Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Involving disabled children and young people as partners in research: a systematic review.

Children and young people can be valuable partners in research, giving their unique perspectives on what and how research should be done. However, disabled children are less commonly involved in research than their non-disabled peers. This review investigated how disabled children have been involved as research partners; specifically how they have been recruited, the practicalities and challenges of involvement and how these have been overcome, and impacts of involvement for research, and disabled children and young people. The INVOLVE definition of involvement and the Equality and Human Rights Commission definition of disability were used. Relevant bibliographic databases were searched. Websites were searched for grey literature. Included studies had involved disabled children and young people aged 5-25 years in any study design. Reviews, guidelines, reports and other documents from the grey literature were eligible for inclusion. Twenty-two papers were included: seven reviews, eight original research papers, three reports, three guidelines and one webpage. Nine examples of involvement were identified. Recommendations included developing effective communication techniques, using flexible methods that can be adapted to needs and preferences, and ensuring that sufficient support and funding is available for researchers undertaking involvement. Positive impacts of involvement for disabled children included increased confidence, self-esteem and independence. Positive impacts for research were identified. Involving disabled children in research can present challenges; many of these can be overcome with sufficient time, planning and resources. More needs to be done to find ways to involve those with non-verbal communication. Generally, few details were reported about disabled children and young people's involvement in studies, and the quality of evidence was low. Although a range of positive impacts were identified, the majority of these were authors' opinions rather than data. There remains scope for methodological research to inform appropriate approaches to public and patient involvement in childhood disability research.

Observation of electron-antineutrino disappearance at Daya Bay.

The Daya Bay Reactor Neutrino Experiment has measured a nonzero value for the neutrino mixing angle θ(13) with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GWth reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43,000 ton-GWth-day live-time exposure in 55 days, 10,416 (80,376) electron-antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is R=0.940±0.011(stat.)±0.004(syst.). A rate-only analysis finds sin(2)2θ(13)=0.092±0.016(stat.)±0.005(syst.) in a three-neutrino framework.

Does participating in physical activity in outdoor natural environments have a greater effect on physical and mental wellbeing than physical activity indoors? A systematic review.

Our objective was to compare the effects on mental and physical wellbeing, health related quality of life and long-term adherence to physical activity, of participation in physical activity in natural environments compared with physical activity indoors. We conducted a systematic review using the following data sources: Medline, Embase, Psychinfo, GreenFILE, SportDISCUS, The Cochrane Library, Science Citation Index Expanded, Social Sciences Citation Index, Arts and Humanities Citation Index, Conference Proceedings Citation Index--Science and BIOSIS from inception to June 2010. Internet searches of relevant Web sites, hand searches of relevant journals, and the reference lists of included papers and other review papers identified in the search were also searched for relevant information. Controlled trials (randomized and nonrandomized) were included. To be eligible trials had to compare the effects of outdoor exercise initiatives with those conducted indoors and report on at least one physical or mental wellbeing outcome in adults or children. Screening of articles for inclusion, data extraction, and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Due to the heterogeneity of identified studies a narrative synthesis was performed. Eleven trials (833 adults) were included. Most participants (6 trials; 523 adults) were young students. Study entry criteria and methods were sparsely reported. All interventions consisted of a single episode of walking or running indoors with the same activity at a similar level conducted outdoors on a separate occasion. A total of 13 different outcome measures were used to evaluate the effects of exercise on mental wellbeing, and 4 outcome measures were used to assess attitude to exercise. Most trials (n = 9) showed some improvement in mental wellbeing on one or other of the outcome measures. Compared with exercising indoors, exercising in natural environments was associated with greater feelings of revitalization and positive engagement, decreases in tension, confusion, anger, and depression, and increased energy. However, the results suggested that feelings of calmness may be decreased following outdoor exercise. Participants reported greater enjoyment and satisfaction with outdoor activity and declared a greater intent to repeat the activity at a later date. None of the identified studies measured the effects of physical activity on physical wellbeing or the effect of natural environments on exercise adherence. The hypothesis that there are added beneficial effects to be gained from performing physical activity outdoors in natural environments is very appealing and has generated considerable interest. This review has shown some promising effects on self-reported mental wellbeing immediately following exercise in nature which are not seen following the same exercise indoors. However, the interpretation and extrapolation of these findings is hampered by the poor methodological quality of the available evidence and the heterogeneity of outcome measures employed. The review demonstrates the paucity of high quality evidence on which to base recommendations and reveals an undoubted need for further research in this area. Large, well designed, longer term trials in populations who might benefit most from the potential advantages of outdoor exercise are needed to fully elucidate the effects on mental and physical wellbeing. The influence of these effects on the sustainability of physical activity initiatives also awaits investigation.

