Test of Special Relativity Using a Fiber Network of Optical Clocks.

Phase compensated optical fiber links enable high accuracy atomic clocks separated by thousands of kilometers to be compared with unprecedented statistical resolution. By searching for a daily variation of the frequency difference between four strontium optical lattice clocks in different locations throughout Europe connected by such links, we improve upon previous tests of time dilation predicted by special relativity. We obtain a constraint on the Robertson-Mansouri-Sexl parameter |α|≲1.1×10^{-8}, quantifying a violation of time dilation, thus improving by a factor of around 2 the best known constraint obtained with Ives-Stilwell type experiments, and by 2 orders of magnitude the best constraint obtained by comparing atomic clocks. This work is the first of a new generation of tests of fundamental physics using optical clocks and fiber links. As clocks improve, and as fiber links are routinely operated, we expect that the tests initiated in this Letter will improve by orders of magnitude in the near future.

Mechanism of action of ethylene sulfite and vinylene carbonate electrolyte additives in LiNi1/3Mn1/3Co1/3O2/graphite pouch cells: electrochemical, GC-MS and XPS analysis.

The role of ethylene sulfite used either alone or in combination with VC in LiNi1/3Mn1/3Co1/3O2 (NMC)/graphite pouch cells was studied by correlating data from differential capacity (dQ/dV) analysis, gas chromatography/mass spectroscopy (GC-MS), theoretical calculations, ultrahigh precision coulometry, storage experiments and X-ray photoelectron spectroscopy. For cells containing VC alone, the electrochemical performance and gas production were greatly improved, compared to cells without VC, due to the formation of more stable and protective SEI films at both electrode surfaces by a polymer of VC. For cells with ES alone, a vigorous reactivity was observed due to preferential reduction that also generated large amounts of gas during formation. The dramatic decrease in electrochemical performance as well as the continuous production of gas during cycling in cells with ES was explained by the formation of a very thin and ineffective SEI film at the NMC surface. The suppression of the vigorous reaction of ES in cells with both ES and VC occurred because the solvation energy of Li(+) by VC is smaller than that of EC so VC is reduced first during formation. During charge-discharge cycling, a slow consumption of ES occurred and different sulfur species were observed on the electrodes when VC was combined with ES. SEI film formation processes and SEI composition were therefore dominated by VC and the electrochemical performance of cells with both VC and ES were similar compared to those of cells with VC alone.

Opportunities to prevent and manage undernutrition to amplify efforts to end TB.

The bidirectional relationship between TB and nutrition is well recognized - primary undernutrition is a risk factor for developing TB disease, while TB results in wasting. Although nutrition support is acknowledged as an important intervention in TB programmes, it is seldom afforded commensurate priority for action. TB incidence and deaths worldwide are falling too slowly to meet WHO End TB Strategy milestones, and the number of undernourished people is increasing, likely to be further exacerbated by the ongoing COVID-19 pandemic. Undernutrition needs to be more urgently and intensively addressed. This is especially true for the WHO South-East Asia Region, where the high rates of undernutrition are a key driver of the TB epidemic. The evidence base has been sufficiently robust for clear and workable programmatic guidance to be formulated on assessment, counselling and interventions for TB patients. Many high-burden countries have developed policies addressing TB and nutrition. Gaps in research to date have frustrated the development of more refined programmatic approaches related to addressing TB and malnutrition. Future research can be shaped to inform targeted, actionable policies and programmes delivering dual benefits in terms of undernutrition and TB. There are clear opportunities for policy-makers to amplify efforts to end TB by addressing undernutrition.

Optical interferometry-based array of seafloor environmental sensors using a transoceanic submarine cable.

Optical fiber-based sensing technology can drastically improve Earth observations by enabling the use of existing submarine communication cables as seafloor sensors. Previous interferometric and polarization-based techniques demonstrated environmental sensing over cable lengths up to 10,500 kilometers. However, measurements were limited to the integrated changes over the entire length of the cable. We demonstrate the detection of earthquakes and ocean signals on individual spans between repeaters of a 5860-kilometer-long transatlantic cable rather than the whole cable. By applying this technique to the existing undersea communication cables, which have a repeater-to-repeater span length of 45 to 90 kilometers, the largely unmonitored ocean floor could be instrumented with thousands of permanent real-time environmental sensors without changes to the underwater infrastructure.

Comparing ultrastable lasers at 7 × 10-17 fractional frequency instability through a 2220 km optical fibre network.

