Sniffing and Peeking at Mars


The ExoMars Trace Gas Orbiter gets into position and takes some new pictures

Sniffing and Peeking at Mars

Although it arrived at Mars back in October 2016, the ESA/Roscosmos mission called ExoMars Trace Gas Orbiter (and no, I couldn’t see a nice acronym in there either) has spent the last 11 months getting into a working orbit.

Using aerobraking the spacecraft has shrunk its highly elliptical capture orbit to a relatively tight, near circular path around Mars, about 400 km above the surface. This is the prime science mission configuration. Although the highest profile science goal for the orbiter is arguably its study of gases like methane in the martian atmosphere, it’s got some other nifty science instruments on board.

One of those is the CaSSIS camera – capable of taking stereoscopic images of the planetary surface to a resolution of some 4.5 meters. Developed at the University of Bern in Switzerland, CaSSIS has been returning data since reaching Mars, but in the new orbit these pictures are taking on a new level of detail. Using a set of 3 color filters – skewed towards the red and infrared bands the following image shows a 40 km long stretch of Korolev Crater at high northern latitudes. Bright looking material is ice.

Credit: ESA, Roscosmos and CaSSIS

With a close up of one area shown here:

Credit: ESA, Roscosmos and CaSSIS

Images like these will help add to our increasingly detailed maps of Mars. In many respects this alien surface is already better mapped out than the Earth’s ocean floors. The CaSSIS data will also help improve our understanding of the comings and goings of volatiles like water and carbon dioxide on Mars, linking these data with the spectroscopic study of trace gases.

Is, for example, methane on Mars coming from specific locations? And is there evidence that it could have a biological origin?

These are big questions, and as ExoMars goes about its business we’re going to get closer to some answers.

 

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URL: http://www.romancewithbooks.com

Gravitational Wave Kicks Monster Black Hole Out Of Galactic Core


Gravitational Wave Kicks Monster Black Hole Out Of Galactic Core

Gravitational Wave Kicks Monster Black Hole Out Of Galactic Core
Runaway black hole is the most massive ever detected far from its central home
Normally, hefty black holes anchor the centers of galaxies. So researchers were surprised to discover a supermassive black hole speeding through the galactic suburbs. Black holes cannot be observed directly, but they are the energy source at the heart of quasars — intense, compact gushers of radiation that can outshine an entire galaxy. NASA’s Hubble Space Telescope made the discovery by finding a bright quasar located far from the center of the host galaxy.Researchers estimate that it took the equivalent energy of 100 million supernovas exploding simultaneously to jettison the black hole. What could pry this giant monster from its central home? The most plausible explanation for this propulsive energy is that the monster object was given a kick by gravitational waves unleashed by the merger of two black holes as a result of a collision between two galaxies. First predicted by Albert Einstein, gravitational waves are ripples in the fabric of space that are created when two massive objects collide.

Astronomers have uncovered a supermassive black hole that has been propelled out of the center of a distant galaxy by what could be the awesome power of gravitational waves.

Though there have been several other suspected, similarly booted black holes elsewhere, none has been confirmed so far. Astronomers think this object, detected by NASA’s Hubble Space Telescope, is a very strong case. Weighing more than 1 billion suns, the rogue black hole is the most massive black hole ever detected to have been kicked out of its central home.

Researchers estimate that it took the equivalent energy of 100 million supernovas exploding simultaneously to jettison the black hole. The most plausible explanation for this propulsive energy is that the monster object was given a kick by gravitational waves unleashed by the merger of two hefty black holes at the center of the host galaxy.

First predicted by Albert Einstein, gravitational waves are ripples in space that are created when two massive objects collide. The ripples are similar to the concentric circles produced when a hefty rock is thrown into a pond. Last year, the Laser Interferometer Gravitational-Wave Observatory (LIGO) helped astronomers prove that gravitational waves exist by detecting them emanating from the union of two stellar-mass black holes, which are several times more massive than the sun.

Hubble’s observations of the wayward black hole surprised the research team. “When I first saw this, I thought we were seeing something very peculiar,” said team leader Marco Chiaberge of the Space Telescope Science Institute (STScI) and Johns Hopkins University, in Baltimore, Maryland. “When we combined observations from Hubble, the Chandra X-ray Observatory, and the Sloan Digital Sky Survey, it all pointed towards the same scenario. The amount of data we collected, from X-rays to ultraviolet to near-infrared light, is definitely larger than for any of the other candidate rogue black holes.”

Chiaberge’s paper will appear in the March 30 issue of Astronomy & Astrophysics.

Hubble images taken in visible and near-infrared light provided the first clue that the galaxy was unusual. The images revealed a bright quasar, the energetic signature of a black hole, residing far from the galactic core. Black holes cannot be observed directly, but they are the energy source at the heart of quasars – intense, compact gushers of radiation that can outshine an entire galaxy. The quasar, named 3C 186, and its host galaxy reside 8 billion light-years away in a galaxy cluster. The team discovered the galaxy’s peculiar features while conducting a Hubble survey of distant galaxies unleashing powerful blasts of radiation in the throes of galaxy mergers.

“I was anticipating seeing a lot of merging galaxies, and I was expecting to see messy host galaxies around the quasars, but I wasn’t really expecting to see a quasar that was clearly offset from the core of a regularly shaped galaxy,” Chiaberge recalled. “Black holes reside in the center of galaxies, so it’s unusual to see a quasar not in the center.”

The team calculated the black hole’s distance from the core by comparing the distribution of starlight in the host galaxy with that of a normal elliptical galaxy from a computer model. The black hole had traveled more than 35,000 light-years from the center, which is more than the distance between the sun and the center of the Milky Way.

Based on spectroscopic observations taken by Hubble and the Sloan survey, the researchers estimated the black hole’s mass and measured the speed of gas trapped near the behemoth object. Spectroscopy divides light into its component colors, which can be used to measure velocities in space. “To our surprise, we discovered that the gas around the black hole was flying away from the galaxy’s center at 4.7 million miles an hour,” said team member Justin Ely of STScI. This measurement is also a gauge of the black hole’s velocity, because the gas is gravitationally locked to the monster object.

The astronomers calculated that the black hole is moving so fast it would travel from Earth to the moon in three minutes. That’s fast enough for the black hole to escape the galaxy in 20 million years and roam through the universe forever.

The Hubble image revealed an interesting clue that helped explain the black hole’s wayward location. The host galaxy has faint arc-shaped features called tidal tails, produced by a gravitational tug between two colliding galaxies. This evidence suggests a possible union between the 3C 186 system and another galaxy, each with central, massive black holes that may have eventually merged.

Based on this visible evidence, along with theoretical work, the researchers developed a scenario to describe how the behemoth black hole could be expelled from its central home. According to their theory, two galaxies merge, and their black holes settle into the center of the newly formed elliptical galaxy. As the black holes whirl around each other, gravity waves are flung out like water from a lawn sprinkler. The hefty objects move closer to each other over time as they radiate away gravitational energy. If the two black holes do not have the same mass and rotation rate, they emit gravitational waves more strongly along one direction. When the two black holes collide, they stop producing gravitational waves. The newly merged black hole then recoils in the opposite direction of the strongest gravitational waves and shoots off like a rocket.

The researchers are lucky to have caught this unique event because not every black-hole merger produces imbalanced gravitational waves that propel a black hole in the opposite direction. “This asymmetry depends on properties such as the mass and the relative orientation of the back holes’ rotation axes before the merger,” said team member Colin Norman of STScI and Johns Hopkins University. “That’s why these objects are so rare.”

An alternative explanation for the offset quasar, although unlikely, proposes that the bright object does not reside within the galaxy. Instead, the quasar is located behind the galaxy, but the Hubble image gives the illusion that it is at the same distance as the galaxy. If this were the case, the researchers should have detected a galaxy in the background hosting the quasar.

If the researchers’ interpretation is correct, the observations may provide strong evidence that supermassive black holes can actually merge. Astronomers have evidence of black-hole collisions for stellar-mass black holes, but the process regulating supermassive black holes is more complex and not completely understood.

The team hopes to use Hubble again, in combination with the Atacama Large Millimeter/submillimeter Array (ALMA) and other facilities, to more accurately measure the speed of the black hole and its gas disk, which may yield more insight into the nature of this bizarre object.

The Hubble Space Telescope is a project of international cooperation between NASA and ESA (European Space Agency). NASA’s Goddard Space Flight Center in Greenbelt, Maryland, manages the telescope. The Space Telescope Science Institute in Baltimore conducts Hubble science operations. STScI is operated for NASA by the Association of Universities for Research in Astronomy, Inc., in Washington, D.C.

