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A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
Perinatal maternal high-fat diet (HFD) increases susceptibility to obesity and fatty liver diseases in adult offspring, which can be attenuated by the potent hypolipidaemic action of fish oil (FO), an n-3 PUFA source, during adult life. Previously, we described that adolescent HFD offspring showed resistance to FO hypolipidaemic effects, although FO promoted hepatic molecular changes suggestive of reduced lipid accumulation. Here, we investigated whether this FO intervention only during the adolescence period could affect offspring metabolism in adulthood. Then, female Wistar rats received isoenergetic, standard (STD: 9 % fat) or high-fat (HFD: 28·6 % fat) diet before mating, and throughout pregnancy and lactation. After weaning, male offspring received the standard diet; and from 25 to 45 d old they received oral administration of soyabean oil or FO. At 150 d old, serum and hepatic metabolic parameters were evaluated. Maternal HFD adult offspring showed increased body weight, visceral adiposity, hyperleptinaemia and decreased hepatic pSTAT3/STAT3 ratio, suggestive of hepatic leptin resistance. FO intake only during the adolescence period reduced visceral adiposity and serum leptin, regardless of maternal diet. Maternal HFD promoted dyslipidaemia and hepatic TAG accumulation, which was correlated with reduced hepatic carnitine palmitoyl transferase-1a content, suggesting lipid oxidation impairment. FO intake did not change serum lipids; however, it restored hepatic TAG content and hepatic markers of lipid oxidation to STD offspring levels. Therefore, we concluded that FO intake exclusively during adolescence programmed STD offspring and reprogrammed HFD offspring male rats to a healthier metabolic phenotype in adult life, reducing visceral adiposity, serum leptin and hepatic TAG content in offspring adulthood.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
OBJECTIVES/SPECIFIC AIMS: The goal for this project is to determine the feasibility of using a novel multi-photon fiber-coupled microscope to aid surgeons in localizing STN during surgeries. In order to accomplish this goal, we needed to identify the source of a strong autofluorescent signal in the STN and determine whether we could use image classification methods to automatically distinguish STN from surrounding brain regions. METHODS/STUDY POPULATION: We acquired 3 cadaveric brains from the University of Colorado Anschutz Medical Campus, Department of Pathology. Two of these brains were non-PD controls whereas 1 was diagnosed with PD. We dissected a 10 square centimeter region of midbrain surrounding STN, then prepared this tissue for slicing on a vibratome or cryostat. Samples were immuno-labeled for various cellular markers for identification, or left unlabeled in order to observe the autofluorescence for image classification. RESULTS/ANTICIPATED RESULTS: The border of STN is clearly visible based on the density of a strong autofluorescent signal. The autofluorescent signal is visible using 2-photon (850–1040 nm excitation) and conventional confocal microscopy (488–647 nm excitation). We were also able to visualize blood vessels with second harmonic generation. The autofluorescent signal is quenched by high concentrations of Sudan-black B (0.5%–5%), and is primarily localized in microtubule-associated protein-2 (MAP2)+ cells, indicating that it is likely lipofuscin accumulation in neurons. Smaller lipofuscin particles also accumulate in microglia, identified based on ionized calcium binding adopter 1 (Iba1)+ labeling. We anticipate that colocalization analysis will confirm these qualitative observations. Using 2-photon images of the endogenous autofluorescent signal in these samples, we trained a logistic regression-based image classifier using features derived from gray-level co-occurrence matrices. Preliminary testing indicates that our classifier performed well, with a mean accuracy of 0.89 (standard deviation of 0.11) and a Cohen’s Kappa value of 0.76 (standard deviation of 0.24). We are currently using coherent anti-Stokes Raman scattering and third harmonic imaging to identify different features of myelin that can be used to distinguish between these regions and expect similar results. DISCUSSION/SIGNIFICANCE OF IMPACT: Traditional methods for localizing STN during DBS surgery include the use of stereotactic coordinates and multi-electrode recording (MER) during implantation. MERs are incredibly useful in DBS surgeries, but require penetration of brain structures in order to infer location. Using multi-photon microscopy techniques to aid identification of STN during DBS surgeries offers a number of advantages over traditional methods. For example, blood vessels can be clearly identified with second harmonic generation, something that is not possible with MER. Multi-photon microscopy also allows visualization deep into tissue without actually penetrating it. This ability to look within a depth of field is useful for detection of STN borders based on autofluorescent cell density. When combined with traditional stereotactic information, our preliminary image classification methods are a fast, reliable way to provide surgeons with extra information concerning their location in the midbrain. We anticipate that future advancements and refinements to our image classifier will only increase accuracy and the potential applications and value. In summary, these preliminary data support the feasibility of multi-photon microscopy to aid in the identification of target brain regions during DBS surgeries. The techniques described here complement and enhance current stereotactic and electrophysiological methods for DBS surgeries.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
