Non-destructive shadowgraph imaging of ultracold atoms

An imaging system is presented that is capable of far-detuned non-destructive imaging of a Bose-Einstein condensate with the signal proportional to the second spatial derivative of the density. Whilst demonstrated with application to $^{85}\text{Rb}$, the technique generalizes to other atomic species and is shown to be capable of a signal to noise of ${\sim}25$ at $1$GHz detuning with $100$ in-trap images showing no observable heating or atom loss. The technique is also applied to the observation of individual trajectories of stochastic dynamics inaccessible to single shot imaging. Coupled with a fast optical phase lock loop, the system is capable of dynamically switching to resonant absorption imaging during the experiment.Comment: 4 pages, 5 figure

Locally recurrent chondrosarcoma of the pelvis and limbs can only be controlled by wide local excision

Aims The purpose of this study was to investigate the potential for achieving local and systemic control after local recurrence of a chondrosarcoma of bone. Patients and Methods A total of 126 patients with local recurrence (LR) of chondrosarcoma (CS) of the pelvis or a limb bone were identified from a prospectively maintained database, between 1990 and 2015 at the Royal Orthopaedic Hospital, Birmingham, United Kingdom. There were 44 female patients (35%) and 82 male patients (65%) with a mean age at the time of LR of 56 years (13 to 96). The 126 patients represented 24.3% of the total number of patients with a primary CS (519) who had been treated during this period. Clinical data collected at the time of primary tumour and LR included the site (appendicular, extremity, or pelvis); primary and LR tumour size (in centimetres); type of operation at the time of primary or LR (limb-salvage or amputation); surgical margin achieved at resection of the primary tumour and the LR; grade of the primary tumour and the LR; gender; age; and oncological outcomes, including local recurrence-free survival and disease-specific survival. A minimum two years' follow-up and complete histopathology records were available for all patients included in the study. Results For patients without metastases prior to or at the time of local recurrence, the disease-specific survival after local recurrence was 62.5% and 45.5% at one and five years, respectively, After univariable analysis, significant factors predicting disease-specific survival were grade (p <0.001) and surgical margin (p = 0.044). After multivariable analysis, grade, increasing age at the time of diagnosis of local recurrence, and a greater time interval from primary surgery to local recurrence were significant factors for disease-specific survival. A secondary local recurrence was seen in 26% of patients. Wide margins were a good predictor of local recurrence-free survival for subsequent recurrences after univariable analysis when compared with intralesional margins (p = 0.002) but marginal margins did not reach statistical significance when compared with intralesional margins (p = 0.084). Conclusion In cases of local recurrence of a chondrosarcoma of bone, we have shown that if the tumour is non-metastatic at re-staging, an increase in disease-specific survival and in local recurrence-free survival is achievable, but only by resection of the local recurrence with a wide margin.Peer reviewe

Extreme value and cluster analysis of European daily temperature series

Time series of daily mean temperature obtained from the European Climate Assessment data set is analyzed with respect to their extremal properties. A time-series clustering approach which combines Bayesian methodology, extreme value theory and classification techniques is adopted for the analysis of the regional variability of temperature extremes. The daily mean temperature records are clustered on the basis of their corresponding predictive distributions for 25-, 50- and 100-year return values. The results of the cluster analysis showa clear distinction between the highest altitude stations, for which the return values are lowest, and the remaining stations. Furthermore, a clear distinction is also found between the northernmost stations in Scandinavia and the stations in central and southern Europe. This spatial structure of the return period distributions for 25-, 50- and 100-years seems to be consistent with projected changes in the variability of temperature extremes over Europe pointing to a different behavior in central Europe than in northern Europe and the Mediterranean area, possibly related to the effect of soil moisture and land-atmosphere coupling.‘Acções Integradas Luso-Espanholas’ under the grants E-83/09 and HP2008- 008

Maximizing Science Return from Future Rodent Experiments on the International Space Station (ISS): Tissue Preservation