Source:http://hubblesite.org

Management of anaemia – Anaemia Management in Chronic Kidney Disease – National Library of Medicine – PubMed Health


5.1. Initiation of ESA therapy in iron-deficient patients

5.1.1. Clinical introduction

Iron management forms an essential part of the treatment of anaemia associated with CKD and availability of iron is of key importance for iron optimal erythropoiesis. Before erythropoietin treatment was available, patients with anaemia associated with CKD frequently received blood transfusions. One of the consequences of this was the progressive accumulation of iron, manifested by extremely high ferritin levels in excess of 1,500 to 5,000 μg/l. With the advent of ESA therapy this accumulated iron was rapidly mobilised, and serum ferritin levels fell accordingly. We now recognise that in order to manage the anaemia optimally, there needs to be an appropriate balance between stimulation of erythropoiesis and provision of iron as a key substrate in the manufacture of haemoglobin.

In health, iron is almost completely recycled and losses are of the order of 1 mg/day, requiring minimal replacement. Iron deficiency is the most common cause of anaemia worldwide. This is due to either negative iron balance through blood loss (commonly gastrointestinal or menstrual), or to inadequate intake (which may be nutritional or related to poor gastrointestinal absorption). Patients with CKD are particularly susceptible to gastrointestinal blood loss and additional sources of significant blood loss include routine (and non-routine) blood sampling, and blood loss on haemodialysis which may represent the need for up to an extra 3,000 mg iron per year. In the first 3 months of ESA therapy it is estimated that a haemodialysis patient needs an extra 1,000 mg of supplemental iron, underlining the importance of adequate availability of iron for optimal erythropoiesis34.

5.1.2. Clinical methodological introduction

A comprehensive literature search did not identify any studies that were suitable to address the clinical aspects of this section, therefore no evidence statements are given.

5.1.3. Health economics methodological introduction

One study met methodological criteria282. This Canadian study estimated annual cost savings of intravenous iron dextran from reductions in EPO and oral iron in patients who did not tolerate or did not respond adequately to oral iron in a 6-month prospective study with an initial goal serum ferritin of 100–200 μg/l. If an increase in haemoglobin was not achieved, transferrin saturation was measured and when less than 20%, the goal serum ferritin was increased to 200–300 μg/l. EPO was used to maintain haemoglobin levels of 9.5–10.5 g/l only if ferritin targets were met282.

5.1.4. Health economic evidence statements

The study found that intravenous iron dextran saved approximately Canadian $63 per patient ($3,016 total) from EPO savings and oral iron savings in 50 patients. However, the initial cost of i.v. iron dextran loading was $3,426 in the first year. Therefore, the loading dose of i.v. iron dextran offset the cost reduction in EPO and oral iron in the first year but would not apply in subsequent years. Intravenous iron dextran costs were $29,692 (Canadian $, 1996) per year in the 50 patients in the study with $30,120 of EPO savings per year and $2,738 from oral iron savings per year282.

5.1.5. From evidence to recommendations

There is little evidence in this area but the GDG agreed that ESAs alone should not be administered to patients with iron deficiency (ferritin level <100 μg/l). The GDG debated whether ESAs should be administered together with iron supplements. It was noted that some patients with higher GFR had a good response to iron treatment alone but that there was no evidence to support a threshold for iron stores required prior to commencing ESAs, except in patients with iron deficiency.

5.1.6. Recommendations

7.

ESA therapy should not be initiated in the presence of absolute iron deficiency without also managing the iron deficiency. [D(GPP)]

8.

In people with functional iron deficiency, iron supplements should be given concurrently when initiating ESA therapy.[D(GPP)]

Also see recommendation 42 in section 6.12.6.

5.2. Maximum iron levels in patients with anaemia of CKD

5.2.1. Clinical introduction

Iron is crucial for survival and is necessary for erythropoiesis and the production of usable energy through oxidative phosphorylation. However, iron-overload states are harmful and the potent oxidising ability of non-transferrin bound iron makes it potentially toxic. The majority of iron not actively circulating as haemoglobin is safely sequestered in the form of ferritin and hemosiderin in macrophages of the reticuloendothelial system. Molecules that hold iron tend to be very large, containing a central core of iron with a proteinaceous envelope that insulates the body from the iron atom. We know that in iron-overload states, such as haemochromatosis, in which serum ferritin levels can increase to more than 10,000 μg/l, the body is presented with unmanageable levels of free iron leading to iron-related toxicity. The focus of debate about potential iron toxicity in patients with anaemia associated with CKD revolves around the possible increased susceptibility to infectious complications and increased cardiovascular morbidity and mortality engendered by iron administration. In vitro, iron preparations enhance bacterial growth, induce leukocyte dysfunction, inhibit phagocytosis, produce reactive oxygen species, increase oxidative stress, consume antioxidants and, at very high doses, promote lipid peroxidation and cell death. These observations have led to concern that too much iron might translate these in vitro phenomena into adverse infectious and cardiovascular in vivo effects.

5.2.2. Methodological introduction

A comprehensive literature search did not identify any studies that were suitable to address the clinical or economic aspects of this section, therefore no evidence statements are given.

5.2.3. From evidence to recommendations

Because of the lack of evidence, it was agreed that an upper limit of 800 μg/l of ferritin should be used in line with the current European Best Practice Guidelinesa. This level is drawn from data on iron toxicity studies performed in the pre-ESA era that demonstrated that high ferritin levels >1,000 μg/l led to the deposition of iron in tissues. However, in practice, in order to prevent serum ferritin from rising above 800 μg/l a patient’s iron dose should be reviewed if their serum ferritin levels exceed 500 μg/l. It was noted that it was not known whether there are any long-term consequences related to the administration of intravenous iron as this route bypassed normal absorption routes and homeostatic mechanisms.

It should be noted that ferritin is an acute phase protein that is increased during inflammatory events, this affects the interpretation of some of the studies reviewed.

5.2.4. Recommendation

9.

In people treated with iron, serum ferritin levels should not rise above 800 μg/l. In order to prevent this, the dose of iron should be reviewed when serum ferritin levels reach 500 μg/l. [D (GPP)]

5.3. Clinical utility of ESA therapy in iron-replete patients

5.3.1. Clinical introduction

Patients who are iron replete (ferritin >100 μg/l and %HRC <6% or TSAT ≥ 20%) yet still have anaemia associated with CKD will not achieve target haemoglobin levels without administration of ESAs. Should all patients regardless of the clinical situation and their functional status receive ESAs? Estimates of the number of people in England and Wales with significant CKD (eGFR <60 ml/min) and a haemoglobin level below 11 g/dl not currently receiving ESAs suggest that the potential number requiring anaemia management is 108,000. However, this estimate was made from an unselected population that will have included those with causes of anaemia other than CKD. A significant number may not have been iron replete, and the mean age of the cohort was 75.1 ± 11.63 years. The National Service Framework for Older People states that ‘NHS services will be provided, regardless of age, on the basis of clinical need alone’. For many older patients improvement in quality of life is their paramount need, and older people should not necessarily be excluded from these treatments. Becoming able to move around your house independently and therefore not needing admission to a care home would clearly be a successful outcome in treating anaemia.

The key goals in the management of anaemia are increased exercise capacity, improved quality of life, improved cognitive function, improved sexual function, reduced transfusion requirements, regression/prevention of left ventricular hypertrophy, improved morbidity, prevention of progression of renal disease, reduced risk of hospitalisation, and reduced mortality. We do not yet have the evidence that all of these goals are achievable and there may be certain patients whose physical and mental status renders these goals unachievable from the outset. Clearly these patients will not therefore benefit from administration of ESAs.

5.3.2. Methodological introduction

A comprehensive literature search did not identify any studies that were suitable to address the clinical or economic aspects of this section, therefore no evidence statements are given.

5.3.3. From evidence to recommendations

The GDG expected there to be a paucity of literature in this area. The reason for investigating the evidence base in this section was to determine whether there were any subgroups of patients in whom the administration of ESAs may be of little clinical benefit.

The GDG discussed whether they considered there were any patient subgroups with a Hb level below 11 g/dl and with stage 3–5CKD who should not be considered for treatment with ESAs. The GDG felt that it was a matter of clinical judgement, based on a patient’s individual circumstances (eg presence of comorbidities), as to whether a patient would benefit from the administration of ESAs.

