Needle-like structures discovered on positively charged lightning branches.

Lightning is a dangerous yet poorly understood natural phenomenon. Lightning forms a network of plasma channels propagating away from the initiation point with both positively and negatively charged ends-called positive and negative leaders1. Negative leaders propagate in discrete steps, emitting copious radio pulses in the 30-300-megahertz frequency band2-8 that can be remotely sensed and imaged with high spatial and temporal resolution9-11. Positive leaders propagate more continuously and thus emit very little high-frequency radiation12. Radio emission from positive leaders has nevertheless been mapped13-15, and exhibits a pattern that is different from that of negative leaders11-13,16,17. Furthermore, it has been inferred that positive leaders can become transiently disconnected from negative leaders9,12,16,18-20, which may lead to current pulses that both reconnect positive leaders to negative leaders11,16,17,20-22 and cause multiple cloud-to-ground lightning events1. The disconnection process is thought to be due to negative differential resistance18, but this does not explain why the disconnections form primarily on positive leaders22, or why the current in cloud-to-ground lightning never goes to zero23. Indeed, it is still not understood how positive leaders emit radio-frequency radiation or why they behave differently from negative leaders. Here we report three-dimensional radio interferometric observations of lightning over the Netherlands with unprecedented spatiotemporal resolution. We find small plasma structures-which we call 'needles'-that are the dominant source of radio emission from the positive leaders. These structures appear to drain charge from the leader, and are probably the reason why positive leaders disconnect from negative ones, and why cloud-to-ground lightning connects to the ground multiple times.

A large light-mass component of cosmic rays at 10(17)-10(17.5) electronvolts from radio observations.

Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10(17)-10(18) electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal comes from accelerators capable of producing cosmic rays of these energies. Cosmic rays initiate air showers--cascades of secondary particles in the atmosphere-and their masses can be inferred from measurements of the atmospheric depth of the shower maximum (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground. Current measurements have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays is a rapidly developing technique for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10(17)-10(17.5) electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10(17.5) electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10(17)-10(17.5) electronvolt range.

Whole genome sequencing improved case ascertainment in an outbreak of Shiga toxin-producing Escherichia coli O157 associated with raw drinking milk.

Five cases of STEC O157 phage type (PT) 21/28 reported consumption of raw cows' drinking milk (RDM) produced at a dairy farm in the South West of England. STEC O157 PT21/28 was isolated from faecal specimens from milking cows on the implicated farm. Whole genome sequencing (WGS) showed that human and cattle isolates were the same strain. Further analysis of WGS data confirmed that sequences of isolates from an additional four cases (who did not report consumption of RDM when first questioned) fell within the same five single nucleotide polymorphism cluster as the initial five cases epidemiologically linked to the consumption of RDM. These four additional cases identified by WGS were investigated further and were, ultimately, associated with the implicated farm. The RDM outbreak strain encoded stx2a, which is associated with increased pathogenicity and severity of symptoms. Further epidemiological analysis showed that 70% of isolates within a wider cluster containing the outbreak strain were from cases residing in, or linked to, the same geographical region of England. During this RDM outbreak, use of WGS improved case ascertainment and provided insights into the evolution of a highly pathogenic clade of STEC O157 PT21/28 stx2a associated with the South West of England.

Probing Atmospheric Electric Fields in Thunderstorms through Radio Emission from Cosmic-Ray-Induced Air Showers.

We present measurements of radio emission from cosmic ray air showers that took place during thunderstorms. The intensity and polarization patterns of these air showers are radically different from those measured during fair-weather conditions. With the use of a simple two-layer model for the atmospheric electric field, these patterns can be well reproduced by state-of-the-art simulation codes. This in turn provides a novel way to study atmospheric electric fields.

Detection and imaging of atmospheric radio flashes from cosmic ray air showers.

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.

What is associated with being active in arthritis? Analysis from the Obstacles to Action study.

