (14%) shorter than for 0.2 kg/min. We did not find a significant effect of increasing the milk flow-rate switch-point from 0.2 to 0.8 kg/min on milk yield or SCC in this long-term study. We did find a significant effect of week of experiment on milk SCC, whereby the SCC of the cows on the experiment increased similarly among treatment groups as lactation progressed. A significant reduction in dead time (time from cluster attachment to reach a milk flow rate of 0.2 kg/min) was also noted as the milk flow-rate switch-point increased. On average, reductions in dead time contributed 12% to the overall reductions in milking duration. Similarly, reductions in low flow time (time from a flow rate of 0.2 kg/min to cluster detachment at the end of milking) contributed 26% to the overall reductions in milking duration. Reductions in dead time and low flow time played a greater role in reducing p.m. milking duration rather than a.m. milking duration due to the milking interval practiced on the research farm.

Abstract The number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially. Using ATAC-Seq, RNA-seq, ribo-profiling and proteomics we observed distinct molecular consequences of single tRNA deletions. We show that tRNA-Phe-1-1 is required for neuronal function and its loss is partially compensated by increased expression of other tRNAs but results in mistranslation. In contrast, the other tRNA-Phe isodecoder genes buffer the loss of each of the remaining six tRNA-Phe genes. In the tRNA-Phe gene family, the expression of at least six tRNA-Phe alleles is required for embryonic viability and tRNA-Phe-1-1 is most important for development and survival. Our results reveal that the multi-copy configuration of tRNA genes is required to buffer translation and viability in mammals.

ABSTRACT: Automatic cluster removers (ACR) operate by ceasing vacuum to the cluster and detaching the milking unit from the udder by means of a retracting cord once the milk flow has decreased to a predefined level (i.e., the milk flow rate switch-point). There is a large body of literature on this topic indicating that increasing the flow rate switch-point (e.g., from 0.2 kg/min to 0.8 kg/min at the udder level) is effective in reducing milking duration while having little effect on milk yield or milk somatic cell count (SCC). However, despite these findings many farms still use a switch-point of 0.2 kg/min because it is believed that emptying the udder completely at each milking is a prerequisite for good dairy cow management, especially in relation to maintaining a low milk SCC. However, there may be additional undocumented benefits in terms of cow comfort to increasing the milk flow rate switch-point, because the low milk flow period at the end of milking is a high-risk time for inducing teat-barrel congestion. The objective of this study was to quantify the effect of 4 milk flow rate switch-point settings on cow comfort, milking duration, and milk yield. In this study, we applied 4 treatments consisting of different milk flow rate switch-points to cows in a crossover design in a spring calving grass based dairy herd in Ireland. The treatments were (1) MFR0.2, where the cluster was removed at a milk flow rate of 0.2 kg/min; (2) MFR0.4, where the cluster was removed at 0.4 kg/min; (3) MFR0.6, where the cluster was removed at 0.6 kg/min, and (4) MFR0.8, where the cluster was removed at 0.8 kg/min. Milking parameters were recorded by the parlor software and leg movements (i.e., kicks or steps) during milking were recorded with an accelerometer. These data were used as a proxy for cow comfort during milking. The results of this study showed significant differences in cow comfort across treatments, as indicated by cow stepping during milking, for a.m. milkings, but these differences were not detected for p.m. milkings, possibly because a.m. milkings were longer than p.m. milkings due to a 16:8 h milking interval on the research farm. Differences tended to distinguish the 2 lower-flow switch-point settings with greater leg movement against the 2 higher-flow switch-point settings with less leg movement during milking. The effect of treatment (milk flow rate switch-point) on daily milking duration was significant. The milk duration for MFR0.8 was 89 s (14%) shorter than MFR0.2. There was no significant effect of treatment on SCC in this study.