The GDG considered it important to note that antibody mediated pure red cell aplasia (PRCA) does occur sporadically and this was one group of patients where epoetin administration should be very carefully considered.

The GDG felt the most relevant issue was how to best focus resources in the wider CKD population to provide the most benefit. The lack of evidence would suggest this is an area where research is required. The GDG discussed that where there is uncertainty over the benefits a patient may gain from ESA therapy, a trial of ESA therapy and assessment of response may be indicated prior to continuing long-term treatment. The GDG felt that the patient was a good judge of whether the treatment had any noticeable improvement on their quality of life and did not feel there was any need to recommend any formal tests. The GDG felt strongly that the decision to actively manage an individual patient’s anaemia should be made by an experienced clinician, but that this did not necessarily have to be a renal physician.

5.3.4. Recommendations

10.

The pros and cons of a trial of anaemia management should be discussed between the clinician, the person with anaemia of CKD and their families and carers if applicable. [D (GPP)]

11.

ESAs need not be administered where the presence of comorbidities, or the prognosis, is likely to negate the benefits of correcting the anaemia. [D (GPP)]

12.

A trial of anaemia correction should be initiated when there is uncertainty over whether the presence of comorbidities, or the prognosis, would negate benefit from correcting the anaemia with ESAs. [D (GPP)]

13.

Where a trial of ESA therapy has been performed, the effectiveness of the trial should be assessed after an agreed interval. Where appropriate, a mutual decision should be agreed between the clinician, the person with anaemia ofCKD and their families and carers on whether or not to continue ESA therapy. [D (GPP)]

14.

All people started on ESA therapy should be reviewed after an agreed interval in order to decide whether or not to continue using ESAs. [D(GPP)]

5.4. Nutritional supplements

5.4.1. Clinical introduction

Vitamins are essential cofactors that regulate the metabolic pathways from which lipids, proteins and carbohydrates are generated and processed. The uraemic environment is responsible for the development of significant alterations in serum levels, body stores and functions of many vitamins.

In patients with more advanced CKD (stages 4 and 5) the dietary restrictions imposed for potassium and phosphate inevitably limit the intake of some vitamins from natural sources. More recently dietary counselling has focused more on nutritional support than dietary restrictions, with people eating more liberal diets to try and optimise nutritional status. Currently there are no recommendations or guidance as to which population would benefit from vitamin supplementation and in what quantity. Much of our information about supplementation of vitamins comes from studies with small subject numbers, over short periods of time. Many of the studies only address vitamin requirements in the dialysis-dependent population, excluding predialysis patients.

Reasons to support vitamin supplementation include dietary restrictions, uraemic toxins, drug–nutrient interactions and the dialysis process itself. Water soluble vitamins are lost during both haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). However, this may be offset by the altered kinetics caused by renal failure which may result in reduced urinary losses or renal catabolism. The fact that CKD affects the normal absorption, retention and activity of the necessary micronutrients which support all aspects of carbohydrate, protein and lipid metabolism, further strengthens the evidence in favour of supplementation.

Less is known about the nutritional requirements of fat soluble vitamins in patients with CKD. Studies report anything from subnormal through normal to enhanced levels. In practice supplementation with fat soluble vitamins is not recommended.

Data remain incomplete on individual requirements of vitamins, the handling of vitamins in uraemia, the vitamin status of uraemic patients and the effect of vitamin administration.

Carnitine is synthesised in the body from two essential amino acids, lysine and methionine, whereas glutathione is a peptide containing the amino acids glutamic acid, cysteine and glycine. Carnitine and glutathione have both been implicated in enhancing responsiveness to EPO in CKD patients but there are few studies to date. In practice, this is not done routinely.

Although much is known about the prevalence of macronutrient deficiency in renal patients, nutritional status in CKD is beyond the scope of this guideline. This section focuses on micronutrient supplementation and its effect on the treatment of anaemia due to CKD.

5.4.2. Methodological introduction

A comprehensive literature search identified eight studies. Of these, two studies addressed vitamin C: a cross-over RCT119 and a non-randomised controlled trial307. One RCT addressed folic acid236. Five studies addressed carnitine supplementation, which consisted of three RCTs,47,159,164 a cross-over RCT280 and a before and after study179.

Eleven studies had methodological limitations and were thus excluded from the evidence statements. These include four which addressed vitamin C,156,284,308,310 one which addressed vitamin E227, one which addressed folate158, and five which addressed carnitine supplementation131,195,274,295,324.

Notable aspects of the evidence base were:

  • No studies addressing vitamin E or glutathione were found.
  • The meta-analysis investigating carnitine supplementation131 did not meet quality criteria, hence the studies within it47,159,164 were individually appraised.
  • One study was conducted in children179.
  • One study119 was conducted in a pre-selected patient population.

A comprehensive literature search did not identify any studies that were suitable to address the economic aspects of this section.

5.4.3. Evidence statements

Vitamin C

Haemodialysis patients

A non-randomised trial (n=52)307 where 100 mg ascorbic acid was administered i.v. three times weekly in one group (n=23) and as an adjunct to ESA and i.v. iron in another, found no significant change in Hb levels from baseline in either group after 6 months. In addition, no changes were identified in either group in any of the eight domains of quality of life assessed using the Short-Form 36 (SF 36) scale. (Level 2+)

In a randomised controlled trial (RCT) of cross-over design (n=27)119, where ascorbic acid 1,500 mg/week was administered i.v. for 3 months, Hb increased (p<0.01 in group I and p<0.005 in group II) and TSAT increased (both group I and group II p<0.001), whereas ferritin decreased (p<0.004 in group I and p<0.001 in group II) when compared with baseline levels. Epoetin doses, however, remained unchanged in both groups. (Level 1+)

Folic acid

Haemodialysis patients

Reticulocyte counts (both p<0.05) and Hct levels (both p<0.01) increased from baseline levels in both sets of patients receiving folic acid 5 mg three times a week over 12 months (n=10) and patients whose folic acid supplementation had been stopped over this time period (n=10). Hct levels increased further (both p<0.01) in the 6-month follow-up period after folic acid supplementation had been stopped in both groups of patients. There were no differences, however, in response to epoetin between the two groups236. (Level 1+)

Carnitine

Haemodialysis patients

No differences were observed in any of the five domains of quality of life as assessed by the Kidney Disease Questionnaire or in overall quality of life, in a RCT of cross-over design (n=16) in which placebo or 20 mg/kg L-carnitine were administered i.v. over a 12-week period. Similarly, no differences were observed in epoetin dose or Hb levels280. (Level 1+)

No differences were observed in epoetin dose requirement or Hct and reticulocyte counts in a 6-month study investigating the effects of supplementation with 1 g L-carnitine three times a week in elderly patients (n=28), after which patients were followed up for 3 months47. (Level 1+)

No differences were found when patients treated with epoetin were supplemented with 1 g carnitine three times a week or placebo(n=24) for 6 months and compared in terms of epoetin dose, endogenous epoetin levels or Hct and iron levels164. (Level 1+)

No significant changes in epoetin dose requirement were observed between patients supplemented with either 5 mg/kg (n=15) or 25 mg/kg (n=5) L-carnitine vs placebo (n=20) over 8 months. However, a greater reduction in change in epoetin dose was observed in the carnitine treated group (p<0.05) and a higher epoetin resistance index (epoetin dose:Hb ratio) (p<0.02). Additionally, after 4 months, there were significant negative correlations between plasma free carnitine, plasma total carnitine and plasma free carnitine:plasma total carnitine to EPO dose and ERI in both treatment groups159. (Level 1+)

Paediatric haemodialysis and peritoneal dialysis patients

Total carnitine and free carnitine increased significantly from baseline (both p <0.05) after 26 weeks treatment with orally administered L-carnitine 20 mg/kg daily in both haemodialysis (n=8) and peritoneal dialysis patients (n=4), with a mean age of 10.2 years. Acylcarnitine increased only in haemodialysis patients (n=8) after 26 weeks. Despite this, no changes were observed in Hblevels or epoetin dose from baseline in both sets of patients. In addition, no correlation was found between epoetin dose or Hb levels with total carnitine, free carnitine and acylcarnitine levels179. (Level 3)

5.4.4. From evidence to recommendations

It was concluded that there was no evidence to support the adjunctive use of vitamin C, folic acid or carnitine supplements in the treatment of anaemia of CKD. There was very little evidence available for the CKD population and no evidence in the predialysis population. It was considered acceptable to extrapolate the conclusions to the predialysis population.

