Multiwavelength Light Curves of Two Remarkable Sagittarius A* Flares.

Sgr A*, the supermassive black hole (SMBH) at the center of our Milky Way Galaxy, is known to be a variable source of X-ray, near-infrared (NIR), and submillimeter radiation and therefore a prime candidate to study the electromagnetic radiation generated by mass accretion flow onto a black hole and/or a related jet. Disentangling the power source and emission mechanisms of this variability is a central challenge to our understanding of accretion flows around SMBHs. Simultaneous multiwavelength observations of the flux variations and their time correlations can play an important role in obtaining a better understanding of possible emission mechanisms and their origin. This paper presents observations of two flares that both apparently violate the previously established patterns in the relative timing of submillimeter/NIR/X-ray flares from Sgr A*. One of these events provides the first evidence of coeval structure between NIR and submillimeter flux increases, while the second event is the first example of the sequence of submillimeter/X-ray/NIR flux increases all occurring within ~1 hr. Each of these two events appears to upend assumptions that have been the basis of some analytic models of flaring in Sgr A*. However, it cannot be ruled out that these events, even though unusual, were just coincidental. These observations demonstrate that we do not fully understand the origin of the multiwavelength variability of Sgr A* and show that there is a continued and important need for long-term, coordinated, and precise multiwavelength observations of Sgr A* to characterize the full range of variability behavior.

Author Correction: A massive core for a cluster of galaxies at a redshift of 4.3.

Change history: In this Letter, the Acknowledgements section should have included the following sentence: "The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.". This omission has been corrected online.

A massive core for a cluster of galaxies at a redshift of 4.3.

Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs1-3. The high-redshift progenitors of these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter4-6. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts 7 . However, recent detections of possible protoclusters hosting such starbursts8-11 do not support the kind of rapid cluster-core formation expected from simulations 12 : the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.

Variability Timescale and Spectral Index of Sgr A* in the Near Infrared: Approximate Bayesian Computation Analysis of the Variability of the Closest Supermassive Black Hole.

Sagittarius A* (Sgr A*) is the variable radio, near-infrared (NIR), and X-ray source associated with accretion onto the Galactic center black hole. We present an analysis of the most comprehensive NIR variability data set of Sgr A* to date: eight 24 hr epochs of continuous monitoring of Sgr A* at 4.5 µm with the IRAC instrument on the Spitzer Space Telescope, 93 epochs of 2.18 µm data from Naos Conica at the Very Large Telescope, and 30 epochs of 2.12 µm data from the NIRC2 camera at the Keck Observatory, in total 94,929 measurements. A new approximate Bayesian computation method for fitting the first-order structure function extracts information beyond current fast Fourier transformation (FFT) methods of power spectral density (PSD) estimation. With a combined fit of the data of all three observatories, the characteristic coherence timescale of Sgr A* is τ b = 243 - 57 + 82 minutes (90% credible interval). The PSD has no detectable features on timescales down to 8.5 minutes (95% credible level), which is the ISCO orbital frequency for a dimensionless spin parameter a = 0.92. One light curve measured simultaneously at 2.12 and 4.5 µm during a low flux-density phase gave a spectral index α s = 1.6 ± 0.1 ( F ν ∝ ν - α s ) . This value implies that the Sgr A* NIR color becomes bluer during higher flux-density phases. The probability densities of flux densities of the combined data sets are best fit by log-normal distributions. Based on these distributions, the Sgr A* spectral energy distribution is consistent with synchrotron radiation from a non-thermal electron population from below 20 GHz through the NIR.

Galaxy growth in a massive halo in the first billion years of cosmic history.

According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far. Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey. High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe. These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch.

Use of computed tomography abdomen and pelvis for investigation of febrile neutropenia in adult haematology patients.

We retrospectively evaluated the use of computed tomography abdomen and pelvis (CTAP) in febrile neutropenic autologous stem cell transplant (ASCT) and acute myeloid leukaemia (AML) patients. CTAP was more common in ASCT patients (59%) compared with AML (31%; P < 0.001). Although abnormal findings were reported in 51%, only 10% resulted in therapy change (addition of anaerobic antibiotic/bowel rest), which would have otherwise been instituted based on clinical grounds. CTAP in these patients rarely provide useful information unsuspected clinically.

A galaxy rapidly forming stars 700 million years after the Big Bang at redshift 7.51.