ABSTRACT: This study documents the effect of mechanical prestimulation on the milking duration of pasture-based cows in late lactation to better harness increased capacity of automation in the milk harvesting process. Premilking stimulation, provided via manual or mechanical means, has been shown to promote the milk letdown reflex and assist in achieving quick, comfortable, and complete milk removal from the udder. The literature is lacking knowledge on the effect of mechanical premilking stimulation on milking duration, especially in late lactation and in pasture-based systems, and many pasture-based farms do not practice a full premilking routine because of a lack of labor availability. The current study addresses this gap in knowledge. In this study, we tested 2 treatments: (1) the No Stim treatment used normal farm milking settings with no premilking preparation and (2) the Stim treatment used 60 s of mechanical premilking stimulation, with a rate of 120 cycles per minute and a pulsator ratio of 30:70 on cluster attachment. Once the 60 s of stimulation had elapsed, normal milking settings resumed for the remainder of the milking. Sixty cows were enrolled in the study, which ran for 20 d. The effect of treatment on a.m. milking duration was significant, a.m. milking duration for Stim was 12 s shorter than that of No Stim. The effect of treatment on p.m. milk duration was not significant. Treatment had no effect on a.m./p.m. milk yields, average milk flowrates or peak milk flowrates. Significant differences emerged between treatments on a.m. and p.m. dead time (time from cluster attachment to reach a milk flowrate of 0.2 kg/min). The a.m. and p.m. dead times were 6 s shorter for Stim compared with No Stim. The time taken to achieve peak milk flowrate (time to peak) at morning milking was 7 s shorter for Stim compared with No Stim, and treatment yielded no significant effects on time to peak at p.m. milkings. Treatment also had no significant effect on log10 somatic cell count. Although the percentage of congested teat-ends and teat-barrels was numerically lower for Stim versus No Stim, no statistical differences were detected across these measures. Based on the results of the study, we found merit in applying 60 s of mechanical pre-stimulation at a.m. milking from a milking duration perspective. However, the strategy was not as successful for the p.m. milking. Analysis of the milk flowrate profiles recorded during the study suggest potential utility in employing different machine settings for various milkings based on anticipated yield and level of udder fill.

The software tools and user interfaces for the registration and exploration of tissue data for the human reference atlas are presented, providing evaluation metrics for data quality examination and guidance for data acquisition in support of reference atlas construction.

Abstract Background Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperglycaemia. Insulin is considered first-line pharmacotherapy but is associated with hypoglycaemia, excessive gestational weight gain (GWG) and an increased caesarean delivery rate. Metformin is safe in selected groups of women with GDM but is not first-line therapy in many guidelines due to a lack of long-term data on efficacy. The EMERGE trial will evaluate the effectiveness of early initiation of metformin in GDM. Methods EMERGE is a phase III, superiority, parallel, 1:1 randomised, double-blind, placebo-controlled trial comparing the effectiveness of metformin versus placebo initiated by 28 weeks (+6 days) plus usual care. Women aged 18–50 years will be recruited. Women with established diabetes, multiple pregnancies, known major congenital malformation or small for gestational age (

Abstract Background Healthy gut microbiota is important for prognosis in cow's milk allergy (CMA). The application of synbiotics (specific pre‐ and probiotics) in extensively hydrolyzed formulae (eHFs) is a relatively new concept. Aims To evaluate a synbiotic‐containing, whey‐based eHF (SeHF) with galacto‐oligosaccharides, fructo‐oligosaccharides, and bifidobacterium breve M‐16V in infants with CMA. Materials and Methods A 31‐day one‐arm pilot study in 29 infants with CMA (mean age 30.8 weeks [SD 11]) was undertaken, with outcomes including gastrointestinal tolerance, atopic dermatitis symptoms, dietary intake, growth, SeHF acceptability, caregiver quality of life, and hospital‐related healthcare use. Results Significant improvements (p

Histones, proteins that bind DNA, are toxic for pathogens outside cells but can also cause multi-organ damage as seen in sepsis. Here the authors develop small negatively charged molecules that can be used as histone antidotes, and show that they improve the phenotype in mouse models with histone-related pathologies.

Background: As more research is conducted in Liberia, there is a need for laboratory reference limits for common chemistry and haematology values based on a healthy population. Reference limits from the United States may not be applicable. Objective: The aim of this study was to present laboratory reference ranges from a Liberian population and compare them to United States ranges. Methods: Serum chemistry and haematology values from 2529 adults and 694 children and adolescents obtained from two studies conducted in Liberia between 2015 to 2017 were used to determine reference limits. After removing outliers, the reference limits defined by the 2.5th and 97.5th percentiles were determined by sex in three age groups (6–11, 12–17, and 18+ years). Results: The median (interquartile range) of adults was 29 (23, 37) years; 44% were female. The median (interquartile range) for children and adolescents was 12 (9, 15) years; 53% were female. Several reference ranges determined using Liberian participants differed from those in the US. For chemistries, a high percentage of both adults and children/adolescents had high serum chloride levels based on United States ranges. For haematology, a high percentage of Liberian participants had haemoglobin and related assays below the lower limit of United States ranges. Conclusion: Chemistry and haematology reference intervals determined for a Liberian population of healthy individuals should be considered for establishing eligibility criteria and monitoring of laboratory adverse events for clinical trials as well as for use in clinical settings in Liberia and perhaps for other countries in Western Africa.