Ultrastable lasers are essential tools in optical frequency metrology enabling unprecedented measurement precision that impacts on fields such as atomic timekeeping, tests of fundamental physics, and geodesy. To characterise an ultrastable laser it needs to be compared with a laser of similar performance, but a suitable system may not be available locally. Here, we report a comparison of two geographically separated lasers, over the longest ever reported metrological optical fibre link network, measuring 2220 km in length, at a state-of-the-art fractional-frequency instability of 7 × 10-17 for averaging times between 30 s and 200 s. The measurements also allow the short-term instability of the complete optical fibre link network to be directly observed without using a loop-back fibre. Based on the characterisation of the noise in the lasers and optical fibre link network over different timescales, we investigate the potential for disseminating ultrastable light to improve the performance of remote optical clocks.

Comparison of selected skin decontaminant products and regimens against VX in domestic swine.

An anesthetized domestic swine model was used to compare the efficacy and cross-contamination potential of selected skin decontaminant products and regimens against the chemical warfare agent, VX. Animals topically exposed to 2x, 3x or 5x LD(50) VX showed typical signs of organophosphate nerve agent poisoning, including miosis, salivation, mastication, dysrhythmias, and respiratory distress prior to death. Animals were exposed to 5x LD(50) VX and then decontaminated 45 min later with the reactive skin decontamination lotion (RSDL), Fuller's earth (FE), 0.5% hypochlorite, or soapy water. Survival was 100% when the reactive skin decontamination lotion or FE was utilized, although 50% of Fuller's earth-decontaminated animals exhibited serious signs of VX poisoning. Decontamination of VX-treated animals with 0.5% hypochlorite was less effective but also increased survival. Soapy water was ineffective in preventing lethality. Blood cholinesterase levels were not predictive of clinical outcome in decontaminated animals. The potential of "decontaminated" VX in open wounds to cause poisoning was assessed by vigorously mixing 5x LD(50) VX with the test decontaminants for 5 min and then placing the mixture onto a full-thickness skin wound. Soapy water was ineffective in preventing lethality. Although treatment with dry Fuller's earth prevented death and all signs of organophosphate poisoning, a significant proportion of treated animals decontaminated with Fuller's earth in aqueous suspension exhibited serious signs of organophosphate poisoning, suggesting that live agent may be desorbed from Fuller's earth when it is exposed to a liquid environment. Animals treated with reactive skin decontamination lotion or 0.5% hypochlorite-VX mixtures showed no signs of organophosphate poisoning during the 6- h test period.

[Conclusions and recommendations of a WHO expert consultation meeting on iron supplementation for infants and young children in malaria endemic areas]. / Conclusions et recommandations à l'issue de la consultation de l'OMS sur la lutte contre la carence martiale chez le nourrisson et le jeune enfant dans les pays d'endémie palustre.

This article presents the results of an expert consultation meeting aimed at evaluating the safety and public health implications of administering supplemental iron to infants and young children in malaria-endemic areas. Participants at this meeting that took place in Lyon, France on June 12-14, 2006 reached consensus on several important issues related to iron supplementation for infants and young children in malaria-endemic areas. The conclusions in this report apply specifically to regions where malaria is endemic.

Note: A high-performance, low-cost laser shutter using a piezoelectric cantilever actuator.

We report the design and characterization of an optical shutter based on a piezoelectric cantilever. Compared to conventional electro-magnetic shutters, the device has intrinsically low power and is acoustically quiet. The cantilever position is controlled by a high-voltage op-amp circuit for easy tuning of the range of travel, and mechanical slew rate, which enables a factor of 30 reduction in mechanical noise compared to a rapidly switched device. We achieve shuttering rise and fall times of 11 µs, corresponding to mechanical slew rates of 1.3 ms-1, with a timing jitter of less than 1 µs. When used to create optical pulses, we achieve minimum pulse durations of 250 µs. The reliability of the shutter was investigated by operating continuously for one week at 10 Hz switching rate. After this period, neither the shutter delay or actuation speed had changed by a measurable amount.

In vitro cytotoxicity of poly(amidoamine)s: relevance to DNA delivery.