Of several dozen galaxies observed spectroscopically that are candidates for having a redshift (z) in excess of seven, only five have had their redshifts confirmed via Lyman α emission, at z = 7.008, 7.045, 7.109, 7.213 and 7.215 (refs 1-4). The small fraction of confirmed galaxies may indicate that the neutral fraction in the intergalactic medium rises quickly at z > 6.5, given that Lyman α is resonantly scattered by neutral gas. The small samples and limited depth of previous observations, however, makes these conclusions tentative. Here we report a deep near-infrared spectroscopic survey of 43 photometrically-selected galaxies with z > 6.5. We detect a near-infrared emission line from only a single galaxy, confirming that some process is making Lyman α difficult to detect. The detected emission line at a wavelength of 1.0343 micrometres is likely to be Lyman α emission, placing this galaxy at a redshift z = 7.51, an epoch 700 million years after the Big Bang. This galaxy's colours are consistent with significant metal content, implying that galaxies become enriched rapidly. We calculate a surprisingly high star-formation rate of about 330 solar masses per year, which is more than a factor of 100 greater than that seen in the Milky Way. Such a galaxy is unexpected in a survey of our size, suggesting that the early Universe may harbour a larger number of intense sites of star formation than expected.

Dusty starburst galaxies in the early Universe as revealed by gravitational lensing.

In the past decade, our understanding of galaxy evolution has been revolutionized by the discovery that luminous, dusty starburst galaxies were 1,000 times more abundant in the early Universe than at present. It has, however, been difficult to measure the complete redshift distribution of these objects, especially at the highest redshifts (z > 4). Here we report a redshift survey at a wavelength of three millimetres, targeting carbon monoxide line emission from the star-forming molecular gas in the direction of extraordinarily bright millimetre-wave-selected sources. High-resolution imaging demonstrates that these sources are strongly gravitationally lensed by foreground galaxies. We detect spectral lines in 23 out of 26 sources and multiple lines in 12 of those 23 sources, from which we obtain robust, unambiguous redshifts. At least 10 of the sources are found to lie at z > 4, indicating that the fraction of dusty starburst galaxies at high redshifts is greater than previously thought. Models of lens geometries in the sample indicate that the background objects are ultra-luminous infrared galaxies, powered by extreme bursts of star formation.

A massive, cooling-flow-induced starburst in the core of a luminous cluster of galaxies.

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.

Palliative care, double effect and the law in Australia.

Care and decision-making at the end of life that promotes comfort and dignity is widely endorsed by public policy and the law. In ethical analysis of palliative care interventions that are argued potentially to hasten death, these may be deemed to be ethically permissible by the application of the doctrine of double effect, if the doctor's intention is to relieve pain and not cause death. In part because of the significance of ethics in the development of law in the medical sphere, this doctrine is also likely to be recognized as part of Australia's common law, although hitherto there have been no cases concerning palliative care brought before a court in Australia to test this. Three Australian States have, nonetheless, created legislative defences that are different from the common law with the intent of clarifying the law, promoting palliative care, and distinguishing it from euthanasia. However, these defences have the potential to provide less protection for doctors administering palliative care. In addition to requiring a doctor to have an appropriate intent, the defences insist on adherence to particular medical practice standards and perhaps require patient consent. Doctors providing end-of-life care in these States need to be aware of these legislative changes. Acting in accordance with the common law doctrine of double effect may not provide legal protection. Similar changes are likely to occur in other States and Territories as there is a trend towards enacting legislative defences that deal with the provision of palliative care.

Intranasal sufentanil for cancer-associated breakthrough pain.

The objective of this study was to demonstrate the efficacy, safety and patient acceptability of the use of intranasal sufentanil for cancer-associated breakthrough pain. This was a prospective, open label, observational study of patients in three inpatient palliative care units in Australia. Patients on opioids with cancer-associated breakthrough pain and clinical evidence of opioid responsiveness to their breakthrough pain were given intranasal (IN) Sufentanil via a GO Medical patient controlled IN analgesia device. The main outcome measures were pain scores, need to revert to previous breakthrough opioid after 30 min, number of patients who chose to continue using IN sufentanil, and adverse effects. There were 64 episodes of use of IN sufentanil for breakthrough pain in 30 patients. There was a significant reduction in pain scores at 15 (P < 0.0001) and 30 min (P < 0.0001). In only 4/64 (6%) episodes of breakthrough pain did the participants choose to revert to their prestudy breakthrough medication. Twenty-three patients (77%) rated IN sufentanil as better than their prestudy breakthrough medication. The incidence of adverse effects was low and most were mild. Our study showed that IN sufentanil can provide relatively rapid onset, intense but relatively short lasting analgesia and in the palliative care setting it is an effective, practical, and safe option for breakthrough pain.

