Atomic clock performance enabling geodesy below the centimetre level.

The passage of time is tracked by counting oscillations of a frequency reference, such as Earth's revolutions or swings of a pendulum. By referencing atomic transitions, frequency (and thus time) can be measured more precisely than any other physical quantity, with the current generation of optical atomic clocks reporting fractional performance below the 10-17 level1-5. However, the theory of relativity prescribes that the passage of time is not absolute, but is affected by an observer's reference frame. Consequently, clock measurements exhibit sensitivity to relative velocity, acceleration and gravity potential. Here we demonstrate local optical clock measurements that surpass the current ability to account for the gravitational distortion of space-time across the surface of Earth. In two independent ytterbium optical lattice clocks, we demonstrate unprecedented values of three fundamental benchmarks of clock performance. In units of the clock frequency, we report systematic uncertainty of 1.4 × 10-18, measurement instability of 3.2 × 10-19 and reproducibility characterized by ten blinded frequency comparisons, yielding a frequency difference of [-7 ± (5)stat ± (8)sys] × 10-19, where 'stat' and 'sys' indicate statistical and systematic uncertainty, respectively. Although sensitivity to differences in gravity potential could degrade the performance of the clocks as terrestrial standards of time, this same sensitivity can be used as a very sensitive probe of geopotential5-9. Near the surface of Earth, clock comparisons at the 1 × 10-18 level provide a resolution of one centimetre along the direction of gravity, so the performance of these clocks should enable geodesy beyond the state-of-the-art level. These optical clocks could further be used to explore geophysical phenomena10, detect gravitational waves11, test general relativity12 and search for dark matter13-17.

Responsibility, prudence and health promotion.

This article considers the role of responsibility in public health promotion. Efforts to tackle non-communicable diseases which focus on changing individual behaviour and reducing risk factor exposure sometimes invoke individual responsibility for adopting healthy lifestyles. We provide a critical discussion of this tendency. First, we outline some key distinctions in the philosophical literature on responsibility, and indicate how responsibility is incorporated into health promotion policies in the UK. We argue that the use of some forms of responsibility in health promotion is inappropriate. We present an alternative approach to understanding how individuals can 'take responsibility' for their health, based on the concept of prudence (i.e. acting in one's interests). In this discussion, we do not prescribe or proscribe specific health promotion policies. Rather, we encourage public health professionals to consider how underlying assumptions (in this case, relating to responsibility) can shape health promotion policy, and how alternative framings (such as a shift from encouraging individual responsibility to facilitating prudence) may justify different kinds of action, for instance, shaping environments to make healthy behaviours easier, rather than using education as a tool to encourage responsible behaviour.

Faraday-Shielded dc Stark-Shift-Free Optical Lattice Clock.

We demonstrate the absence of a dc Stark shift in an ytterbium optical lattice clock. Stray electric fields are suppressed through the introduction of an in-vacuum Faraday shield. Still, the effectiveness of the shielding must be experimentally assessed. Such diagnostics are accomplished by applying high voltage to six electrodes, which are grounded in normal operation to form part of the Faraday shield. Our measurements place a constraint on the dc Stark shift at the 10^{-20} level, in units of the clock frequency. Moreover, we discuss a potential source of error in strategies to precisely measure or cancel nonzero dc Stark shifts, attributed to field gradients coupled with the finite spatial extent of the lattice-trapped atoms. With this consideration, we find that Faraday shielding, complemented with experimental validation, provides both a practically appealing and effective solution to the problem of dc Stark shifts in optical lattice clocks.

#cutting: Non-suicidal self-injury (NSSI) on Instagram.