Complementary therapies for back pain: is the evidence getting stronger?

Back pain is the most common reason for using complementary therapies. This analysis of the trial evidence is aimed at determining whether the evidence base for or against complementary therapies for back pain is getting stronger. Two series of systematic reviews conducted with the same methodology 5 years apart were compared. The results suggest that the weight of the evidence has increased between 2000 and 2005 for a number of interventions. The direction of the evidence, however, remained unchanged for all but one therapy. We conclude that the value of complementary therapies in the management of back pain remains encouraging but not fully convincing.

Acupuncture: its evidence-base is changing.

The effectiveness of acupuncture remains a controversial issue. The aim of this article is to evaluate trends over time in the development of the evidence-base of acupuncture. A comparison of two series of systematic reviews was conducted. The first related to the evidence-base in 2000, the second related to 2005. Both employed virtually the same methodology and criteria for evaluation. The results indicate that the evidence base has increased for 13 of the 26 conditions included in this comparison. For 7 indications it has become more positive (i.e. favoring acupuncture) and for 6 it had changed in the opposite direction. It is concluded, that acupuncture research is active. The emerging clinical evidence seems to imply that acupuncture is effective for some but not all conditions.

Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations.

A double-blind crossover comparison was made in 18 nonedematous hypertensive subjects with glomerular filtration rates exceeding 70 ml/min/1.73 m2 of the effects of 5 mg metolazone and 5 mg bendroflumethiazide on blood pressure and metabolic parameters. After a 4-wk run-in placebo period, patients received either metolazone or bendroflumethiazide for 6 wk in a crossover fashion with an intervening washout period of 4 wk. Metolazone induced a more sustained and greater blood pressure response than bendroflumethiazide. Changes in plasma potassium, urate, bicarbonate, renin, and angiotensin II occurred during treatment with both metolazone and bendroflumethiazide; the only significant difference, however, was in changes in plasma bicarbonate. Total body potassium (TBK), measured by whole-body monitor, did not fall outside the normal range with either metolazone or bendroflumethiazide, although metolazone induced a greater reduction in TBK (6.2 gm, 5.5% of TBK) than bendroflumethiazide (1.2 gm, 1.1% of TBK, p < 0.05). Our results suggest that metolazone is a more effective antihypertensive and induces similar but greater metabolic changes than bendroflumethiazide. The results of our comparison suggest that although changes in plasma potassium and TBK are minor, they are greater with metolazone, and potassium supplements may not be necessary in nonedematous hypertensive patients with normal renal function.

Body elemental composition, with particular reference to total and exchangeable sodium and potassium and total chlorine, in untreated and treated primary hyperaldosteronism.

The whole body content of sodium, potassium, chlorine, calcium, phosphorus and nitrogen was measured by neutron activation analysis in 13 patients with untreated primary hyperaldosteronism (Conn's syndrome; aldosterone-secreting adenoma). Concurrently, exchangeable sodium and potassium were estimated by isotope dilution. Results were compared with values in the same patients during treatment with potassium-conserving diuretics and again after removal of the adenoma; and also with those in a series of 30 patients having untreated essential hypertension. Both total body and exchangeable sodium were high in Conn's syndrome before treatment and were reduced by spironolactone or amiloride and by subsequent surgery. There was no evidence of alteration in the proportion of non-exchangeable sodium in this disease, in contrast to earlier reports. Total body and exchangeable potassium were low in untreated Conn's syndrome and increased to normal after therapy: the proportion of non-exchangeable potassium was similar before and after treatment, and also similar to that in essential hypertension. Total body chlorine was increased before treatment in Conn's syndrome and returned to normal with therapy; body calcium, phosphorus and nitrogen were normal throughout.

The effects of pentobarbitone and pethidine on foetal breathing movements in sheep.