With regard to vitamin C, the appraised studies administered very high doses (1,500 mg/wk, 1,000 mg/wk and 100 mg/wk). A dose of 50 mg/week was considered to be a more appropriate supplement given in clinical practice to renal patients. The biological basis for the administration of vitamin C was related to aiding the mobilisation of iron and promoting effective erythropoiesis. The evidence base was small.

In clinical practice, when patients are given folate supplements this is generally for other reasons than the correction of anaemia. The studies appraised on carnitine supplementation gave negative results.

5.4.5. Recommendation

15.

Supplements of vitamin C, folic acid or carnitine should not be prescribed as adjuvants specifically for the treatment of anaemia of CKD. [A]

5.5. Androgens

5.5.1. Clinical introduction

Interest in the use of androgens as adjunctive treatment in the management of anaemia associated with CKD stems from their use prior to the availability of ESAs. A number of early studies49,77,110,128,337 suggested a beneficial effect on renal anaemia by treatment with androgens, although notably one double blind cross-over trial of nandrolone decanoate failed to show a sustained significant effect on haemoglobin level or red cell mass213. However, their regular use was abandoned because of the requirement for parenteral administration and a number of adverse effects such as acne, flushing of skin, hirsutism, changes in voice, masculinisation, amenorrhoea and increasing libido, together with adverse effects related to liver function such as peliosis as well as hepatocellular adenoma and carcinoma.

The mechanism of action of androgens on erythropoiesis is still not completely understood and mechanisms proposed include increased production of endogenous erythropoietin, synergism with ESAs, enhanced sensitivity of erythroid precursors to erythropoietin, increased red cell survival, and a direct effect on erythroid precursors. There is thus a potential role for androgens in enhancing the effectiveness and reducing the dose requirements of available ESAs.

5.5.2. Methodological introduction

A literature search identified eight studies, including two RCTs118,224, three cohort studies26,312,313 and one before and after study169.

Two studies33,117 had methodological limitations and were therefore excluded from the evidence statements.

The GDG agreed that the following outcomes were priorities:

Notable aspects of the evidence base were:

  • The studies were investigating:
    • epoetin vs nandrolone224,313
    • epoetin vs epoetin and nandrolone26,118
    • epoetin and nandrolone (no control group)169
    • Nandrolone alone (no control group)312.
  • Although side effects were noted in some studies118,169,312, the authors did not attempt to quantify all of these.
  • The studies were conducted in both male and female patients except for two studies26,224, which were conducted solely in male patients.

5.5.3. Evidence statements

Hb/Hct levels

Haemodialysis patients

In a before and after study conducted in male (n=9) and female (n=8) patients169, Hb (p=0.001) and Hct (p=0.003) levels increased following adjuvant therapy with epoetin (3,000 U/week s.c.) and nandrolone decanoate (100 mg i.m. weekly) for 6 months. When stratified into sex of patients, Hb and Hct levels (both p=0.01) were higher only in female patients. (Level 3)

In a cohort study conducted in male (n=67) and female (n=17) patients312, Hb and Hct levels rose (both p<0.01) following 6 months’ therapy with nandrolone decanoate 200 mg i.m. weekly. Although baseline Hb levels were higher in the male patients (p<0.05), the increase with respect to baseline levels was similar in both sexes throughout the study. In order to evaluate the influence of other factors, patients were divided into the following:

  • non-responders (Hb increase <1 g/dl with respect to baseline; n=28)
  • mild responders (Hb increase 1–1.9 g/dl with respect to baseline; n=18)
  • good responders (Hb increase 2–2.9 g/dl with respect to baseline; n=25)
  • excellent responders (Hb increase >2.9 g/dl with respect to baseline; n=13).

Only age was significantly associated with response to androgen therapy (p<0.01). When the cohort was stratified into ages less than 46 years (n=29), 46–55 years (n=28) and more than 55 years (n=27), only the latter two groups showed improvement in Hblevels (both p<0.01) following androgen therapy. (Level 2+)

A 6-month cohort study conducted to compare the effect of 200 mg nandrolone decanoate i.m. once weekly in male patients aged over 50 years (n=18) vs epoetin 6,000 IU a week in male and female patients aged less than 50 years (n=22) found an increase inHb levels in both groups (both p<0.01), despite a drop in serum ferritin levels in the epoetin treatment group (p<0.01)313. (Level 2+)

In a cohort study26 conducted over 12 weeks in male patients treated with epoetin 6,000 U i.v. 3 times a week (n=7) vs epoetin 6,000 U i.v. 3 times a week and 100 mg nandrolone decanoate i.m. once a week (n=8), Hct values increased in the group receiving adjuvant therapy (p<0.001) after 12 weeks and no transfusions were required in either group. (Level 2+)

A RCT conducted in predominantly black male and female patients administered with epoetin 4,500 U per week vs epoetin 4,500 U per week (n=10; 4 men and 6 women) and nandrolone 100 mg i.m. once a week (n=9; 7 men and 2 women) over 26 weeks found a significant increase in Hct in both treatment groups when compared with baseline values (p=0.003 and p=0.001 respectively). However, the rise in Hct was greater in the epoetin plus androgen group (p=0.012) when compared with epoetin alone118. (Level 1+)

CAPD patients

Hb and Hct levels increased in both treatment groups in a RCT224 investigating influence of epoetin initiated at 50 U/kg/week and tailored to target Hb of 11–13 g/dl vs nandrolone 200 mg i.m. once weekly (both p<0.001) when compared with baseline values. However, these increases in Hb and Hct levels were not significantly different when the treatment groups were compared with each other. (Level 1+)

Epoetin dose

Haemodialysis patients

In a before and after study conducted in male (n=9) and female (n=8) patients169, weekly epoetin doses following adjuvant therapy with nandrolone decanoate (100 mg i.m. weekly for 6 months) did not change significantly, either in the overall cohort or when stratified into male and female patients. (Level 3)

In a cohort study conducted over 12 weeks in male patients treated with epoetin (6,000 U i.v. three times a week) (n=7) vs epoetin (6,000 U i.v. three times a week) and nandrolone decanoate 100 mg i.m. once a week (n=8), no difference was observed in epoetin dose between the two treatment groups26. (Level 2+)

Adverse events—serum triglycerides

Haemodialysis patients

In a cohort study conducted in male (n=67) and female (n=17) patients, serum triglycerides increased (p<0.01) after therapy with nandrolone decanoate 200 mg i.m. weekly for 6 months312. (Level 2+)

A 6-month cohort study conducted to compare the effect of nandrolone decanoate (200 mg i.m. once weekly) in male patients aged over 50 years (n=18) vs epoetin (6,000 IU a week) in male and female patients aged less than 50 years (n=22) found an increase in serum triglycerides in the androgen group (p<0.001)313. (Level 2+)

5.5.4. From evidence to recommendations

The rationale for the administration of androgens to patients with anaemia of CKD was historical in that androgens were administered in the pre-ESA era. The studies had administered nandrolone decanoate but this androgen is no longer used in clinical practice. The doses of nandrolone administered in the studies were considered to be supraphysiological. The group agreed that there was some evidence of efficacy in that the administration of androgens could reduce the dose of ESA required but were concerned about the potential side effects and considered this an outdated approach to anaemia management.

5.5.5. Recommendation

16.

In people with anaemia of CKD, androgens should not be used to treat the anaemia. [C]

5.6. Hyperparathyroidism

5.6.1. Clinical introduction

Elevations in serum parathyroid hormone (PTH) concentration (secondary hyperparathyroidism) are seen early in CKD and are common when the estimated GFR is <60 ml/min (stage 3 CKD onwards)263,296,325. Elevation of PTH in the stage 3 and 4 CKD populations predicts the development of more severe hyperparathyroidism, which in turn is clearly associated with increased skeletal and cardiovascular morbidity and mortality72. Whether hyperparathyroidism causes anaemia and resistance to treatment of anaemia, and if it does, what degree of hyperparathyroidism is clinically important, remain controversial. Potential mechanisms include a direct effect of PTH on endogenous erythropoietin synthesis, on bone marrow erythroid progenitors, and on red cell survival through accelerated haemolysis, and an indirect effect through induction of bone marrow fibrosis. This section looks at whether treatment of hyperparathyroidism in people with anaemia associated with CKD improves the management of anaemia in terms of haemoglobin level achieved and dose of ESA required, and also attempts to determine when treatment should be considered.