The extreme Kuiper Belt binary 2001 QW322.

The study of binary Kuiper Belt objects helps to probe the dynamic conditions present during planet formation in the solar system. We report on the mutual-orbit determination of 2001 QW322, a Kuiper Belt binary with a very large separation whose properties challenge binary-formation and -evolution theories. Six years of tracking indicate that the binary's mutual-orbit period is approximately 25 to 30 years, that the orbit pole is retrograde and inclined 50 degrees to 62 degrees from the ecliptic plane, and, most surprisingly, that the mutual orbital eccentricity is <0.4. The semimajor axis of 105,000 to 135,000 kilometers is 10 times that of other near-equal-mass binaries. Because this weakly bound binary is prone to orbital disruption by interlopers, its lifetime in its present state is probably less than 1 billion years.

Inorganic chemistry of defensive peroxidases in the human oral cavity.

The innate host response system is comprised of various mechanisms for orchestrating host response to microbial infection of the oral cavity. The heterogeneity of the oral cavity and the associated microenvironments that are produced give rise to different chemistries that affect the innate defense system. One focus of this review is on how these spatial differences influence the two major defensive peroxidases of the oral cavity, salivary peroxidase (SPO) and myeloperoxidase (MPO). With hydrogen peroxide (H(2)O(2)) as an oxidant, the defensive peroxidases use inorganic ions to produce antimicrobials that are generally more effective than H(2)O(2) itself. The concentrations of the inorganic substrates are different in saliva vs. gingival crevicular fluid (GCF). Thus, in the supragingival regime, SPO and MPO work in unison for the exclusive production of hypothiocyanite (OSCN(-), a reactive inorganic species), which constantly bathes nascent plaques. In contrast, MPO is introduced to the GCF during inflammatory response, and in that environment it is capable of producing hypochlorite (OCl(-)), a chemically more powerful oxidant that is implicated in host tissue damage. A second focus of this review is on inter-person variation that may contribute to different peroxidase function. Many of these differences are attributed to dietary or smoking practices that alter the concentrations of relevant inorganic species in the oral cavity (e.g.: fluoride, F(-); cyanide, CN(-); cyanate, OCN(-); thiocyanate, SCN(-); and nitrate, NO(3)(-)). Because of the complexity of the host and microflora biology and the associated chemistry, it is difficult to establish the significance of the human peroxidase systems during the pathogenesis of oral diseases. The problem is particularly complex with respect to the gingival sulcus and periodontal pockets (where the very different defensive stratagems of GCF and saliva co-mingle). Despite this complexity, intriguing in vitro and in vivo studies are reviewed here that reveal the interplay between peroxidase function and associated inorganic chemistry.

The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome.

Metazoan genomes contain large numbers of genes that participate in responses to environmental stressors. We surveyed the sea urchin Strongylocentrotus purpuratus genome for homologs of gene families thought to protect against chemical stressors; these genes collectively comprise the 'chemical defensome.' Chemical defense genes include cytochromes P450 and other oxidases, various conjugating enzymes, ATP-dependent efflux transporters, oxidative detoxification proteins, and transcription factors that regulate these genes. Together such genes account for more than 400 genes in the sea urchin genome. The transcription factors include homologs of the aryl hydrocarbon receptor, hypoxia-inducible factor, nuclear factor erythroid-derived 2, heat shock factor, and nuclear hormone receptors, which regulate stress-response genes in vertebrates. Some defense gene families, including the ABCC, the UGT, and the CYP families, have undergone expansion in the urchin relative to other deuterostome genomes, whereas the stress sensor gene families do not show such expansion. More than half of the defense genes are expressed during embryonic or larval life stages, indicating their importance during development. This genome-wide survey of chemical defense genes in the sea urchin reveals evolutionary conservation of this network combined with lineage-specific diversification that together suggest the importance of these chemical stress sensing and response mechanisms in early deuterostomes. These results should facilitate future studies on the evolution of chemical defense gene networks and the role of these networks in protecting embryos from chemical stress during development.

Prolactin delays hair regrowth in mice.