BACKGROUND: Social media presents an important means for social interaction, especially among adolescents, with Instagram being the most popular platform in this age-group. Pictures and communication about non-suicidal self-injury (NSSI) can frequently be found on the internet. METHODS: During 4 weeks in April 2016, n = 2826 (from n = 1154 accounts) pictures which directly depicted wounds on Instagram were investigated. Those pictures, associated comments, and user accounts were independently rated for content. Associations between characteristics of pictures and comments as well as weekly and daily trends of posting behavior were analyzed. RESULTS: Most commonly, pictures depicted wounds caused by cutting on arms or legs and were rated as mild or moderate injuries. Pictures with increasing wound grades and those depicting multiple methods of NSSI generated elevated amounts of comments. While most comments were neutral or empathic with some offering help, few comments were hostile. Pictures were mainly posted in the evening hours, with a small peak in the early morning. While there was a slight peak of pictures being posted on Sundays, postings were rather evenly spread across the week. CONCLUSIONS: Pictures of NSSI are frequently posted on Instagram. Social reinforcement might play a role in the posting of more severe NSSI pictures. Social media platforms need to take appropriate measures for preventing online social contagion.

Hyperpolarizability and Operational Magic Wavelength in an Optical Lattice Clock.

Optical clocks benefit from tight atomic confinement enabling extended interrogation times as well as Doppler- and recoil-free operation. However, these benefits come at the cost of frequency shifts that, if not properly controlled, may degrade clock accuracy. Numerous theoretical studies have predicted optical lattice clock frequency shifts that scale nonlinearly with trap depth. To experimentally observe and constrain these shifts in an ^{171}Yb optical lattice clock, we construct a lattice enhancement cavity that exaggerates the light shifts. We observe an atomic temperature that is proportional to the optical trap depth, fundamentally altering the scaling of trap-induced light shifts and simplifying their parametrization. We identify an "operational" magic wavelength where frequency shifts are insensitive to changes in trap depth. These measurements and scaling analysis constitute an essential systematic characterization for clock operation at the 10^{-18} level and beyond.

Psychosocial interventions for children and adolescents after man-made and natural disasters: a meta-analysis and systematic review.

Children and adolescents are a vulnerable group to develop post-traumatic stress symptoms after natural or man-made disasters. In the light of increasing numbers of refugees under the age of 18 years worldwide, there is a significant need for effective treatments. This meta-analytic review investigates specific psychosocial treatments for children and adolescents after man-made and natural disasters. In a systematic literature search using MEDLINE, EMBASE and PsycINFO, as well as hand-searching existing reviews and contacting professional associations, 36 studies were identified. Random- and mixed-effects models were applied to test for average effect sizes and moderating variables. Overall, treatments showed high effect sizes in pre-post comparisons (Hedges' g = 1.34) and medium effect sizes as compared with control conditions (Hedges' g = 0.43). Treatments investigated by at least two studies were cognitive-behavioural therapy (CBT), eye movement desensitization and reprocessing (EMDR), narrative exposure therapy for children (KIDNET) and classroom-based interventions, which showed similar effect sizes. However, studies were very heterogenic with regard to their outcomes. Effects were moderated by type of profession (higher level of training leading to higher effect sizes). A number of effective psychosocial treatments for child and adolescent survivors of disasters exist. CBT, EMDR, KIDNET and classroom-based interventions can be equally recommended. Although disasters require immediate reactions and improvisation, future studies with larger sample sizes and rigorous methodology are needed.

Anomalous Broadening in Driven Dissipative Rydberg Systems.

We observe interaction-induced broadening of the two-photon 5s-18s transition in ^{87}Rb atoms trapped in a 3D optical lattice. The measured linewidth increases by nearly 2 orders of magnitude with increasing atomic density and excitation strength, with corresponding suppression of resonant scattering and enhancement of off-resonant scattering. We attribute the increased linewidth to resonant dipole-dipole interactions of 18s atoms with blackbody induced population in nearby np states. Over a range of initial atomic densities and excitation strengths, the transition width is described by a single function of the steady-state density of Rydberg atoms, and the observed resonant excitation rate corresponds to that of a two-level system with the measured, rather than natural, linewidth. The broadening mechanism observed here is likely to have negative implications for many proposals with coherently interacting Rydberg atoms.