5.6.2. Methodological introduction

A literature search identified seven studies. These consisted of a cohort study72, a two-part study comprising a cohort study and prospective before and after study180, a two-part study comprising a prospective longitudinal study and cohort study121, a prospective before and after study and cohort study344, a prospective longitudinal study14, and two retrospective before and after studies58,262.

Six studies29,112,226,256,326,346 had methodological limitations and were therefore excluded from the evidence statements.

The GDG agreed that the following outcomes were priorities:

  • parathyroid hormone levels
  • mortality and morbidity
  • ESA dose
  • improved response to ESA
  • plasma erythropoietin levels
  • reduction in ESA resistance
  • Hb/Hct level.

Notable aspects of the evidence base were:

  • Treatment for parathyroidism was stratified into drug-based with calcitriol121,180, alfacalcidol14, or surgery58,72,168,262.

A comprehensive literature search did not identify any studies that were suitable to address the economic aspects of this section, therefore no health economic evidence statements are given.

5.6.3. Evidence statements

Table 5.1Summary of evidence for appraised studies

Reference Drug-based therapy Sample size Baseline iPTH levels (pg/ml) Treatment duration Outcome Effect Level of evidence
180 Calcitriol 2 μg n=16 778 ± 172.7 6 months n=7 responders Level 2+
iPTH
Hct
Epoetin dose
14 Alfacalcidol 6 mg n=12 ~475 18 months iPTH Level 3
Hb
121 Calcitriol i.v.2 μg n=28 811.6 ± 327 12 months Hb/Hct Level 3
IPTH
121 Calcitriol i.v.2 μg n=28 811.6 ± 327 12 months Epoetin use (n=21) vs No Epoetin (n=7) Epoetin dose No change Level 2+
121 Calcitriol i.v.2 μg n=28 811.6 ± 327 12 months Responders (n=19) vs non- responders (n=9) Level 2+
Hct
Epoetin dose No change
Author/Study ID Surgical procedure Sample size Basal iPTH levels (pg/ml) Length of follow- up after surgery Outcome Effect Level of evidence
262 Subtotal parathyroidectomy (n=9) and total parathyroidectomy with forearm autotransplantation (n=1) n=10 Not reported 6 months iPTH Level 3
Hct
Epoetin dose
180 Total parathyroidectomy with forearm autotransplantation n=3 976 ± 436.1 6 months iPTH Level 3+
Hct
Epoetin dose
58 Subtotal parathyroidectomy n=19 1,726 ± 1,347 1–2 years (n=44) Hb No change Level 3
Total parathyroidectomy and autotransplantation n=10 913 ± 380 3–5 years (n=24) Hb
Total parathyroidectomy n=10 1,006 ± 668
Partial parathyroidectomy (removal of 2–3 parathyroid glands) n=6 1,176 ± 3346
344 Total parathyroidectomy and forearm autotransplantation n=29 Note n=7 underwent reoperation for recurrences in neck and forearm 873 ± 710.8 12 months iPTH Level 3
Hb
Plasma erythropoietin
12 months Epoetin use (n=23) vs No Epoetin (n=6)
Epoetin dose
No change Level 2+
168 Total parathyroidectomy and forearm autotransplantation n=32
1,338 ± 350.6
Responders
Non-responders 1,228 ± 290.8
3 months n=17 responders (≥10% Hbincrease post-PTX) vs n=15 non-responder No change
No change
No difference
Level 2+
Hb Serum erythropoietin but no difference between the 2 groups
iPTH

↑ = significant increase;

↓ = significant decrease;

PTX = parathyroidectomy.

5.6.4. From evidence to recommendations

Treatment of hyperparathyroidism secondary to CKD is part of good clinical practice as is routine monitoring of PTH levels in patients with CKD. Early control of hyperparathyroidism is crucial for preventing metabolic bone disease and treating hyperparathyroidism is beneficial to anaemia management. The strategies used do not differ in patients with CKD whether they are anaemic or not. On the evidence available, it was not felt to be appropriate to recommend specific interventions and the British266, American194 and European4 treatment guidelines in the management of renal osteodystrophy which are aimed at attainment of target PTH, calcium and phosphate concentrations should be followed.

5.6.5. Recommendation

17.

In people with anaemia of CKD, clinically relevant hyperparathyroidism should be treated to improve the management of the anaemia. [C]

5.7. Patient-centred care: ESAs

5.7.1. Clinical introduction

The ESAs currently available in clinical practice differ in terms of frequency of administration and route of administration. The ESAs currently available in clinical practice may be administered either subcutaneously or intravenously. Darbepoetin is likely to require less frequent administration than the erythropoietins, while the erythropoietins are likely to require less frequent administration and a lower dose when administered subcutaneously vs intravenously. Logistically it is easier for patients not on haemodialysis to receive ESAs subcutaneously by self-administration or administration by their carer/practice nurse at home; patients on haemodialysis may also elect to receive their ESA either through self-administration or from dialysis staff at the end of haemodialysis.

Key considerations for patients with anaemia associated with kidney disease are that:

  • ESAs are prescribed when clinically indicated.
  • The ESA supply, route of supply and storage arrangements are clearly defined, secure and convenient.
  • The administration and monitoring of anaemia treatment is as efficient, comfortable and least disruptive as possible.

5.7.2. Methodological introduction

Seven studies were identified, including two RCTs123,211, one of which was of cross-over design123, one retrospective longitudinal study334, one retrospective case series230, and three cross-sectional studies19,191,223.

One study25 had methodological limitations and was thus excluded from the evidence statements. The buffer used in the preparation in the cross-over study123 is no longer used, and the paper was therefore not considered further.

Notable aspects of the evidence base were:

  • The studies conducted using questionnaires were limited by the use of closed questions in their design191,223,334, with the exception of one study19, which reported the use of both closed and open questions.
  • All the studies using questionnaires were cross-sectional, with the exception of one study334, which was of longitudinal design.

A comprehensive literature search did not identify any studies that were suitable to address the economic aspects of this section, therefore no evidence statements are given.

5.7.3. Evidence statements

Route of administration – effect on quality of life

Haemodialysis patients

In a 24-week cross-over study211 where s.c. was compared with i.v. administration, quality of life assessed by means of the Kidney Disease Questionnaire (KDQ), which consists of five domains, found improvements from epoetin administration (both intravenous and subcutaneous) in the physical (p<0.05) and fatigue (p<0.05) domains, but no significant differences between the two modes of administration in any other domains123. (Level 1+)

Adherence and ESA administration

Peritoneal dialysis patients

In a retrospective longitudinal study334, 19 of 54 (35%) patients administering s.c. epoetin in the home setting were non-concordant (defined as less than 90% of the prescribed dose used), with the most commonly reported reason being forgetfulness. Missing dialysis exchanges, completion of secondary education and younger age were found to be independent predictors of non-adherence (r2=0.36). (Level 3)

In a retrospective study230, 30 of 55 (55%) patients administering epoetin s.c. in the home setting were non-concordant (defined as less than 90% of the prescribed dose used). Whether another person administered the ESA on behalf of the patient was the only significant correlation with concordance (r=0.46, p=0.005). (Level 3)

Haemodialysis and continuous ambulatory and automated peritoneal dialysis patients

In a cross-sectional study191, concordance ranged from 24–33%, with the over-60 age group least likely to miss an epoetin dose and reduced frequency of administration associated with less missed doses. The majority of patients were likely to self-administer. Fewer injections were preferred by 72.5%, with the under-60 age group preferring once-weekly because of convenience, pain on injection and epoetin storage. (Level 3)

Predialysis, hospital and home haemodialysis and continuous ambulatory peritoneal dialysis patients

In a cross-sectional study19, 57 of 86 (66%) patients reported they never missed doses, while 31% admitted to occasionally missing doses and 3% admitted to frequently missing doses. Following a missed dose, the majority (39%) informed the renal unit, 27% carried on as usual after the missed dose, 19% administered the missed dose as soon as they remembered. The majority (55%) of patients preferred self-administration of epoetin, with 17% reporting difficulties with injection preparation and 17% reporting pain at the injection site. (Level 3)

Communication and obtaining of ESA

Predialysis, hospital and home haemodialysis and continuous ambulatory peritoneal dialysis patients

In a cross-sectional study19, the majority of patients (89%) reported the renal unit anaemia nurse to be the preferred source of information. However, most patients (59%) reported they did not need more information. Most requests for information were found to be about how epoetin works (31%), possible side effects (29%) and what epoetin is for (26%). Epoetin supply was found to be mostly by GPs (71%), although 20 patients (23%) reported that their GPs had refused to supply epoetin. Most patients preferred obtaining epoetin supplies from a community pharmacy (n=63). (Level 3)

Predialysis, dialysis and transplant patients

In a cross-sectional study223, most (91%) anaemic patients received epoetin therapy. Of the 4% that were refused epoetin, the reasons given were that the GP could not pay for it (50%) and that the hospital could not pay for it (20%). (Level 3)

EPO administration – effect on quality of life

Predialysis, dialysis and transplant patients

In a cross-sectional study223, sleep disturbance, tiredness and ability to attend a 9am to 5pm job were found to be associated with baseline Hb and post-treatment levels. Patients whose post-treatment Hb levels had increased from below 11 g/dl to above 11 g/dl were 1.8 times more likely to report an improvement in QoL. Patients with post-treatment Hb levels >11 g/dl were 1.9 times more likely to agree with the statement ‘I can attend a 9am 5pm job’. (Level 3)

5.7.4. From evidence to recommendations

The evidence from seven studies contained outcome data on quality of life, pain, concordance, obtaining ESAs and communication with patients.