We have examined the cytotoxicity of a number of poly(amidoamine) polymers which have been proposed for use as DNA delivery systems and compared them to the charged polyamino acid polylysine. Most of the poly(amidoamine)s tested were shown to be remarkably non-toxic to both HepG2 and HL60 cell lines. However, one of the structures (NG30, co-monomers methylene bisacrylamide, dimethylethylene diamine) did show cytotoxicity similar to that of polylysine. A second PAA structure (NG37, NG38, NG39, co-monomers bisacryloyl piperazine, 2-methyl piperazine) showed mild cytotoxicity towards both cell lines, related to the degree of polymerisation. The results support the idea that the cytotoxicity of polycations has a strong structural basis rather than being an effect due only to charge. As a consequence of their general reduced level of cytotoxicity, poly(amidoamine)s appear to have possible advantages for complexation with DNA over some other cationic polymers as a key component of DNA delivery systems.

Polymer chemical structure is a key determinant of physicochemical and colloidal properties of polymer-DNA complexes for gene delivery.

Polyplexes are now emerging as potentially useful vectors for gene therapy. To improve our understanding of how the chemical structure of the polymer affects the properties of these systems, a series of structurally related polymers, the linear poly(amidoamine)s (PAAs), have been examined for their abilities to form complexes with DNA. Structure-dependent differences in DNA binding are shown by gel electrophoretic retardation of DNA and thermal transition analyses. Two PAAs, NG28 and NG30, stand out as having high affinity DNA binding characteristics, similar to the model homopolypeptide, poly-L-lysine. In addition, differences in complex formation, particle size and surface charge are displayed for the different polymer-DNA systems. Electron microscopy studies showed that the polymers condensed DNA into similar unit structures but only complexes with NG30 did not undergo agglomeration. This was attributed to an excess of complexed polymer forming a shell of uncomplexed polymer chain segments around a condensed DNA-polymer core. The transfection activities of these polymer complexes differ greatly, and some of these differences can be explained in a multifactorial way by the physicochemical and colloidal properties. It is concluded that polymer chemical structure dictates the apparent affinity of DNA binding, and also several of the important colloidal characteristics of the resulting complexes.

Short-term effect of epidermal growth factor (EGF) on sodium and glucose cotransport of isolated jejunal epithelial cells.

This study was undertaken to assess the short-term effects of EGF on sodium and glucose uptake, glucose metabolism and Na+/K(+)-ATPase activity in isolated enterocytes of rats. Jejunal cells exposed to EGF had a significantly greater total uptake of sodium compared to controls after 6 min. Kinetic analysis of glucose transport across BBMV's demonstrated similar Km values but a significant increase of the Vmax in vesicles prepared from cells first exposed to EGF as compared to controls. EGF was also associated with a significant increase in glucose metabolism of jejunal enterocytes after 15 min. The activity of Na+/K(+)-ATPase increased in jejunal enterocytes exposed to EGF. The increase in Na+/K(+)-ATPase activity of the cells following EGF exposure was not accompanied by an increase in immunodetectable total or assembled Na+/K(+)-ATPase protein. EGF's effect on enzyme activity was abolished by removing NaCl from the incubation solution, and by preincubating the enterocytes with phlorizin prior to addition of EGF. Preincubation with amiloride did not inhibit the effect of EGF on Na+/K(+)-ATPase. The results confirm that EGF promotes uptake of both sodium and glucose by the jejunal mucosal cells, and suggest the effect of EGF on glucose and sodium is mediated through the brush-border membrane glucose-sodium transporter. The increase in Na+/K(+)-ATPase activity that occurs with EGF appears to be secondary to a rise in intracellular Na+ concentration. The short-term effects of EGF on glucose and sodium transport by the small intestine may have potential therapeutic implications.

Early development of accelerated graft coronary artery disease: risk factors and course.

OBJECTIVES: This study assessed the time of first appearance of angiographic graft coronary artery disease in relation to clinical and laboratory variables and clinical events in heart transplant recipients. BACKGROUND: Graft coronary artery disease is the main factor limiting long-term survival after heart transplantation, and it is important to understand its natural history. METHODS: One hundred thirty-nine consecutive patients who developed angiographic coronary artery disease after heart transplantation were classified according to early (< or = 2 years) versus late (> 2 years) posttransplantation initial detection of coronary artery disease. These subgroups were analyzed for differences in clinical and laboratory demographics, incidence of progression to ischemic events and incidence of antecedent cytomegalovirus infection. RESULTS: The early-onset group (64 patients) had more rapid progression to ischemic events than the late-onset group (75 patients), with 59% of the late group and only 35% of the early group free from ischemic events by 5 years after initial detection (p = 0.02), but there were no significantly correlated clinical or laboratory predictors of ischemic events. The early group had a significantly higher incidence of antecedent cytomegalovirus infection. CONCLUSIONS: We conclude that 1) accelerated graft coronary artery disease develops at variable times after heart transplantation; 2) the early appearance of graft coronary artery disease may be a marker of intrinsically more aggressive disease; 3) cytomegalovirus infection is associated with earlier onset of graft coronary artery disease. Patients with early development of graft coronary artery disease should potentially be given priority for interventional strategies as they are developed.