Self-monitoring has no adverse effect on disordered eating in adults seeking treatment for obesity.

OBJECTIVES: Although monitoring is considered a key component of effective behaviour change, the development of apps has allowed consumers to constantly evaluate their own diet, with little examination of what this might mean for eating behaviour. The aim of this study was to investigate whether self-monitoring of diet using the app MyFitnessPal or daily self-weighing increases the reported occurrence of eating disorders in adults with overweight/obesity following a weight loss programme. METHODS: Two hundred fifty adults with body mass index ≥ 27 kg/m2 received diet and exercise advice and were randomized to one of four monitoring strategies (daily self-weighing, MyFitnessPal, brief monthly consults or self-monitoring hunger) or control for 12 months. The Eating Disorder Examination Questionnaire 6.0 was used to assess eating disorder symptoms and behaviours for the previous 28 d at 0 and 12 months. RESULTS: There were no significant differences in the global Eating Disorder Examination Questionnaire score or the subscales between those in the four monitoring groups and the control at 12 months (all p ≥ 0.164), nor were there differences in binge eating, self-induced vomiting, laxative misuse or excessive exercise at 12 months (p ≥ 0.202). The overall prevalence of one or more episodes of binge eating was 53.6% at baseline and 50.6% at 12 months, with no change over time (p = 0.662). CONCLUSIONS: There was no evidence that self-monitoring, including using diet apps like MyFitnessPal or daily self-weighing, increases the reported occurrence of eating disorder behaviours in adults with overweight/obesity who are trying to lose weight.

Inhibitin: a specific inhibitor of sodium/sodium exchange in erythrocytes.

An inhibitor of ouabain-insensitive sodium/sodium exchange in erythrocytes has been isolated from leukemic promyelocytes. To explore the specific effects of this inhibitor, named inhibitin, sodium transport experiments were carried out in human erythrocytes. Inhibitin reduced ouabain-insensitive bidirectional sodium transport. It did not change net sodium fluxes, had no significant effect on rubidium influx, and did not inhibit sodium-potassium-ATPase activity. The inhibitory effect of inhibitin was studied on sodium/sodium exchange and on sodium/lithium countertransport in 140 mM sodium and in sodium-free media. In the presence of sodium, inhibitin reduced sodium and lithium efflux to that observed in sodium-free medium. Inhibitin showed no reduction in sodium or lithium efflux when sodium was replaced by choline chloride or Mg2+. When inhibitin was combined with one or more of the other transport inhibitors (i.e., ouabain, furosemide, or bumetanide and amiloride), its inhibitable component remained distinct and it did not overlap with that of the other inhibitors. These studies show that inhibitin is a specific inhibitor of carrier-mediated sodium/sodium exchange and sodium/lithium countertransport processes in human erythrocytes.

Abnormal vitamin D metabolism, intestinal calcium transport, and bone calcium status in the spontaneously hypertensive rat compared with its genetic control.

Abnormalities of intestinal calcium absorption and the vitamin D axis in the spontaneously hypertensive rat (SHR) are controversial. The present report documents a reduction in circulating 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the 12-14-wk-old male SHR with evidence of its functional significance. Both plasma 1,25(OH)2D3 and mucosa-to-serosa duodenal calcium flux (Jm-s), measured by the Ussing chamber, were significantly lower (approximately 60% of value in Wistar-Kyoto rats [WKY]) in SHR on both normal (1%) and low (0.1%) calcium diets than in corresponding control WKY. Low dietary calcium increased both 1,25(OH)2D3 and Jm-s by approximately 80% in SHR and WKY, with levels of both parameters rising in the SHR to levels found in the WKY under baseline conditions. The latter fact suggests the improbability of intestinal resistance to the action of 1,25(OH)2D3 in the SHR. Plasma 25-hydroxyvitamin D3 (25(OH)D3) was not significantly different between the strains. Intraperitoneal 1,25(OH)2D3 increased Jm-s in 12-14-wk-old SHR to levels observed in equivalent WKY. In 20-24-wk-old SHR, calcium deprivation was associated with significantly reduced Jm-s compared with equivalent WKY. Bone density and bone calcium content in 20-30-wk-old SHR were significantly reduced. In summary, we provide evidence that the SHR was unable to sustain appropriate circulating levels of 1,25(OH)2D3, an impairment which resulted in reduced duodenal calcium absorption.