The data supported the view that patient preferences and experiences should be taken into account, where possible, when decisions are reached about treatment with ESAs. The patient should be given access to sufficient information about their condition and its treatment to allow them to make informed choices about the management of their condition (for example, whether to have supervised- or self-administration of ESAs). It was noted that some studies had shown an increased lack of concordancein some groups who had chosen self-administration230,334. Patients need to be aware of the consequences of poor concordance and one study highlighted that a reduced frequency of administration of ESAs resulted in increased concordance191. Currently many patients have difficulties securing a supply of ESAs. Many patients are unable to obtain ESAs from their local hospital or GP practice and have the ESAs delivered to them at home. This can cause problems in finding the capacity to refrigerate large quantities of drugs. This area needs to be addressed by healthcare providers to ensure adequate drug supply and storage facilities for patients.

5.7.5. Recommendations

18.

People offered ESA therapy, and their GPs, should be given information about why ESA therapy is required, how it works, and what benefits and side effects may be experienced. [D]

19.

When managing the treatment of people with anaemia of CKD, there should be agreed protocols defining roles and responsibilities of healthcare professionals in primary and secondary care. [D(GPP)]

20.

People receiving ESA therapy should be informed about the importance of concordance with therapy and the consequences of poor concordance. [D]

21.

When prescribing ESA therapy, healthcare professionals should take into account patient preferences about supervised- or self-administration, dose frequency, pain on injection, method of supplying ESA and storage.[D(GPP)]

22.

In order for people to self-administer their ESA in a way that is clinically effective and safe, arrangements should be made to provide ready, reasonable and uninterrupted access to supplies. [D]

5.8. Patient education programmes

5.8.1. Clinical introduction

Patient self-management is one of the cornerstones of chronic disease management, enabling patients some degree of control of their own disease process. The level of independence each individual achieves depends as much on the quality of the information and self-management tools provided as it does on the ability of the individual patient. Patient education programmes are therefore of paramount importance in achieving effective patient self-management.

Structured patient education involves planned education that covers all aspects of anaemia management and is flexible in content, is relevant to a person’s clinical and psychological needs, and is adaptable to their educational and cultural background. A well-planned education course will provide a written outline, be delivered by trained educators (preferably someone who is both well versed in the principles of patient education and is competent to teach the programme), be quality assured, and provide the opportunity for feedback.

5.8.2. Methodological introduction

A comprehensive literature search did not identify any clinical or health economic studies that were suitable to address this section.

5.8.3. From evidence to recommendations

Patient education was considered to be hugely important and information should be available at different levels. Adequate information helps patients to make decisions about their treatment and illness, although it was noted that there might be some patients who will wish to remain passive about their condition.

Patient education should meet the individual needs of each patient and five themes drawn from recent work in the area272 were considered to be important:

  • practical management of anaemia
  • knowledge (about symptoms, iron and ESA management and product delivery and storage)
  • professional support (contact information, community services, continuity of care, monitoring, feedback on progress of results)
  • lifestyle (diet, physical exercise, maintaining normality, meeting other patients)
  • adaptation (causes of anaemia, associated medications, phases of treatment, previous information and expectations, resolution of symptoms).

5.8.4. Recommendation

23.

Culturally and age-appropriate patient education programmes should be offered to all people diagnosed with anaemia of CKD and their families and carers. These should be repeated as requested, and according to the changing circumstances of the patient. They should include the following key areas:

  • practical information about how anaemia of CKD is managed
  • knowledge (eg about symptoms, iron management, causes of anaemia, associated medications, phases of treatment)
  • professional support (eg contact information, community services, continuity of care, monitoring, feedback on progress of results)
  • lifestyle (eg diet, physical exercise, maintaining normality, meeting other patients)
  • adaptation to chronic disease (eg previous information and expectations, resolution of symptoms).

Remains of an ancient universe


WMAP map of a region of space that is cooler than its surroundings.

Wikimedia CommonsWMAP map of a region of space that is cooler than its surroundings.

Two precision studies of the remnants of the Big Bang are almost in agreement about what they have found… almost.

In the 2000s, two space probes set out to study the relics of an ancient chaos in exacting detail. Their subject was a tremendous smattering of matter and radiation across trillions of light-years, possibly all the way across the universe. Scientists believe these relics hold the complicated clues to our universe’s origins, why the laws of nature are what they are, even why the hundreds of billions of galaxies are where they are now.

The chaos itself, whose residue interests us, was caused by an event popularly called the Big Bang, and its immediate aftermath. In 2001, the Wilkinson Microwave Anisotropy Probe(WMAP) was launched by NASA; in 2009, the European Space Agency launched thePlanck space-probe. While both probes studied the relic entity and produced agreeing results of the bigger picture, they do have smaller inconsistencies between them – inconsistencies physicists think need resolving because of the very-high sensitivities the instruments boast of.

Even if one of them is proved right and other wrong, our knowledge of the universe’s origins, pieced together since a monumental discovery in the 1960s, would change.

The story began in 1964 at the Bell Telephone Laboratory in New Jersey, where a radio antenna was being readied for a specific task: to listen to radio-waves being emanated by the Milky Way galaxy. The two astronomers who were going to make the observations, Arno Penzias and Robert Wilson, decided to start with a short wavelength of 7.35 cm. This was being done so they could check for static noise being generated by the antenna itself, before moving on to more precise readings. However, they were in for a pleasant surprise.

Cooking up heavier elements

They were able to discern a faint excessive signal of microwave radiation at 7.35 cm. No matter which way they turned the antenna, the signal persisted, meaning that it was coming in from all parts of the sky, not just specific areas. Because they’d known that pigeons had roosted in the past around the antenna’s receivers, they cleaned out those areas… but the eerie signal kept on. Penzias and Wilson used the signals strength to calculate the temperature of the objects that could be producing it – it was found to be about 3.5 K (–269.65 degrees Celsius).

They didn’t know what to make of it.

Around the same time, in March 1965, an astrophysicist named P.J.E. Peebles from Princeton University was trying to understand a strange anomaly. In the few minutes succeeding the Big Bang, the universe should have resembled a massive cauldron, with its ingredients being quickly cooked into bigger and bigger lumps of heavier elements. Today, however, fully three-quarters of matter in the universe is hydrogen. Where are the heavier elements?

Peebles surmised that there also must have been a lot of short-wavelength radiation that blasted heavier atoms apart as soon as they formed, preventing the mass-cooking of hydrogen into heavier nuclei of the metals. Further, his calculations showed that the radiation should have survived to this day, leaving the universe with a low but prevailing temperature of around 10 K. To see if he was right, Peebles and his colleagues, Robert Dicke, P.G. Roll and D.T. Wilkinson, started to set up an antenna to look for the signal from this radiation…

… when Dicke received a called from Penzias. Together, the five of them published a pair of papers in the Astrophysical Journal speculating on the implications of their finding. It was July 1965, and the start of a fascinating quest.

Relic radiation

In the decades since, physicists have been able to piece together the story of how this radiation could have originated, what it has to do with the Big Bang, and how a rapidly expanding universe’s signatures could have impinged on it. One of the first probes launched to study this relic radiation – called thecosmic microwave background (CMB) radiation – was the Cosmic Background Explorer, in 1989. This also marked the rise of cosmology, the study of the universe’s life.