To better understand how mammals adapt to long duration habitation in space, a system for performing rodent experiments on the ISS is under development; Rodent Research-1 is the first flight and will include validation of both on-orbit animal support and tissue preservation. To evaluate plans for on-orbit sample dissection and preservation, we simulated conditions for euthanasia, tissue dissection, and prolonged sample storage on the ISS, and we also developed methods for post-flight dissection and recovery of high quality RNA from multiple tissues following prolonged storage in situ for future science. Mouse livers and spleens were harvested under conditions that simulated nominal, on-orbit euthanasia and dissection operations including storage at -80 C for 4 months. The RNA recovered was of high quality (RNA Integrity Number, RIN(is) greater than 8) and quantity, and the liver enzyme contents and activities (catalase, glutathione reductase, GAPDH) were similar to positive controls, which were collected under standard laboratory conditions. We also assessed the impact of possible delayed on-orbit dissection scenarios (off-nominal) by dissecting and preserving the spleen (RNAlater) and liver (fast-freezing) at various time points post-euthanasia (from 5 min up to 105 min). The RNA recovered was of high quality (spleen, RIN (is) greater than 8; liver, RIN (is) greater than 6) and liver enzyme activities were similar to positive controls at all time points, although an apparent decline in select enzyme activities was evident at the latest time (105 min). Additionally, various tissues were harvested from either intact or partially dissected, frozen carcasses after storage for approximately 2 months; most of the tissues (brain, heart, kidney, eye, adrenal glands and muscle) were of acceptable RNA quality for science return, whereas some tissues (small intestine, bone marrow and bones) were not. These data demonstrate: 1) The protocols developed for future flight experiments will support science return despite delayed preservation post-euthanasia or prolonged storage, and 2) Many additional tissues for gene expression analysis can be obtained by dissection following prolonged storage of the tissue in situ at -80 C. These findings have relevance both to high value, ground-based experiments when sample collection capability is severely constrained, and to all future spaceflight experiments that entail on-orbit sample recovery by the ISS crew

Rodent Research Development for Long Duration Studies on the International Space Station

Rodent research in space is needed to advance our understanding of the health risks,consequences and possible countermeasures to protect crew during future, long duration missions. TheAnimal Enclosure Module (AEM) was designed originally to support habitation of rats and mice onrelatively short duration, Shuttle missions (<19 days). The AEM was flown previously on 27 SpaceShuttle missions, and recently was modified extensively to support future long duration space biology andbiomedical research on the International Space Station (ISS). In consultation with a Science WorkingGroup comprised of veterinarians and investigators experienced in rodent spaceflight experimentation inspace, the Rodent Habitat project team at Ames Research Center modified existing hardware, developednew hardware, operations, and science activities, and performed a series of ground-based operational andscience habitat verification tests in preparation for the first validation flight

Advances in Rodent Research Missions on the International Space Station

A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASAs Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASAs GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLabs open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the programs capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISSs capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Councils Decadal Survey released in 2011 and to maximize science return from each mission

Late Holocene palynology and palaeovegetation of tephra-bearing mires at Papamoa and Waihi Beach, western Bay of Plenty, North Island, New Zealand.

The vegetation history of two mires associated with Holocene dunes near the western Bay of Plenty coast, North Island, New Zealand, is deduced from pollen analysis of two cores. Correlation of airfall tephra layers in the peats, and radiocarbon dates, indicate that the mires at Papamoa and Waihi Beach are c. 4600 and c. 2900 conventional radiocarbon years old, respectively. Tephras used to constrain the chronology of the pollen record include Rotomahana (1886 AD), Kaharoa (700 yr B.P.), Taupo (Unit Y; 1850 yr B.P.), Whakaipo (Unit V; 2700 yr B.P.), Stent (Unit Q; 4000 yr B.P.), Hinemaiaia (Unit K; 4600 yr B.P.), and reworked Whakatane (c. 4800 yr B.P.) at Papamoa, and Kaharoa and Taupo at Waihi Beach. Peat accumulation rates at Papamoa from 4600 - 1850 yr B.P. range from 0.94 to 2.64 mm/yr (mean 1.37 mm/yr). At Waihi Beach, from 2900 yr B.P. - present day, they range from 0.11 to 0.21 mm/yr (mean 0.20 mm/yr). Peat accumulation at both sites was slowest from 1850 to 700 yr B.P., suggesting a drier overall climate during this interval. At both sites, the earliest organic sediments, which are underlain by marine or estuarine sands, yield pollen spectra indicating salt marsh or estuarine environments. Coastal vegetation communities declined at both sites, as sea level gradually fell or the coast prograded, and were eventually superseded by a low moor bog at Papamoa, and a mesotrophic swamp forest at Waihi Beach. These differences, and the marked variation in peat accumulation rates, probably reflect local hydrology and are unlikely to have been climatically controlled. The main regional vegetation during this period was mixed northern conifer-angiosperm forest. Kauri (Agathis australis) formed a minor component of these forests, but populations of this tree have apparently not expanded during the late Holocene at these sites, which are near its present southern limit. Occasional shortlived forest disturbances are detectable in these records, in particular immediately following the deposition of Taupo Tephra. However, evidence for forest clearance during the human era is blurred by the downward dislocation of modern adventi ve pollen at these sites, preventing the clear differentiation of the Polynesian and European eras