Endosperm Development in Barley: Microtubule Involvement in the Morphogenetic Pathway.

An immunofluorescence study of sectioned barley endosperm imaged by confocal laser scanning microscopy provided three-dimensional data on the relationship of microtubules to the cytoplasm, nuclei, and cell walls during development from 4 to 21 days after pollination (DAP). Microtubules play an important role throughout endosperm ontogeny. The syncytium is organized into units of nuclear-cytoplasmic domains by nuclear-based radial microtubule systems that appear to control the pattern of the first anticlinal walls at 5 to 6 DAP. After 7 DAP, phragmoplasts of two origins (interzonal and cytoplasmic) guide wall formation. Large compartments formed by the "free growing" walls in association with cytoplasmic phragmoplasts formed adventitiously at interfaces of opposing microtubule systems are subsequently subdivided by interzonal phragmoplast/cell plates to give rise to the starchy endosperm. During development of the aleurone layer from 8 to 21 DAP, the microtubule cycle is typical of plant histogenesis; cortical microtubules are hooplike, and preprophase bands of microtubules predict the division plane.

Differences in Activation and Deactivation in Children with Sickle Cell Disease Compared with Demographically Matched Controls.

BACKGROUND AND PURPOSE: Declines in both functional activation and functional connectivity have been reported in patients with sickle cell disease. In this study, we derived the functional and default mode responses to a word stem paradigm in age-, ethnicity-, and background-matched subjects with sickle cell disease and control groups, with the aim of testing whether both networks were similarly attenuated and whether the changes were related to physiologic parameters that characterize sickle cell disease. MATERIALS AND METHODS: Both the functional and default mode responses were obtained from age- and background-matched controls and the sickle cell population by using a visually presented word stem paradigm on a 3T scanner. RESULTS: We observed an attenuated response to both activation and deactivation in the sickle cell disease group. There were no significant differences in the activation response between the 2 groups for the contrast control > sickle cell disease; however, significant differences were observed in the medial parietal cortex, the auditory cortex, and the angular gyrus for the default mode. For the sickle cell group, a significant correlation between the activation z scores and the physiologic parameters was observed; for the deactivation, the results were not significant but the trend was similar. CONCLUSIONS: The results indicate that the physiologic parameters modulate the activation in the expected fashion, but that the effect was weaker for deactivation. Given that significant differences between the 2 groups were only seen for deactivation, additional factors must modulate the deactivation in sickle cell disease.

Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders.

The peripheral-type benzodiazepine receptor is a mitochondrial protein expressed at high levels in steroid synthesizing tissues, including the glial cells of the brain. Peripheral-type benzodiazepine receptor binds cholesterol with high affinity and is a key element of the cholesterol mitochondrial import machinery responsible for supplying the substrate cholesterol to the first steroidogenic enzyme, thus initiating and maintaining neurosteroid biosynthesis. Neurosteroid formation and metabolism of steroid intermediates are critical components of normal brain function. Peripheral-type benzodiazepine receptor also binds with high affinity various classes of compounds. Upon ligand activation peripheral-type benzodiazepine receptor-dependent cholesterol transport into mitochondria is accelerated leading in increased formation of neuroactive steroids. These steroids, such as allopregnanolone, have been shown to be involved in various neurological disorders, such as anxiety and mood disorders. Thus, peripheral-type benzodiazepine receptor drug ligand-induced neuroactive steroid formation offers a means to regulate brain dysfunction. Peripheral-type benzodiazepine receptor basal expression is upregulated in a number of neuropathologies, including gliomas and neurodegenerative disorders, as well as in various forms of brain injury and inflammation. In Alzheimer's disease pathology neurosteroid biosynthesis is altered and a decrease in the intermediate 22R-hydroxycholesterol levels is observed. This steroid was found to exert neuroprotective properties against beta-amyloid neurotoxicity. Based on this observation, a stable spirostenol derivative showing to display neuroprotective properties was identified, suggesting that compounds developed based on critical intermediates of neurosteroid biosynthesis could offer novel means for neuroprotection. In conclusion, changes in peripheral-type benzodiazepine receptor and neurosteroid levels are part of the phenotype seen in neuropathology and neurological disorders and offer potential targets for new therapies.