In the moments immediately succeeding the Big Bang, the universe was seething hot and dense – protons, neutrons, electrons and photons were scattered about, their energy making them restless enough to resist entrapment into atoms. After 10-32 seconds, the volume of space started to expand rapidly – a period called the inflationary epoch which lasted for one microsecond but left the universe at least (hold your breath) 1 million trillion trillion trillion trillion trillion trillion times more voluminous.

After around 380,000 years, the temperature had dropped to about 3,000 K, and the first atoms formed. Because the electrons and radiation had existed in an equilibrium until then, the formation of atoms meant electrons were being used up, leaving the radiation to ‘move around’ and expand freely.

Thus formed the CMB radiation.

Because any change in the way it formed, howsoever small, would have altered it in significant proportions as it expanded, it was essential to know how precisely the CMB was distributed throughout the universe. Between 1990 and 1993, the Cosmic Background Explorer’s results presented the first view of the CMB on a vast scale.

Map of the universe

The Explorer’s successor was the Wilkinson Microwave Anistropy Probe (WMAP), launched in 2001. It is named for D.T. Wilkinson. In 2003, the WMAP presented its first results, considered to be groundbreaking for their immense detail, laying the foundation for a model of the universe that cosmologists abide by: the Lambda-CDM model. CDM here stands for ‘cold dark matter’, which WMAP found made up about 24 per cent of the universe. Of the remaining, 71 per cent came from dark energy while the rest was ordinary matter. It also measured the Hubble constant – the rate of the universe’s expansion – to be about 67.8 km/s/Mpc (interpreted as an object 1 megaparsec away moving away from the observer at 67.8 km/s).

In 2009, another probe, called simply Planck, was launched to study the CMB, as well as to investigate other cosmological problems. Planck boasted of a resolution thrice as much as WMAP’s, and could make its observations in nine frequency bands – as opposed to the one band that Penzias and Wilson used or the five bands that WMAP used. In fact, in order to achieve the precision that it did, the entire spacecraft was maintained at a temperature of 0.1 K, making it the coldest object in space!

By July 2010, Planck had completed an all-sky survey. On March 21, 2013, the results of its CMB-study were published. They were found mostly to be in agreement with the Lambda-CDM model, and the WMAP results by extension: according to Planck, the universe was 26.8 per cent dark matter, 68.3 per cent dark energy, and 4.9 per cent ordinary matter. The Hubble constant was pegged at a little less than 67.8 km/s/Mpc.

One thing that the Explorer, WMAP and Planck had all found was this: the CMB radiation was not evenly spread throughout the universe, but consisted of fluctuating ripples spreading across vast distances. This observation, called anisotropy, was attributed to minor irregularities in the way the radiation must have been packed together, predating its expansion for almost 14 billion years – the age of the universe. The experimental observation of this anisotropy was hailed as a major breakthrough in 1992.

The ‘Almost’

On the other hand, the Planck results didn’t fall in line with the WMAP results on some counts. Among the nine frequency bands that Planck had made its measurements in, the sixth band (217 GHz) was the source of concern. The data analysis team behind WMAP argued that with the exception of this band, all other bands agreed with the WMAP results.

It was an important problem because even though the inconsistencies were minor, Planck’s high precision meant that they could lead to significant alterations of our knowledge of the universe if they were true. For instance, it could place more weight on why Planck data differs from WMAP’s on the universe’s composition, or why Planck has found the universe to be expanding at a slightly slower rate than the WMAP found it to be. Perhaps, between the sensitivity of the two instruments, there might be unknown physical processes at work.

At the time (2013), the Planck team responded saying they do stand by their observations, and that the inconsistencies could be due to “the improved performance of the Planck data”. However, they did also agree to revisit their observations. Its outcome was released last week in the February 6 issue of Natureas a correspondence.

Jan Tauber, who leads the Planck science team, has concluded that the difference in values between the Planck and WMAP results are within one standard-deviation of each other. More importantly, he wrote that they differed because of “methodological variations between the respective analyses rather than by systematic errors in the Planck data”. Tauber also stated that “the small, time-dependent systematic errors … have little impact on the Planck Collaboration’s cosmological results”.

That Tauber was able to say that the results’ deviation had little impact means the Lambda-CDM model can continue to be the ‘standard model’ of cosmology in its present form. Even though it might have been presumptuous to assume something paradigm-altering could have come out of this debate, cosmology is heavily reliant on precision-measurements of extremely small values. Even a seemingly trivial deviation would imply a relatively more consequential deviation of the value before the inflationary epoch.

For example, going by the Planck and WMAP maps, a tiny unevenness of energy in the pre-inflationary CMB could have snowballed into the gargantuan galactic clusters we see today. Calculating the other way, we could ask: is some region of space colder than the CMB because of an accumulation of dark energy?

Europe’s gravity-surveying ‘Ferrari’ satellite plummeting to Earth.


A satellite that mapped the Earth’s gravity for four years has been caught by its pull and, with the mission over, started its uncontrollable descent, the ESA’s first re-entry of this kind since 1987.

Image from earth.esa.int

Now, with the xenon gas expired, scientists at the European Space Agency have literally no way of steering the vessel, so hopes are high everything will go smoothly and no damage will be caused down on Earth.. 

It was 25 years ago that the ESA last attempted such a free-fall, during the Isee-2 magnetosphere mission.

“Reentry into the atmosphere [is] probably less than two days away,” Christoph Stieger, the European Space Agency’s operations manager for the satellite, said in a status report on the ESA’s website. 

The space agency’s one-ton Gravity field and steady-state Ocean Circulation Explorer, or GOCE, was launched from Plesetsk, in northern Russia, in 2009. 

Reuters

Having spent 2 1/2 more years on its mission than originally planned, it was taken to extremely low orbits with the aim of providing gravity data of unparalleled accuracy. 

“This innovative mission has been a challenge for the entire team involved: from building the first gradiometer for space to maintaining such a low orbit in constant free-fall, to lowering the orbit even further,” said Volker Liebig, ESA’s director of Earth observation programs. “The outcome is fantastic. We have obtained the most accurate gravity data ever available to scientists. This alone proves that GOCE was worth the effort – and new scientific results are emerging constantly.” 

The $466 million satellite’s sleek aerodynamic design led to it being nicknamed the Ferrari of space.”

In late October, the satellite’s supply of xenon gas ran out; however, for two more weeks the satellite continued its orbit until its engines died and it started the inevitable fall to Earth. 

The problem scientists are faced with now is, despite knowing that most of GOCE will burn up in Earth’s atmosphere, around 50 fragments of debris weighing in at about 275 kilograms will slip past it. This means they could end up falling literally anywhere. 

The lack of knowledge is caused by constant changes in the Earth’s upper atmosphere, which are influenced by solar activity. 

An international campaign involving the Inter-Agency Space Debris Coordination Committee is monitoring the situation continuously, the ESA said, promising to “keep the relevant authorities permanently updated.” 

Scientists at NASA estimate that an average of one piece of falling space debris daily survives the Earth’s atmosphere. They are confident that the chances of debris causing serious damage are small, as the record of even property damage has been almost negligible in the last half-century. 

That assumption is based on the simple fact that two-thirds of the planet is covered in water, and that most of the Earth’s land masses are quite sparsely populated.

Russian, American and German satellites have fallen in the past, often in circumstances involving the failure of an engine at very low orbits. Though no substantial damage was ever reported, debris as heavy as 160-400 kilograms had previously fallen within hundreds of kilometers of populated areas in the Pacific.

Europe Launches Space Metal 3D Printing Project.


The European Space Agency has rolled out a new initiative to refine 3D printing techniques to make space-grade metal parts.

The project, called AMAZE, aims to spur innovations that could one day allow astronauts to print their own metal tools aboard the International Space Station or let engineers on the ground to print entire satellites.

3D printing, or additive manufacturing, builds solid objects from a series of layers, typically by melting powder or wire materials. This technique can produce complex structures with more flexibility and less waste than traditional manufacturing, which could translate into big cost and time savings. . [Photos: ESA’s AMAZE Space Metal 3D Printing Project.

Billed as the world’s largest metal 3D-printing project, ESA’s initiative brings together 28 industrial partners across the continent. AMAZE is short for Additive Manufacturing Aiming Towards Zero Waste and Efficient Production of High-Tech Metal Products.

“We want to build the best quality metal products ever made,” David Jarvis, ESA’s Head of New Materials and Energy Research, said in a statement when the project was unveiled last week at the London Science Museum.

