Deterministic delivery of externally cold and precisely positioned single molecular ions

We present the preparation and deterministic delivery of a selectable number of externally cold molecular ions. A laser cooled ensemble of Mg^+ ions subsequently confined in several linear Paul traps inter-connected via a quadrupole guide serves as a cold bath for a single or up to a few hundred molecular ions. Sympathetic cooling embeds the molecular ions in the crystalline structure. MgH^+ ions, that serve as a model system for a large variety of other possible molecular ions, are cooled down close to the Doppler limit and are positioned with an accuracy of one micrometer. After the production process, severely compromising the vacuum conditions, the molecular ion is efficiently transfered into nearly background-free environment. The transfer of a molecular ion between different traps as well as the control of the molecular ions in the traps is demonstrated. Schemes, optimized for the transfer of a specific number of ions, are realized and their efficiencies are evaluated. This versatile source applicable for broad charge-to-mass ratios of externally cold and precisely positioned molecular ions can serve as a container-free target preparation device well suited for diffraction or spectroscopic measurements on individual molecular ions at high repetition rates (kHz).Comment: 11 pages, 8 figure

Hydraulic jumps: Turbulence and air bubble entrainment

A free-surface flow can change from a supercritical to subcritical flow with a strong dissipative phenomenon called a hydraulic jump. Herein the progress and development in turbulent hydraulic jumps are reviewed with a focus on hydraulic jumps operating at large Reynolds numbers typically encountered in natural streams and hydraulic structures. The key features of the turbulent hydraulic jumps are the highly turbulent flow motion associated with some intense air bubble entrainment at the jump toe. The state-of-the-art on the topic is discussed based upon recent theoretical analyses and physical data

Comparative effect of initiating metformin versus sulfonylureas on breast cancer risk in older women

Background: Several observational studies have reported that metformin may be associated with reduced risk of breast cancer95% confidence interval: 0.94, 1.6). Externally controlling for body mass index and smoking did not affect the estimates. Conclusion: The findings of this study provide no support for a reduced risk of breast cancer after initiation of metformin compared with a clinical alternative in older women. This study is limited by the relatively short follow-up time and we cannot exclude the possible benefits of long-Time metformin use on breast cancer risk.however, many of these studies were affected by time-related biases such as immortal time bias and time-window bias. This study aimed to examine the relative risk of breast cancer for older women initiating metformin versus sulfonylureas while avoiding such biases. Methods: The study cohort consisted of women aged 65+ who initiated monotherapy with metformin (n = 45,900) or sulfonylureas (n = 13,904) and were free of cancer and renal disease within 6 months before treatment initiation using 2007-2012 US Medicare claims data. We followed treatment initiators for incident breast cancer, and estimated hazard ratios using weighted Cox models. Unmeasured confounding by body mass index and smoking was further adjusted by propensity score calibration using external information from Medicare Current Beneficiary Survey 2006-2009 panels. Results: During 58,835 and 16,366 person-years of follow-up, 385 initiators of metformin treatment and 95 of sulfonylurea were diagnosed with breast cancer. Metformin initiators did not have a reduced risk of breast cancer compared with sulfonylurea initiators (hazard ratio: 1.

Differential Use of Screening Mammography in Older Women Initiating Metformin versus Sulfonylurea

Purpose: Differential use of screening mammography may lead to biased detection of breast cancer. This study aimed to compare receipt of screening mammography and the incidence of screen-detected breast cancer between metformin and sulfonylurea initiators. Methods: We used 2006-2014 US Medicare claims to identify initiators of metformin or sulfonylurea aged 65+ years continuously enrolled in Parts A/B for ≥2 years pre-initiation and ≥2 years post-initiation. We reported frequencies of screening mammograms and screen-detected breast cancer in 1 year pre-initiation among all cohort members and in 1 year post-initiation among cancer-free cohort members. Weighted screening risk differences (RDs) were estimated comparing metformin to sulfonylurea group. Results: We identified 41,436 and 13,367 initiators of metformin and sulfonylurea, 35% and 24% of which had ≥1 screening mammogram in 1 year pre-initiation (weighted RD: 6 percentage points; 95% CI: 5 to 7), respectively. The weighted RD for screen-detected breast cancer associated with metformin was 0.00 percentage points (95% CI: -0.09 to 0.09). Among cancer-free cohort members, metformin initiators had 5 percentage points (95% CI: 4 to 6) and 0.11 percentage points (95% CI: -0.02 to 0.23) absolute risk excess of screening mammography and screen-detected breast cancer in 1 year post-initiation, compared with sulfonylurea initiators, respectively. Conclusions: Metformin initiators were more likely to receive screening mammograms than sulfonylurea initiators pre- and post-initiation, indicating possible detection bias due to differential screening mammography. Researchers should be aware of the potential for more screening mammograms pre- and post-initiation when interpreting the findings of metformin on breast cancer incidence

Allocentric coding: spatial range and combination rules

International audienceWhen a visual target is presented with neighboring landmarks, its location can be determined both relative to the self (egocentric coding) and relative to these landmarks (allocentric coding). In the present study, we investigated (1) how allocentric coding depends on the distance between the targets and their surrounding landmarks (i.e. the spatial range) and (2) how allocentric and egocentric coding interact with each other across targets-landmarks distances (i.e. the combination rules). Subjects performed a memory-based pointing task toward previously gazed targets briefly superimposed (200ms) on background images of cluttered city landscapes. A variable portion of the images was occluded in order to control the distance between the targets and the closest potential landmarks within those images. The pointing responses were performed after large saccades and the reappearance of the images at their initial location. However, in some trials, the images' elements were slightly shifted (±3°) in order to introduce a subliminal conflict between the allocentric and egocentric reference frames. The influence of allocentric coding in the pointing responses was found to decrease with increasing target-landmarks distances, although it remained significant even at the largest distances (⩾10°). Interestingly, both the decreasing influence of allocentric coding and the concomitant increase in pointing responses variability were well captured by a Bayesian model in which the weighted combination of allocentric and egocentric cues is governed by a coupling prior