Evaluation of irradiation-plus-urethan-induced murine leukemia virus "release" using a new method for quantitation of oncornaviruses in tissues.

The quantity of C-type RNA tumor viruses in homogenate-sonicates of thymus-bone marrow tissues of C57BL/6J and RFM/Un mice 10 days after irradiation (X-rays or gamma-rays)-plus-urethan treatments is no greater than that in thymus-bone marrow homogenates from nontreated control mice. These results indicate that the leukemogenic activity, shown to be present in such thymus-bone marrow homogenates at this time after irradiation-plus-urethan treatment, is not due to change in quantity of C-type viruses as has been proposed. Virus quantity in tissues was evaluated by a new procedure that includes use of a microchamber with the sides situated on rotor radii so as to produce a uniform virus-containing sediment of tissue homogenate-sonicate that is evaluated by electron microscopic examination of this sections cut perpendicular to the membrane surface. Samples containing as little as 105 to 106 viruses can be relatively easily counted. Semipurified or purified viruses can also be counted after mixing with a tissue homogenate-bovine serum albumin diluent.

Release of a sodium transport inhibitor (inhibitin) from cultured human cancer cells.

In this study we investigated whether the sodium transport inhibitor, inhibitin, originally isolated from leukemic promyelocytes, was also elaborated by some other neoplastic cells in culture. Like culture medium from the leukemic promyelocytes (HL60), the media from two other leukemic cell lines (erythroblasts K562 and monoblasts U937) also showed significant inhibitory activity on ouabain-insensitive sodium efflux rate constant in normal erythrocytes. Similarly, culture media from three neoplastic cell lines (H.Ep2, MRC5, and HX99) also showed significant inhibitin-like inhibitory activity. Using high-performance liquid chromatography to isolate inhibitin, culture media from HL60 and H.Ep2 cells were identically treated, and inhibitin isolated from H.Ep2 cells had the same retention time as that shown by promyelocyte inhibitin. H.Ep2 inhibitin reduced ouabain- and bumetanide-insensitive sodium efflux rate constant from 0.1510 +/- 0.0275 (SD) to 0.0988 +/- 0.0110 (P less than 0.005). Like promyelocyte inhibitin, H.Ep2 inhibitin reduced sodium efflux and influx by equivalent amounts suggesting thereby that it is a sodium/sodium exchange inhibitor. These studies show that a factor exhibiting inhibitory activity on sodium/sodium exchange is secreted by a variety of leukemic and neoplastic cells in culture.

Isolation and characterization of rat alpha-lactalbumin: a glycoprotein.

alpha-Lactalbumin was purified to homogeneity from rat milk. Rat alpha-lactalbumin, in contrast to other alpha-lactalbumins, is a glycoprotein and exhibits an abnormally high molecular weight when obtained by gel filtration or electrophoresis in sodium dodecyl sulfate. The molecular weight by sedimentation equilibrium is 15 400 +/- 5% and of the reduced and alkylated protein is 16 000 when determined by thin-layer chromatography in 6 M guanidine hydrochloride. At least, three major charge forms, all containing carbohydrate and active in the lactose synthetase reaction were demonstrated. The amino acid composition reveals a high proline content which is reflected in a low alpha-helical content.

Adsorption of arsenic(V) by activated carbon prepared from oat hulls.