The group is focusing on making space-quality components by using lasers, electron beams and even plasma to melt metal alloys, Jarvis explained. The project also aims to explore the possibility of combining strong and lightweight, but more exotic metals, such as tungsten, niobium and platinum, though these materials are expensive.

As part of the initiative, four pilot 3D printing-factories are being established in Germany, Italy, Norway and the United Kingdom. David wants to help standardize the technique and bring it to the mainstream, connecting key players in the metallic 3D printing business to develop a supply chain.

Titanium Printed Structure

ESA officials say innovations along the way to make 3D printers more viable for spacecraft could have benefits on Earth, leading to improvements in aircraft wings, jet engines and automotive systems.

ESA is hardly alone in its ambition to perfect metal 3D printing for the final frontier. Among several other NASA endeavors in additive manufacturing, the U.S. space agency recently completed a successful hot-fire test of the biggest 3D-printed rocket part built to date: an engine injector printed with nickel-chromium alloy powder.

There are several private and university-led efforts, too. Earlier this month, a group of students at the University of California, San Diego performed their first test of a 3D-printed engine made from cobalt chromium.

Pillownauts Rest For Science.


Ah, the things we do for the sake of scientific inquiry. These volunteers for the European Space Agency just got out of bed for the first time in 21 days. To examine the effects of spaceflight on astronauts’ bodies, the “pillownauts” laid at a 6 degree angle with their feet up in a medical facility in Toulouse, France while scientists poked and prodded them for three weeks.

No bathrooms, no showers, no getting up for a quick stretch. The paid volunteers were subjected to a strict high-protein, high-salt diet and an exercise routine “that involves pushing the volunteers down onto vibrating plates while doing upside-down squats,” according to ESA. Researchers from the University of Bonne hypothesized that this diet and exercise routine might lessen the bone and muscle loss associated with long-term missions in microgravity. The crazy sci-fi headgear they’re wearing is designed to measure how much oxygen each person breathes in and how much carbon dioxide comes out, as a way to study the links between diet, breathing and energy consumption.

Lasers Boost Space Communications.


Before NASA even existed, science-fiction writer Arthur C. Clarke in 1945 imaginedspacecraft that could send messages back to Earth using beams of light. After decades of setbacks and dead ends, the technology to do this is finally coming of age.

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Two spacecraft set for launch in the coming weeks will carry lasers that allow data to be transferred faster than ever before. One, scheduled for take-off on 5 September, is NASA’s Lunar Atmosphere and Dust Environment Explorer (LADEE), a mission that will beam video and scientific data from the Moon. The other, a European Space Agency (ESA) project called Alphasat, is due to launch on 25 July, and will be the first optical satellite to collect large amounts of scientific data from other satellites.

“This is a big step forward,” says Hamid Hemmati, a specialist in optical communications at NASA’s Jet Propulsion Laboratory in Pasadena, California. “Europe is going beyond demonstrations for the first time and making operational use of the technology.”

These lasers could provide bigger pipes for a coming flood of space information. New Earth-observation satellites promise to deliver petabytes of data every year. Missions such as the Mars Reconnaissance Orbiter (MRO) already have constraints on the volume of data they can send back because of fluctuations in download rates tied to a spacecraft’s varying distance from Earth. “Right now, we’re really far from Earth, so we can’t fit as many images in our downlink,” says Ingrid Daubar, who works on the MRO’s HiRISE camera at the University of Arizona in Tucson. Laser data highways could ultimately allow space agencies to kit their spacecraft with more sophisticated equipment, says John Keller, deputy project scientist for NASA’s Lunar Reconnaissance Orbiter (LRO). That is not yet possible, he says. “We’re limited by the rate at which we can download the data.”

Today’s spacecraft send and receive messages using radio waves. The frequencies used are hundreds of times higher than those put out by music stations on Earth and can cram in more information, allowing orbital broadcasts to transmit hundreds of megabits of information per second. Lasers, which operate at higher frequencies still, can reach gigabits per second (see ‘Tuned in’). And unlike the radio portion of the electromagnetic spectrum, which is crowded and carefully apportioned, optical wavelengths are underused and unregulated.

Efforts to develop laser communication systems struggled for much of the twentieth century: weak lasers and problematic detectors derailed project after project. But recent advances in optics have begun to change the situation. “The technology has matured,” says Frank Heine, chief scientist at Tesat-Spacecom, a company based in Backnang, Germany.

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In the 1980s, Europe took advantage of improved lasers and optical detectors to begin work on its first laser communication system, the Semiconductor Laser Intersatellite Link Experiment (SILEX). Equipped with the system, the ESA satellite Artemis received 50 megabits of information per second from a French satellite in 2001and then exchanged messages with a Japanese satellite in 2005. The project taught engineers how to stabilize and point a laser in space. But it was abandoned after its intended application — a constellation of satellites to provide Internet services — was dropped in favor of the network of fiber-optic cables now criss-crossing the globe.

Since then, Heine’s team at Tesat-Spacecom has created a laser terminal for satellite-to-satellite communication, at a cost to the German Aerospace Center of €95 million (US$124 million). The laser, amplified by modern fiber-optic technology, achieves a power of watts — compared with the tens of milliwatts reached by SILEX. In 2008, terminals mounted on two satellites transferred information at gigabits per second over a few thousand kilometers.

ESA’s Alphasat will extend the range of this laser terminal to tens of thousands of kilometers once it is positioned high in geostationary orbit. Future satellites that sport laser terminals in lower orbits will be able to beam as much as 1.8 gigabits per second of information up to Alphasat, which will then relay the data to the ground using radio waves. Alphasat’s geostationary orbit means that it can provide a constant flow of data to its ground station — unlike low-Earth-orbit satellites, which can communicate with the ground for only an hour or two each day as they race by overhead. “Other satellites will be able to buy time on our laser terminal,” says Philippe Sivac, Alphasat’s acting project manager.

One client will be another ESA mission due to launch this year: Sentinel-1, the first of several spacecraft to be sent up for Europe’s new global environmental-monitoring program Copernicus. It will beam weather data to Alphasat until the end of 2014. At that point, Europe plans to start deploying a network of dedicated laser-relay satellites that will ultimately handle 6 terabytes of images, surface-temperature measurements and other data collected every day by a fleet of Sentinel spacecraft.

But Europe’s space lasers have a significant drawback. Although they can shuttle information between spacecraft, they have trouble talking to the ground — a task that must still be performed by radio waves. This is because these lasers encode information by slightly varying the frequency of light in a way analogous to modulating an FM radio station. A beam modulated in this way is protected from solar interference but is vulnerable to atmospheric turbulence.

The laser on NASA’s upcoming LADEE mission will communicate directly with Earth using a different approach that is less susceptible to atmospheric interference. It encodes information AM-style by tweaking the amplitudes rather than the frequency of a light wave’s peaks.

NASA hopes that the LADEE demonstration will extend laser communications beyond Earth’s immediate vicinity, to the Moon and other planets. Deep-space missions currently rely on radio transmissions. But radio waves spread out when they travel long distances, weakening the signal and reducing the data-transfer rate.

Laser beams, by contrast, keep their focus, allowing them to shuttle the already greater quantities of information they encode over longer distances without using the extra power needed by radio transmitters. “Laser communication becomes more advantageous the farther out you go,” says Donald Cornwell, mission manager for the Lunar Laser Communication Demonstration project on LADEE at NASA’s Goddard Space Flight Center in Greenbelt, Maryland.

In 1992, the Galileo probe, on its way to Jupiter, spotted laser pulses sent more than 6 million kilometers from Earth. A laser on Earth pinged the Mars Global Surveyor in 2005. Another struck the MESSENGER mission en route to Mercury, which responded with its own laser pulses. In January this year, the Lunar Reconnaissance Orbiter received the first primitive message sent by laser to the Moon — an image of the Mona Lisa that travelled pixel by pixel in a sort of Morse code.

LADEE carries NASA’s first dedicated laser communications system. With a bandwidth of 622 megabits per second, more than six times what is possible with radio from the distance of the Moon, the system can broadcast high-definition television-quality video. But even though its AM optical system is good at penetrating Earth’s turbulent atmosphere, it will still need a backup radio link for cloudy days when the laser is blocked. To minimize this problem, LADEE’s primary ground station is in a largely cloudless desert in New Mexico, with alternative sites in two other sunny spots: California and the Canary Islands.

Source: http://www.scientificamerican.com

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