In vivo skin absorption and distribution of the nerve agent VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) in the domestic white pig.

The purpose of this study was to characterize the skin absorption and distribution of VX (O-ethyl-S-[2 (diisopropylamino)ethyl] methylphosphonothioate) in the domestic pig in order to evaluate the animal as a potential model for assessing pretreatments against toxic anti-cholinesterase compounds. A liquid droplet (equivalent to a 2 x LD50 dose) of radiolabelled VX was applied to the inner ear-skin of each anaesthetized animal. Blood and tissue samples (liver, lung, kidney, heart and skin exposure sites) were obtained post-mortem. The amount of radioactivity in each sample was measured by liquid scintillation counting, from which the skin absorption rate and dose distribution of VX were calculated. A substantial proportion (22 +/- 3%) of the applied dose remained within the skin at the site of application. It is conceivable that strategies to minimize or remove this reservoir may be of benefit in the early treatment of VX-exposed casualties. Image analysis of autoradiographs of exposed skin sites indicated that each milligram of radioactive VX covered an area of 1.2 +/- 0.5 cm2. The average skin absorption rate of 14C-VX was 661 +/- 126 microg/cm2 per hour. Comparison of these data with previous studies suggests that human skin is less permeable to VX than pig skin, but VX spreads over a greater surface area when applied to human skin. Thus, paradoxically, while pig-ear skin is more permeable than human skin, the difference in skin surface spreading may lead to the absorption of an equivalent systemic dose.

Differences in DNA fragmentation following transient cerebral or decapitation ischemia in rats.

The time course of appearance of cells with DNA damage was studied in rats following transient severe forebrain ischemia. This DNA damage could be detected by in situ end-labeling on brain sections. The breaks in DNA appeared selectively by day 1 in the striatum and later in the CA1 region of the hippocampus. It was possible by double labeling to show that there was no DNA damage in astrocytes. The DNA breaks consisted of laddered DNA fragments indicative of an ordered apoptotic type of internucleosomal cleavage, which persisted without smearing for up to 7 days of reperfusion. In contrast, the DNA breaks following ischemia induced by decapitation were random and, after gel electrophoresis, consisted of smeared fragments of multiple sizes. There was some early regional cellular death, restricted to the dentate of the hippocampus, prior to the pannecrotic degeneration. It is concluded that transient forebrain ischemia leads to a type of neuronal destruction that is not random necrosis but that shares some component of the apoptotic cell death pathway.

A novel peptide designed for sensitization of terbium (III) luminescence.

Several synthetic peptides, modelled from a Ca(2+)-binding loop of the EF-hand family of proteins, were prepared containing cysteine residues. The peptide, GDKNADGFICFEEL, was labelled covalently at the cysteine residue (loop position 9) with iodoacetamidosalicylic acid. This novel conjugate is a metal-binding loop containing a salicylic acid side chain that could not only chelate Tb3+ in conjunction with the other chelating groups in the sequence, but could also sensitize Tb3+ luminescence. The loop had a high Tb3+ affinity, with stoichiometric binding observed under experimental conditions. The luminescence from the Tb(3+)-peptide complex was more than 10-fold greater than the luminescence reported from a related peptide which contained Trp as the Tb3+ donor at loop position 7. This peptide has significant potential for use in lanthanide-based time-resolved luminescence immunoassays.

Vitamin and iron status in new vegetarians.

This study assessed the biochemical status of a number of vitamins and iron in a group of new vegetarians. Values were compared with a group of omnivores of similar age. Satisfactory to high levels of serum folate, vitamin E, and riboflavin were found, and all were significantly higher in vegetarians than omnivores. Thiamin status was satisfactory in both groups although a small but statistically significant difference in favor of the omnivores was found. Serum vitamin B-12 was significantly lower in vegetarians, and iron status as measured by serum ferritin was very significantly lower in vegetarians. Pyridoxine status was similar in both groups. A number of sex differences were found in the vegetarian sample. New vegetarian women appear to be at particular risk of developing low iron stores.