The efficiency of self-manufactured activated carbon (AC) produced from oat hulls in adsorbing arsenic(V) was tested in a batch reactor. The results indicated that the adsorptive capacity of AC was affected by initial pH value, with adsorption capacity decreasing from 3.09 to 1.57 mg As g(-1) AC when the initial pH values increased from 5 to 8. A modified linear driving force model conjugated with a Langmuir isotherm was created to describe the study's kinetics. The test results show that rapid adsorption and slow adsorption exist simultaneously when AC is used to remove arsenic(V).

Adherence to hunger training using blood glucose monitoring: a feasibility study.

BACKGROUND: "Hunger training", which aims to teach people to eat only when blood glucose is below a set target, appears promising as a weight loss strategy. As the ability of participants to adhere to the rigorous protocol has been insufficiently described, we sought to determine the feasibility of hunger training, in terms of retention in the study, adherence to measuring blood glucose, and eating only when blood glucose concentrations are below a set level of 4.7 mmol/L. METHOD: We undertook a two-week feasibility study, utilising an adaptive design approach where the specific blood glucose cut-off was the adaptive feature. A blood glucose cut-off of 4.7 mmol/L (protocol A) was used for the first 20 participants. A priori we decided that if interim analysis revealed that this cut-off did not meet our feasibility criteria, the remaining ten participants would use an individualised cut-off based on their fasting glucose concentrations (protocol B). RESULTS: Retention of the participants in the study was 97 % (28/29 participants), achieving our criterion of 85 %. Participants measured their blood glucose before 94 % (95 % CI 91, 98) of eating occasions (criterion 80 %). However, participants following protocol A, which used a standard blood glucose cut-off of 4.7 mmol/L, were only able to adhere to eating when blood glucose was below the prescribed level 66 % of the time, below our within-person criterion of 75 %. By contrast, those participants following protocol B (individualised cut-off) adhered to the eating protocol 84 % of the time, a significant (p = 0.010) improvement over protocol A. CONCLUSION: Hunger training appears to be a feasible method, at least in the short-term, when an individualised fasting blood glucose is used to indicate that a meal can begin.

Quantum simulation. Two-dimensional superexchange-mediated magnetization dynamics in an optical lattice.

The interplay of magnetic exchange interactions and tunneling underlies many complex quantum phenomena observed in real materials. We study nonequilibrium magnetization dynamics in an extended two-dimensional (2D) system by loading effective spin-1/2 bosons into a spin-dependent optical lattice and use the lattice to separately control the resonance conditions for tunneling and superexchange. After preparing a nonequilibrium antiferromagnetically ordered state, we observe relaxation dynamics governed by two well-separated rates, which scale with the parameters associated with superexchange and tunneling. With tunneling off-resonantly suppressed, we observe superexchange-dominated dynamics over two orders of magnitude in magnetic coupling strength. Our experiment will serve as a benchmark for future theoretical work as the detailed dynamics of this 2D, strongly correlated, and far-from-equilibrium quantum system remain out of reach of current computational techniques.

Seroprevalence and clinical manifestations of HIV-1 infection in Kananga, Zaire.

The objective of this study was to ascertain the seroprevalence and clinical manifestations of HIV-1 infection in Kananga, Zaire, in 1988. In the city of Kananga (population 300,000), eight out of 258 (3.1%) consecutive, asymptomatic, prenatal patients were seropositive. Of 452 consecutive blood donors at our institution, eight (1.8%) were seropositive. Sixty per cent of 299 consecutive, seropositive, clinically ill adults presented with chronic diarrhea, fever or weight loss (Centers for Disease Control group IVA). The male-to-female ratio of symptomatic, seropositive patients was 1:1.5. Women who indicated on a socioeconomic questionnaire that they engaged in 'commerce' (meaning possibly that they were petty traders, wholesale brokers, or prostitutes) were more often HIV-seropositive than women who did not engage in 'commerce' (P less than 0.001).