Mammalian hair growth is cyclic, with hair-producing follicles alternating between active (anagen) and quiescent (telogen) phases. The timing of hair cycles is advanced in prolactin receptor (PRLR) knockout mice, suggesting that prolactin has a role in regulating follicle cycling. In this study, the relationship between profiles of circulating prolactin and the first post-natal hair growth cycle was examined in female Balb/c mice. Prolactin was found to increase at 3 weeks of age, prior to the onset of anagen 1 week later. Expression of PRLR mRNA in skin increased fourfold during early anagen. This was followed by upregulation of prolactin mRNA, also expressed in the skin. Pharmacological suppression of pituitary prolactin advanced dorsal hair growth by 3.5 days. Normal hair cycling was restored by replacement with exogenous prolactin for 3 days. Increasing the duration of prolactin treatment further retarded entry into anagen. However, prolactin treatments, which began after follicles had entered anagen at 26 days of age, did not alter the subsequent progression of the hair cycle. Skin from PRLR-deficient mice grafted onto endocrine-normal hosts underwent more rapid hair cycling than comparable wild-type grafts, with reduced duration of the telogen phase. These experiments demonstrate that prolactin regulates the timing of hair growth cycles in mice via a direct effect on the skin, rather than solely via the modulation of other endocrine factors.

An almost head-on collision as the origin of two off-centre rings in the Andromeda galaxy.

The unusual morphology of the Andromeda galaxy (Messier 31, the closest spiral galaxy to the Milky Way) has long been an enigma. Although regarded for decades as showing little evidence of a violent history, M31 has a well-known outer ring of star formation at a radius of ten kiloparsecs whose centre is offset from the galaxy nucleus. In addition, the outer galaxy disk is warped, as seen at both optical and radio wavelengths. The halo contains numerous loops and ripples. Here we report the presence of a second, inner dust ring with projected dimensions of 1.5 x 1 kiloparsecs and offset by about half a kiloparsec from the centre of the galaxy (based upon an analysis of previously-obtained data). The two rings appear to be density waves propagating in the disk. Numerical simulations indicate that both rings result from a companion galaxy plunging through the centre of the disk of M31. The most likely interloper is M32. Head-on collisions between galaxies are rare, but it appears nonetheless that one took place 210 million years ago in our Local Group of galaxies.

The properties of foams and lattices.

Man and nature both exploit the remarkable properties of cellular solids, by which we mean foams, meshes and microlattices. To the non-scientist, their image is that of soft, compliant, things: cushions, packaging and padding. To the food scientist they are familiar as bread, cake and desserts of the best kind: meringue, mousse and sponge. To those who study nature they are the structural materials of their subject: wood, coral, cancellous bone. And to the engineer they are of vast importance in building lightweight structures, for energy management, for thermal insulation, filtration and much more. When a solid is converted into a material with a foam-like structure, the single-valued properties of the solid are extended. By properties we mean stiffness, strength, thermal conductivity and diffusivity, electrical resistivity and so forth. And the extension is vast-the properties can be changed by a factor of 1000 or more. Perhaps the most important concept in analysing the mechanical behaviour is that of the distinction between a stretch- and a bending-dominated structure. The first is exceptionally stiff and strong for a given mass; the second is compliant and, although not strong, it absorbs energy well when compressed. This paper summarizes a little of the way in which the mechanical properties of cellular solids are analysed and illustrates the range of properties offered by alternative configurations.

Prospective audit of short-term concurrent ketamine, opioid and anti-inflammatory ('triple-agent') therapy for episodes of acute on chronic pain.

AIM: This prospective audit was undertaken in order to document the analgesic response and adverse effects of concurrent short-term ('burst') triple-agent analgesic (ketamine, an opioid and an anti-inflammatory agent--either steroidal or non-steroidal) administration, for episodes of acute on chronic pain. The clinical hypothesis in this study is that better pain control may be obtained by simultaneous multiple target receptor blockade. METHOD: The response of 18 patients is reported. The pain and analgesic requirement data for the 24 h before starting triple-agent therapy were compared with the last 24 h on the triple-agent therapy. Patients were then classified as responders or non-responders. RESULTS: According to stringent clinical criteria, 12 out of the 18 patients were classified as responders. The response rate was highest for somatic pain (7/9) and appeared to decrease with duration of prior uncontrolled pain. Only four out of the 18 patients reported adverse effects and all of these were minor. CONCLUSIONS: The results suggest that this 'burst' triple-agent approach is safe and effective in an inpatient palliative care population during episodes of poorly controlled acute on chronic pain, and warrants further investigation to ascertain whether it gives superior results compared to the 'gold-standard' WHO ladder approach.

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.