BACKGROUND: Many adults with arthritis do not achieve physical activity levels recommended for good health. This study aimed to identify factors associated with physical activity participation in people with arthritis. METHODS: 1106 out of 8163 adults with self-reported arthritis were identified from the 2003 Obstacles to Action study. Participants were classified as active if they reported 30 min of moderate activity > or = 5 days a week or 20 min of vigorous activity > or = 3 days a week (n = 613), or insufficiently active if they did not (n = 438). Sociodemographic factors, attitudes, self-efficacy, motivators and barriers to being active were analysed. RESULTS: Active people with arthritis had a lower burden of chronic disease than insufficiently active people (18% with three or more chronic medical conditions vs 33%, P < 0.0001). Active participants believed more strongly in the benefits of physical activity, reported higher levels of encouragement from others and had greater overall levels of self-efficacy when compared with the less active participants (P for all <0.0001). Arthritis, fatigue and discomfort were ranked by both groups as the top three barriers. However, the active participants reported lower impact scores for these barriers than the inactive group (P for all <0.0001). These findings persisted after adjusting for occupational status, body mass index and comorbidities. CONCLUSION: Active adults with arthritis have lower levels of chronic disease, greater self-efficacy and fewer psychosocial barriers. Recognition of such barriers and motivators may be useful when designing intervention programmes to help people with arthritis initiate or intensify physical activity participation.

ZD1542, a potent thromboxane A2 synthase inhibitor and receptor antagonist in vitro.

1. The thromboxane A2 synthase (TXS) inhibitory activity and the thromboxane A2 (TP)-receptor blocking action of ZD1542 (4(Z)-6-[2S,4S,5R)-2-[1-methyl-1-(2-nitro-4-tolyloxy)ethyl]-4-(3- pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been evaluated in vitro on platelets and whole blood from a range of species including man. Antagonist activity has also been investigated in vascular and pulmonary smooth muscle preparations in vitro. 2. ZD1542 caused concentration-dependent inhibition of human platelet microsomal thromboxane B2 (TXB2) production in vitro (IC50 = 0.016 microM); this inhibition was associated with an increase in prostaglandin E2 (PGE2) and PGF2 alpha formation. 3. ZD1542 also inhibited collagen-stimulated TXS in human, rat and dog whole blood giving IC50 values of 0.018, 0.009 and 0.049 microM respectively. The drug did not modify platelet cyclo-oxygenase activity as inhibition of TXB2 formation was associated with a concomitant increase in the levels of PGD2, PGE2 and PGF2 alpha. ZD1542 had little if any effect against cultured human umbilical vein endothelial cell (HUVEC) cyclo-oxygenase (IC50 > 100 microM) and prostacyclin (PGI2) synthase (IC50 = 18.0 +/- 8.6 microM). 4. ZD1542 caused concentration-dependent inhibition of U46619-induced aggregation responses of human, rat and dog platelets yielding apparent pA2 values of 8.3, 8.5 and 9.1 respectively. The drug was selective as, at concentrations up to 100 microM, it did not modify 5-hydroxytryptamine (5-HT) or the primary phases of adenosine diphosphate (ADP) and adrenaline-induced aggregation. Furthermore, ZD1542 (100 microM) modified only weakly the platelet effects of PGD2, PGE1 and PGI2. 5. ZD1542 also caused concentration-dependent inhibition of U46619-mediated contractions of rat thoracic aorta, guinea-pig trachea and lung parenchyma preparations giving apparent pA2 values of 8.6,8.3 and 8.5 respectively. At concentrations approaching three orders of magnitude greater than those required to block U46619-mediated contractions, the drug did not affect the actions of non-prostanoid agonists or exhibit agonist activity in any of the smooth muscle preparations employed; neither did it interact at EP- or FP-receptors.6. In conclusion, the present study demonstrates that ZD1542 is a drug that exhibits both potent,selective TXS inhibition and TXA2 receptor antagonism.

ZD9583, an orally effective thromboxane A2 synthase inhibitor and receptor antagonist with a sustained duration of action in rat and dog.