We report on a 59-year-old female with symptomatic cholelithiasis on a background of morbid obesity who underwent an elective LC with an uncomplicated intraoperative course; however, she experienced a refractory hypotension within one hour postoperatively with an acute haemoglobin drop requiring fluid resuscitation and blood transfusion. A triphasic computed tomography scan revealed a large intrahepatic subcapsular haematoma (ISH) measuring 21 cm×3.1 cm×17 cm surrounding the lateral surface of the right hepatic lobe without active bleeding. She was managed conservatively with serial monitoring of haemoglobin and haematoma size. A follow-up ultrasound scan after eight weeks confirmed complete resolution of the haematoma. Giant ISH is a fairly rare, but life-threatening complication following LC which merits special attention. This case demonstrates the necessity of close postoperative monitoring of patients undergoing LC and considering the possibility of ISH, although being rare event, in those who experience a refractory postoperative hypotension. It also highlights the decisive role of diagnostic imaging in securing a timely and accurate diagnosis of post LC-ISH.

The purpose of this study was to examine the relation between people’s attraction to celebrities and their interpersonal trust and attachment style. Previous research suggests that individuals with different attachment styles are differentially attracted to celebrities. We predicted that securely attached participants who mistrust, rather than trust, others tend to have higher levels of benign celebrity attraction. We found only partial support for our hypothesis. Surprisingly, there were no significant differences between different attachment styles on either of the two measures of celebrity admiration. These findings contribute to the literature on trust and celebrity worship by providing new information about how different attachment styles may (or may not) affect the relationships that people have with their favorite celebrity.

The Southern Hemisphere westerly winds (SHWWs) play a major role in controlling wind-driven upwelling of Circumpolar Deep Water (CDW) and outgassing of CO2 in the Southern Ocean, on interannual to glacial–interglacial timescales. Despite their significance in the global carbon cycle, our understanding of millennial- and centennial-scale changes in the strength and latitudinal position of the westerlies during the Holocene (especially since 5000 yr BP) is limited by a scarcity of palaeoclimate records from comparable latitudes. Here, we reconstruct middle to late Holocene SHWW variability using a fjord sediment core collected from the subantarctic Auckland Islands (51° S, 166° E), located in the modern centre of the westerly wind belt. Changes in drainage basin response to variability in the strength of the SHWW at this latitude are interpreted from downcore variations in magnetic susceptibility (MS) and bulk organic δ13C and atomic C ∕ N, which monitor influxes of lithogenous and terrestrial vs. marine organic matter, respectively. The fjord water column response to SHWW variability is evaluated using benthic foraminifer δ18O and δ13C, both of which are influenced by the isotopic composition of shelf water masses entering the fjord. Using these data, we provide marine and terrestrial-based evidence for increased wind strength from ∼ 1600 to 900 yr BP at subantarctic latitudes that is broadly consistent with previous studies of climate-driven vegetation change at the Auckland Islands. Comparison with a SHWW reconstruction using similar proxies from Fiordland suggests a northward migration of the SHWW over New Zealand during the first half of the last millennium. Comparison with palaeoclimate and palaeoceanographic records from southern South America and West Antarctica indicates a late Holocene strengthening of the SHWW after ∼ 1600 yr BP that appears to be broadly symmetrical across the Pacific Basin. Contemporaneous increases in SHWW at localities on either side of the Pacific in the late Holocene are likely controlled atmospheric teleconnections between the low and high latitudes, and by variability in the Southern Annular Mode and El Niño–Southern Oscillation.

Although osteoporosis reduces overall bone mass causing bone fragility, recent studies report that the remaining bone tissue is significantly stiffer. Preliminary studies indicate that alterations in bone tissue mineral content might explain these changes, albeit that other studies report conflicting observations. The objective of this study is to quantify whether the distribution of bone tissue mineral is altered during oestrogen deficiency. Individual trabeculae were harvested from the proximal femur of 7 ovariectomised sheep (OVX), sacrificed 12 months post-surgery, and 5 age-matched controls. Mineral content (wt% Ca) was determined using a quantitative backscattered scanning electron microscopy imaging approach. Mineral heterogeneity within individual trabeculae was compared by calculating the full width at half maximum (FWHM) of mineral density distributions. Mean calcium content, the spatial distribution of mineral within trabeculae and the inter-trabecular variation between regions of proximal femora were also compared. Oestrogen deficiency increased mineral heterogeneity within individual trabeculae compared to healthy controls, as measured by FWHM (3.57 ± 0.68 vs. 3.17 ± 0.36 wt% Ca, p = 0.04). In particular mineral variability increased between superficial and deep regions of trabeculae of OVX animals (p = 0.04). Interestingly, mineralisation variability between greater and lesser trochanters (i.e. intertrochanteric fracture line) was increased in OVX compared to CON, as indicated by a greater % difference in the standard deviation of trabecular mineral content (77.11 ± 11.70 vs. 45.64 ± 23.70 %, p = 0.03). Such changes are undetectable by evaluating the mean mineral content of bone tissue, but may contribute to changes in bone mechanical strength following osteoporotic bone loss.