Evolution of 21st Century Sea Level Rise Projections

The modern era of scientific global‐mean sea level rise (SLR) projections began in the early 1980s. In subsequent decades, understanding of driving processes has improved, and new methodologies have been developed. Nonetheless, despite more than 70 studies, future SLR remains deeply uncertain. To facilitate understanding of the historical development of SLR projections and contextualize current projections, we have compiled a comprehensive database of 21st century global SLR projections. Although central estimates of 21st century global‐mean SLR have been relatively consistent, the range of projected SLR has varied greatly over time. Among studies providing multiple estimates, the range of upper projections shrank from 1.3–1.8 m during the 1980s to 0.6–0.9 m in 2007, before expanding again to 0.5–2.5 m since 2013. Upper projections of SLR from individual studies are generally higher than upper projections from the Intergovernmental Panel on Climate Change, potentially due to differing percentile bounds or a predisposition of consensus‐based approaches toward relatively conservative outcomes.Plain Language SummaryIn spite of more than 35 years of research, and over 70 individual studies, the upper bound of future global‐mean sea level rise (SLR) remains deeply uncertain. In an effort to improve understanding of the history of the science behind projected SLR, we present and analyze the first comprehensive database of 21st century global‐mean SLR projections. Results show a reduction in the range of SLR projections from the first studies through the mid‐2000s that has since reversed. In addition, results from this work indicate a tendency for Intergovernmental Panel on Climate Change reports to err on the side of least drama—a conservative bias that could potentially impede risk management.Key PointsWe present the first comprehensive database of 21st century global sea level rise projectionsUpper estimates of sea level rise in 2100 are often higher than upper bounds found in Intergovernmental Panel on Climate Change reportsA comparison of recent global sea level rise projections reveals far greater agreement among studies in 2050 compared to 2100Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147167/1/eft2484_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147167/2/eft2484.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147167/3/eft2_84-sup-0001-2018EF000991-Figs01.pd

Results of an open label feasibility study of sodium valproate in people with McArdle disease

McArdle disease results from a lack of muscle glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy. Animal model studies indicate that sodium valproate (VPA) can increase expression of phosphorylase in skeletal muscle affected with McArdle disease. This study was designed to assess whether VPA can modify expression of brain phosphorylase isoenzyme in people with McArdle disease. This phase II, open label, feasibility pilot study to assess efficacy of six months treatment with VPA (20 mg/kg/day) included 16 people with McArdle disease. Primary outcome assessed changes in VO2peak during an incremental cycle test. Secondary outcomes included: phosphorylase enzyme expression in post-treatment muscle biopsy, total distance walked in 12 min, plasma lactate change (forearm exercise test) and quality of life (SF36). Safety parameters. 14 participants completed the trial, VPA treatment was well tolerated; weight gain was the most frequently reported drug-related adverse event. There was no clinically meaningful change in any of the primary or secondary outcome measures including: VO2peak, 12 min walk test and muscle biopsy to look for a change in the number of phosphorylase positive fibres between baseline and 6 months of treatment. Although this was a small open label feasibility study, it suggests that a larger randomised controlled study of VPA, may not be worthwhile