Bubble Entrainment, Spray and Splashing at Hydraulic Jumps

The sudden transition from a high-velocity, supercritical open channel flow into a slow-moving sub-critical flow is a hydraulic jump. Such a flow is characterised by a sudden rise of the free-surface, with some strong energy dissipation and air entrainment, waves and spray. New two-phase flow measurements were performed in the developing flow region using a large-size facility operating at large Reynolds numbers. The experimental results demonstrated the complexity of the flow with a developing mixing layer in which entrained bubbles are advected in a high shear stress flow. The relationship between bubble count rates and void fractions was non-unique in the shear zone, supporting earlier observations of some form of double diffusion process between momentum and air bubbles. In the upper region, the flow consisted primarily of water drops and packets surrounded by air. Visually significant pray and splashing were significant above the jump roller. The present study is the first comprehensive study detailing the two-phase flow properties of both the bubbly and spray regions of hydraulic jumps, a first step towards understanding the interactions between bubble entrainment and droplet ejection processes

Assessing heterogeneity of treatment effect in real-world data

Increasing availability of real-world data (RWD) generated from patient care enables the generation of evidence to inform clinical decisions for subpopulations of patients and perhaps even individuals. There is growing opportunity to identify important heterogeneity of treatment effects (HTE) in these subgroups. Thus, HTE is relevant to all with interest in patients' responses to interventions, including regulators who must make decisions about products when signals of harms arise postapproval and payers who make coverage decisions based on expected net benefit to their beneficiaries. Prior work discussed HTE in randomized studies. Here, we address methodological considerations when investigating HTE in observational studies. We propose 4 primary goals of HTE analyses and the corresponding approaches in the context of RWD: to confirm subgroup effects, to describe the magnitude of HTE, to discover clinically important subgroups, and to predict individual effects. We discuss other possible goals including exploring prognostic score- and propensity score-based treatment effects, and testing the transportability of trial results to populations different from trial participants. Finally, we outline methodological needs for enhancing real-world HTE analysis.Clinical epidemiolog

Wetting films on chemically heterogeneous substrates

Based on a microscopic density functional theory we investigate the morphology of thin liquidlike wetting films adsorbed on substrates endowed with well-defined chemical heterogeneities. As paradigmatic cases we focus on a single chemical step and on a single stripe. In view of applications in microfluidics the accuracy of guiding liquids by chemical microchannels is discussed. Finally we give a general prescription of how to investigate theoretically the wetting properties of substrates with arbitrary chemical structures.Comment: 56 pages, RevTeX, 20 Figure

Assessing inter-beach differences in semi-terrestrial arthropod assemblages on Maltese pocket sandy beaches (Central Mediterranean)

The distinctiveness of macrofaunal assemblages on different sandy beaches in the Maltese Islands was previously suggested by different single-season studies. A multi-seasonal sampling programme using pitfall trapping was implemented on four Maltese beaches to test the occurrence of this phenomenon. A total of 29,302 individuals belonging to 191 species were collected over a 2-year period, during which the beaches were sampled once per calendar season. A total of 77 species were recorded from single Maltese beaches only, of which nine were psammophiles. Non-metric multidimensional scaling analyses of pitfall trap species-abundance data resulted in a weak separation pattern, with samples grouping mainly in terms of beach and island rather than in terms of season or year of sampling, No physical variable could conclusively explain these patterns. It is concluded that although operating on Maltese beaches, macrofaunal assemblage distinctiveness is weaker than originally thought and can be attributed to the presence/absence or abundance of just a few psammophilic species. It is postulated that this phenomenon may be related to the ‘pocket beach’ nature of Maltese beaches, where headlands on either side of the beach to a large extent prevent the occurrence of longshore currents, resulting in semi-isolation of the populations of psammophilic species. A large number of single-beach records reported in this study highlight the high degree of beta diversity and spatial heterogeneity of Maltese beaches, and the conservation importance of the individual beach macrofaunal assemblages.peer-reviewe

Tight-binding parameters for charge transfer along DNA

We systematically examine all the tight-binding parameters pertinent to charge transfer along DNA. The $\pi$ molecular structure of the four DNA bases (adenine, thymine, cytosine, and guanine) is investigated by using the linear combination of atomic orbitals method with a recently introduced parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are discussed and then used for calculating the corresponding wavefunctions of the two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO and LUMO energies of the bases are in good agreement with available experimental values. Our results are then used for estimating the complete set of charge transfer parameters between neighboring bases and also between successive base-pairs, considering all possible combinations between them, for both electrons and holes. The calculated microscopic quantities can be used in mesoscopic theoretical models of electron or hole transfer along the DNA double helix, as they provide the necessary parameters for a tight-binding phenomenological description based on the $\pi$ molecular overlap. We find that usually the hopping parameters for holes are higher in magnitude compared to the ones for electrons, which probably indicates that hole transport along DNA is more favorable than electron transport. Our findings are also compared with existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table