The current study was aiming to report the prevalence of suboptimal vitamin D status among schoolchildren in Greece and investigate the role of sex, urbanisation and seasonality on vitamin D status. A sample of 2386 schoolchildren (9–13 years old) from four distinct prefectures was examined. The prevalence of 25-hydroxyvitamin D (25(OH)D) concentration <30 and <50 nmol/l (vitamin D deficiency and insufficiency respectively) was 5·2 and 52·5 %, respectively. Girls had a higher prevalence of 25(OH)D<30 (7·2 v. 3·2 %) and 50 nmol/l (57·0 v. 48·0 %) than boys (P<0·001). The highest prevalence rates of 25(OH)D<30 and 50 nmol/l (9·1 and 73·1 %, respectively) were observed during spring (April to June), whereas the lowest (1·5 and 31·9 %, respectively) during autumn (October to December). The prevalence of 25(OH)D<50 nmol/l was higher in urban/semi-urban than rural regions, particularly during spring months (74·6 v. 47·2 %; P<0·001). Female sex, urban/semi-urban region of residence and spring months were found to increase the likelihood of vitamin D deficiency and insufficiency, with the highest OR observed for spring months (7·47; 95 % CI 3·23, 17·3 and 5·14; 95 % CI 3·84, 6·89 for 25(OH)D<30 and 50 nmol/l respectively). In conclusion, despite the southerly latitude, the prevalence of low vitamin D status among primary schoolchildren in Greece is comparable to or exceeds the prevalence reported among children and adolescents on a European level. Sub-populations at highest risk are girls in urban/semi-urban areas during spring months, thus indicating the need for effective initiatives to support adequate vitamin D status in these population groups.
New radiocarbon calibration curves, IntCal04 and Marine04, have been constructed and internationally ratified to replace the terrestrial and marine components of IntCal98. The new calibration data sets extend an additional 2000 yr, from 0–26 cal kyr BP (Before Present, 0 cal BP = AD 1950), and provide much higher resolution, greater precision, and more detailed structure than IntCal98. For the Marine04 curve, dendrochronologically-dated tree-ring samples, converted with a box diffusion model to marine mixed-layer ages, cover the period from 0–10.5 cal kyr BP. Beyond 10.5 cal kyr BP, high-resolution marine data become available from foraminifera in varved sediments and U/Th-dated corals. The marine records are corrected with site-specific 14C reservoir age information to provide a single global marine mixed-layer calibration from 10.5–26.0 cal kyr BP. A substantial enhancement relative to IntCal98 is the introduction of a random walk model, which takes into account the uncertainty in both the calendar age and the 14C age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed here. The tree-ring data sets, sources of uncertainty, and regional offsets are presented in detail in a companion paper by Reimer et al. (this issue).
Accelerator mass spectrometry (AMS) measurement of 25 single-year tree rings from AD 1861–1885 at ca. ±3.5‰ precision shows no evidence of an anomalous 11-yr cycle of 14C near the Arctic Circle in the Mackenzie River area. However, the Δ14C measurements are lower on average by 2.7 ± 0.9 (ō)‰ relative to 14C measurements on tree rings from the Pacific Northwest (Stuiver and Braziunas 1993). We attribute this depression of Δ14C to thawing of the ice and snow cover followed by melting of frozen earth that releases trapped 14C-depleted CO2 to the atmosphere during the short growing season from May through August. Correlation of Δ14C with May–August estimated temperatures yields a correlation index of r = 0.60. The reduction in Δ14C is dominated by seven years of anomalous depletion. These years are 1861, 1867–1869, 1879–1880 and 1883. The years 1867–1869 are coincident with a very strong ENSO event.
Properties of the thermal radiation emitted by neutron stars (NSs) are determined by thin plasma layers (atmospheres) at their surfaces. The NS atmospheres are very different from those of usual stars due to the immense gravity and huge magnetic fields. Current models of hydrogen NS atmospheres show that the spectra deviate substantially from blackbody spectra of the same temperatures. Comparison of the model spectra with recent observations of soft X-ray and UV-optical radiation of NSs yields the surface temperatures considerably lower than those obtained from the blackbody fits. This conclusion have important implications for theories of NS cooling and for understanding fundamental properties of the superdense matter in the NS interiors.
Based on oral traditions, Rapa Nui is often portrayed as having a history of warfare and violence (Métraux, 1940; Routledge, 1919; Thomson, 1891) and a frequently cited hypothesis of societal collapse culminating in civil war (Diamond, 1995, 2005, 2007). There are, however, arguments against intertribal conflict resulting from such a decline (Hunt, 2007; Hunt and Lipo, 2009; Hunt and Lipo, 2011). While other types of data can be presented, direct evidence for both the presence and nature of past violence is marked on human skeletal remains. Previous analyses of injuries (Gill and Owsley, 1993; Owsley et al., 1994) determined that a relatively small percentage of Rapanui remains showed evidence of traumatic death. The current study revisits this topic among the prehistoric and historic Rapanui, using an expanded sample to assess physical evidence for injuries in the skull and limbs. The objective is to gain more definitive information about violence and warfare as factors related to the collapse of the society.