Supernormal (SN) stimuli are artificial products that activate reward pathways and approach behavior more so than naturally occurring stimuli for which these systems were intended. Many modern consumer products (e.g., snack foods, alcohol, and pornography) appear to incorporate SN features, leading to excessive consumption, in preference to naturally occurring alternatives. No measure currently exists for the self-report assessment of individual differences or changes in susceptibility to such stimuli. Therefore, an anticipatory pleasure scale was modified to include items that represented both SN and natural (N) classes of rewarding stimuli. Exploratory factor analysis yielded a two-factor solution, and as predicted, N and SN items reliably loaded on separate dimensions. Internal reliability for the two scales was high, ρ =.93 and ρ =.90, respectively. The two-dimensional measure was evaluated via regression using the N and SN scale means as predictors and self-reports of daily consumption of 21 products with SN features as outcomes. As expected, SN pleasure ratings were related to higher SN product consumption, while N pleasure ratings had either negative or neutral associations to consumption of these products. We conclude that the resulting two-dimensional measure is a potentially reliable and valid self-report measure of differential preference for SN stimuli. While further evaluation is needed (e.g., using experimental measures), the proposed scale may play a useful role in the study of both trait- and state-based variation in human susceptibility to SN stimuli.

We present simulations of different types of biped walking machines that are stabilized in the lateral direction by adding a gyro. The simulations show that, in principle, it is indeed possible to stabilise biped walking machines. Examples presented in this work include a three-dimensional version of the simplest walking model, which is based on earlier investigations, and an actuated biped robot. Here, the gyro is used as a reaction wheel. Finally, a rotor–brake combination is outlined that was used in an artistic biped robot at the Aichi World Exhibition.

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Impalement injuries of the oral cavity are common in children and the potential for serious complications including internal carotid artery thrombosis can be unnoticed. We present a patient who sustained a penetrating injury in which a “tin whistle” caused herniation of the parotid gland which was not detected on clinical examination. We discuss the challenging clinical examination, the role of investigations, and consequences of these injuries aiming at increasing awareness and optimizing patient management.

The integrity of male germ cell genome is critical for the correct progression of spermatogenesis, successful fertilization, and proper development of the offspring. Several DNA repair pathways exist in male germ cells. However, unlike somatic cells, key components of such pathways remain largely unidentified. Gametogenetin (GGN) is a testis-enriched protein that has been shown to bind to the DNA repair protein FANCL via yeast-two-hybrid assays. This finding and its testis-enriched expression pattern raise the possibility that GGN plays a role in DNA repair during spermatogenesis. Herein we demonstrated that the largest isoform GGN1 interacted with components of DNA repair machinery in the mouse testis. In addition to FANCL, GGN1 interacted with the critical component of the Fanconi Anemia (FA) pathway FANCD2 and a downstream component of the BRCA pathway, BRCC36. To define the physiological function of GGN, we generated a Ggn null mouse line. A complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos. Moreover, pachytene spermatocytes of the Ggn heterozygous knockout mice showed an increased incidence of unrepaired DNA double strand breaks (DSBs). Together, our results suggest that GGN plays a role in male meiotic DSB repair and is absolutely required for the survival of pre-implantation embryos.

The Tmem26 gene encodes a novel protein that we have previously shown to be regulated by hedgehog signalling in the mouse limb. We now report that Tmem26 expression is spatially and temporally restricted in other regions of the mouse embryo, most notably the facial primordia. In particular, Tmem26 expression in the mesenchyme of the maxillary and nasal prominences is coincident with fusion of the primary palate. In the secondary palate, Tmem26 is expressed in the palatal shelves during their growth and fusion but is downregulated once fusion is complete. Expression was also detected at the midline of the expanding mandible and at the tips of the eyelids as they migrate across the cornea. Given the spatio-temporally restricted expression of Tmem26, we sought to uncover a functional role in embryonic development through targeted gene inactivation in the mouse. However, ubiquitous inactivation of Tmem26 led to no overt phenotype in the resulting embryos or adult mice, suggesting that TMEM26 function is dispensable for embryonic survival.