The thromboxane A2 (TXA2) synthase inhibitory activity and the TXA2 receptor (TP-receptor) blocking action of ZD9583 ((4Z)-6-[(2S,4S,5R)-2-(1-[2-cyano-4-methylphenoxy]-1-methylethyl) -4-(3-pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been evaluated in-vitro by use of whole blood and platelets from man, and ex-vivo by use of platelets and whole blood from rats and dogs. ZD9583 caused concentration-dependent inhibition of human platelet microsomal TXA2 production with an IC50 of 0.017 +/- 0.003 microM; this inhibition was associated with an increase in prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) formation. ZD9583 also inhibited collagen-stimulated TXA2 synthesis in whole blood from man, rat and dog giving IC50 values of 0.027 +/- 0.005, 0.02 +/- 0.006 and 0.013 +/- 0.01 microM, respectively. The drug did not modify platelet cyclooxygenase activity as inhibition of thromboxane B2 (TXB2) formation was associated with a concomitant increased synthesis of prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. ZD9583 had little effect on cultured human umbilical vein endothelial cell prostacyclin synthase giving an IC50 of 24.2 +/- 4.9 microM. In-vitro ZD9583 caused concentration-dependent inhibition of U46619-induced aggregation responses of platelets from man, rat and dog, yielding apparent log A2 values of 8.7 +/- 0.12, 8.8 +/- 0.2 and 9.3 +/- 0.2, respectively. The drug was selective; at concentrations up to 100 microM it did not affect 5-hydroxytryptamine or the primary phases of adenosine diphosphate and adrenaline-induced aggregation. ZD9583 (100 microM) did not, furthermore, modify the platelet inhibitory effects of PGD2, prostaglandin E1 (PGE1) and prostacyclin. Oral administration of ZD9583 (3-10 mg kg-1) to both rats and dogs caused dose-dependant inhibition of collagen-stimulated TXA2 production ex-vivo which persisted for up to 12 h. The drug also caused profound TXA2 receptor blockade in both species for in excess of 12-h after an oral dose of 3 mg kg-1. ZD9583 (3 mg kg-1, p.o.), when administered to dogs over a five-day period at 12 h intervals, did not cause either tachyphylaxis or an accumulation of effect. We conclude that ZD9583 is a potent, selective, orally active thromboxane synthase inhibitor and TXA2 receptor antagonist.

The experience of caring for a family member with Alzheimer's disease.

The purpose of this phenomenological study was to describe the experience of caring for a family member with Alzheimer's disease or related disorder (ADRD) living at home among a diverse sample of 103 family caregivers. The study involved secondary analysis of in-depth transcribed interview data using van Kaam's rigorous four phase, 12-step psychophenomenological method. A total of 2,115 descriptive expressions were categorized into 38 preliminary structural elements. Eight essential structural elements emerged from an analysis of the preliminary structural elements. The eight elements were then synthesized to form the following synthetic structural definition: Caring for a family member living at home with ADRD was experienced as "being immersed in caregiving; enduring stress and frustration; suffering through the losses; integrating ADRD into our lives and preserving integrity; gathering support; moving with continuous change; and finding meaning and joy."

The overview effect: the impact of space exploration on the evolution of nursing science.

The purpose of this article is to explore the overview effect, an experience evoked by space travel that has the capacity to transform all patterns of human existence and evolution toward greater potentials in human diversity and creativity. As nurses migrate with humanity into the solar system and beyond, they will experience the overview effect. The core components of the effect include changed perceptions of space, time, sound, and weight which have the potential to transform the evolution of nursing science. Nursing paradigms will encompass a view of humanity as integral with an infinite evolutionary universe. After generations of living in space in a diversity of new environments, the physical body will undergo radical changes, and the meaning of health will be transformed. The article concludes with a discussion on the parallels between Rogers' science of unitary human beings and the overview effect.

Alternative approaches to nursing practice: application of Peplau, Rogers, and Parse.

This article demonstrates three major nursing theories in practice. The uniqueness of each theory is clarified through the presentation of nursing formulations and practice implications. The discussion provides a metaperspective of how practice based in nursing theory is different from traditional practice and how nursing theory can guide practice.

Synchronous x-ray and radio mode switches: a rapid global transformation of the pulsar magnetosphere.

Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.