Easter Island warfare
Literature exploring and debating societal decline and collapse on Rapa Nui is extensive. Violence is a common theme in oral traditions recorded by late nineteenth- and early twentieth-century visitors. Among other legends in which conflict and cannibalism are prominent, a tribal war between the “Long Ears” and the “Short Ears” is described (Métraux, 1940; Routledge, 1919; Thomson, 1891). Multiple versions of this story exist, and while the details differ, the rivalry between the two groups results in the near-extermination of the Long Ears by the Short Ears. This event was dated to AD 1680 by Father Sebastián Englert (1948), based on his chronology of Rapa Nui and genealogical history (Lipo and Hunt, 2009). In 1956, the Norwegian Archaeological Expedition research team radiocarbon dated Poike Ditch, the location where most of the Long Ears were reportedly burned to death, to approximately AD 1676 (Smith, 1961a: 391). With reinforcement from this single radiocarbon date, AD 1680 became associated with a climactic event in Rapa Nui chronology that was used to delineate the Middle Period (ca. AD 1100–1680) from the Late Period (AD 1680–1868) (Lipo and Hunt, 2009; Smith, 1961a: 391, 1961b: 395).
The Deep Space Network (DSN) [operated by JPL under contract to the National Aeronautics and Space Administration] is implementing a Very Long Baseline Interferometry (VLBI) capability at DSS 63 (Spain), DSS 14 (California, USA), and DSS 43 (Australia) to support the navigation requirements of planetary space missions. The early development work for this system has already demonstrated the capability of measuring UT1 with a formal accuracy as low as 0.6 msec with only 6 hours of data. Further, a radio astrometric catalog of approximately 45 sources whose positions are known to better than has been constructed. In addition to these measurements, this paper describes the characteristics and anticipated performance of the complete VLBI system being implemented within the DSN for operational use in mid-1979. In particular, one of the capabilities of this system will be the measurement of UT1 and polar motion at weekly intervals. Although the navigation accuracy requirement is only 50 cm for the Voyager mission, this system should be capable of delivering UT1 and polar motion determinations with decimeter accuracy if it is operated at maximum performance. An additional requirement of this operational system is that it have the capability of providing these results within 24 hours of the actual observations.
Objectives: Health technology reassessment and disinvestment can be difficult due to uncertainties regarding available evidence. Pathology testing to investigate cobalamin (vitamin B12) deficiency is a strong case in point. We conducted a 3-month economic evaluation of five strategies for diagnosing and treating cobalamin deficiency in adult patients hypothetically presenting with new unexplained fatigue in the primary care setting. The first consultation per patient was considered. Screening tests other than serum cobalamin were not included.
Methods: A cost-effectiveness analysis was undertaken using a decision tree to represent the diagnostic / treatment pathways, with relevant cost and utility scores assigned to different stages in the evaluation process. Input parameter values were estimated from published evidence, supplemented by expert opinion, with sensitivity analysis undertaken to represent parameter uncertainty.
Results: Ordering serum vitamin B12 to assess cobalamin deficiency among patients with unexplained fatigue was not cost-effective in any patient population, irrespective of pretest prevalence of this deficiency. For patients with a pretest prevalence above 1 percent, treating all with oral vitamin B12 supplements without testing was most cost-effective, whereas watchful waiting with symptoms monitoring was most cost-effective for patients with lower pretest prevalence probabilities.
Conclusions: Substantial evidence gaps exist for parameter estimation: questionable cobalamin deficiency levels in the fatigued; debatable treatment methods; unknown natural history of the condition. Despite this, we reveal a robust path for disinvestment decision making in the face of a paradox between the evidence required to inform disinvestment compared with its paucity in informing initial funding decisions.
The present study examines the interaction between a polygenic score and an elementary school-based universal preventive intervention trial. The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation and tobacco use (Uhl et al., 2014). Using data from a longitudinal preventive intervention study, we examined age of first tobacco use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray. The polygenic score was computed using these data. Discrete-time survival analysis was employed to test for intervention main and interaction effects with the polygenic score. We found a main effect of the intervention, with the intervention participants reporting their first cigarette smoked at an age significantly later than controls. We also found an Intervention × Polygenic Score interaction, with participants at the higher end of the polygenic score benefitting the most from the intervention in terms of delayed age of first use. These results are consistent with Belsky and colleagues' (e.g., Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007; Belsky & Pleuss, 2009, 2013; Ellis, Boyce, Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2011) differential susceptibility hypothesis and the concept of “for better or worse,” wherein the expression of genetic variants are optimally realized in the context of an enriched environment, such as provided by a preventive intervention.