Lactose malabsorption in Australian Aboriginal children.

The purpose of this study was to determine the prevalence of lactose malabsorption in healthy full-blood Australian Aboriginal children. Sixty-three Aboriginal subjects and forty-six non-Aboriginal controls ranging in age from six to 14 years were tested using the breath hydrogen method. Seventy percent of the Aboriginal subjects were found to be lactose malabsorbers and 9% of the controls. The results provide strong evidence that the majority of full-blood Aboriginal children are lactose malabsorbers and that the characteristic is well-established by 6-7 years of age, in common with most other non-Western populations.

Efficacy of a vitamin A-fortified wheat-flour bun on the vitamin A status of Filipino schoolchildren.

BACKGROUND: Wheat flour is a possible food vehicle for vitamin A fortification. OBJECTIVE: This study assessed the efficacy of consumption of a vitamin A-fortified wheat-flour bun (pandesal) on the vitamin A status of school-age children. DESIGN: This was a double-masked clinical trial conducted in 396 and 439 children aged 6-13 y attending 4 rural schools in the Philippines. The children were randomly assigned to a vitamin A-fortified (experimental) or nonfortified (control) group. A 60-g vitamin A-fortified pandesal (containing approximately 133 microg retinol equivalents) or a nonfortified pandesal was consumed by the children 5 d/wk for 30 wk. Vitamin A status, hemoglobin concentration, anthropometric status, morbidity, and dietary intake were assessed at baseline and 30 wk later. A modified relative dose response (MRDR) was assessed in a subsample of 20% of the children ( approximately 75/group) with the lowest initial serum retinol concentration at the 30-wk follow-up. RESULTS: Baseline serum retinol significantly modified the effect of the intervention. The fortified group, whose initial serum retinol concentrations were below the median, had a 0.07 +/- 0.03-micromol/L greater improvement in serum retinol at the 30-wk follow-up than did the control group (P: = 0.02). Improved vitamin A status was also evident in the MRDR subsample. End-of-study differences in the MRDR showed that vitamin A- fortified pandesal intake decreased the percentage of children with inadequate liver vitamin A stores by 50% (15.3% compared with 28.6%; P: = 0.05). CONCLUSIONS: Daily consumption of vitamin A-fortified pandesal significantly improved the vitamin A status of Filipino school-age children with marginal-to-low initial serum retinol concentrations.

Errors, gaps, and misconceptions in the disease-related knowledge of cystic fibrosis patients and their families.

A cross-sectional survey was conducted among 60 families with a child with cystic fibrosis to assess their medical knowledge of the illness. A 63-item, multiple-choice test with acceptable psychometric properties was administered to 60 mothers, 54 fathers, 29 siblings (aged 10 to 23 years), and 18 patients (aged 9 to 22 years). Parents and patients correctly answered approximately three quarters and siblings two thirds of all items. Family members were most knowledgeable about general cystic fibrosis facts, physiotherapy, gastrointestinal symptomatology and treatment, and anatomy. They were less well-informed about respiratory symptomatology and treatment and nutrition. Parental knowledge of genetics and reproductive risks was mediocre, and that of patients and siblings was poor. Knowledge of terminology was uniformly low. Social class was a significant predictor of parental knowledge. If left uncorrected the misconceptions, gaps, and errors in family members' knowledge of cystic fibrosis identified in this study could result in inadverent noncompliance in treatment of the patient.

Global and specific disease-related information needs of cystic fibrosis patients and their families.

A cross-sectional survey of 60 families with a child with cystic fibrosis was undertaken to assess how much family members wanted to be told about the illness, to determine specific information needs concerning selected medical and psychosocial topics, and to determine whether this information had been provided in the past. Self-administered index measures were designed for this purpose. Most family members wanted complete and comprehensive information about cystic fibrosis. A minority of family members claimed they had not received basic medical information. Fathers and siblings wanted more medical information than mothers and patients. The majority of parents and patients wanted a great deal more information on the possible effects of cystic fibrosis on the patient's career, social life, marriage, and reproductive capacity. In general, family members had been given more medical than psychosocial information. Index measures were independent of the effects of patients' age, Shwachman score, and period since diagnosis. Social class was significantly associated with fathers' index measures of their specific information needs and information not given previously.