1 Small doses of pentobarbitone (4 mg/kg i.v.) administered to sheep in the last third of pregancy had little overt effect on the mothers. In the foetus they caused arrest of breathing movements, an alteration in the character of the electrocorticogram and cardiovascular changes which varied with gestational age. 2 In contrast, relatively large doses of pethidine (100-200 mg) admininstered to the mother had no consistent effect on normal foetal breathing movements, though they abolished the foetal response to hypercapnia. 3 The results are discussed in relation to feotal sleep state.

Changes in the concentration of adrenocorticotrophin and corticosteroid in the plasma of foetal sheep in the latter half of pregnancy and during labour.

The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117+/-19 (S.E.M.) pg/ml which rose to a mean of 286+/-63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64+/-9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma.

Developmental changes in the responses of the adrenal glands of foetal sheep to endogenous adrenocorticotrophin, as indicated by hormone responses to hypoxaemia.

The change in plasma ACTH and corticosteroid concentrations in response to a 60 min period of hypoxaemia were studied in foetal and adult sheep during the latter half of pregnancy. Hypoxaemia consistently caused large rises in the concentration of ACTH in foetal plasma, the magnitude of which did not change with gestational age but was related to the physiological state of the foetus. Before 139 days small and slow rises in corticosteroid (predominantly cortisol) concentration in foetal plasma were observed during hypoxaemia, and these may have been of maternal origin. After 139 days, hypoxaemia caused a rapid and large rise in the concentration of cortisol and corticosterone in foetal plasma, which was largely of foetal origin. Hypoxaemia caused no consistent change in maternal plasma ACTH concentration but was associated with progressive increases in plasma cortisol concentrations. The cortisol: corticosterone ratio in foetal plasma was 1-5 before 139 days and increased to 4-1 several days before term which was lower than the value of 9 in maternal plasma. Small concentrations of 11-deoxycortisol and cortisone were detected in maternal and foetal plasma, the changes of which were small during hypoxaemia. The results indicate that a maturational change in the sensitivity of the foetal adrenal to endogenous ACTH occurs several days before term.

The relation of total body potassium to height, weight, and age in normal adults.

Total body potassium was measured in 103 healthy adults using a shadow-shield whole-body monitor of high sensitivity. The range of height was 147 to 192 cm, of weight 43 to 92 kg, and of age 18 to 77 years. The values obtained for total body potassium were correlated with height, with weight, and with height and weight. Age was then included as an additional variable. The standard deviation from regression was smaller when total body potassium was correlated with height than with weight and was further reduced, to about 9%, in a multiple regression using height and age. The advantages of this relationship over indices involving weight are discussed. The smallest standard deviation from regression, 7.5%, was obtained when total body potassium was correlated with height, weight, and age. The usefulness of this relationship is discussed with comment on its limitations.A regression equation was derived between lean body mass (derived from height and weight) and total body potassium with a standard deviation from regression of 5.5% in males and 7.3% in females.

Fasting hyperinsulinemic hypoglycemia after ritodrine therapy for premature labor.

A 26-year-old woman with a triplet pregnancy was treated prophylactically with ritodrine beginning at 15 weeks' gestation. At 32 weeks, she was admitted in preterm labor, and over the next 12 days received high-dose oral or intravenous ritodrine. Three female infants were delivered by cesarean section after spontaneous rupture of the membranes. Postoperatively, she developed profound hypoglycemia with inappropriately high insulin levels. Maternal hypoglycemia after ritodrine therapy in pregnancy has not been reported previously. We discuss possible mechanisms.

Whole body calcium deficit in cadmium-exposed workers with hypercalciuria.

Whole body elemental composition of 15 men occupationally exposed to cadmium was determined by total body in vivo neutron activation analysis and whole body counting. A significant deficit (P less than 0.01) in calcium was observed, compared with two groups of control subjects. The deficit increased with length of time exposed to cadmium.

Measurement of calcium in sections of a human skeleton using a reactor spectrum-in vivo activation analysis technique.

Factors influencing the precision of measuring changes in the calcium content of sections of bone, including vertebrae, using reactor neutrons for partial body in vivo activation analysis have been examined and quantified. These factors include (a) the choice of incidient neutron spectrum, (b) the uniformity of activation with depth in the body, (c) reproducibility, (d) interfering reactions, (e) sensitivity and (f) dosimetry. It is concluded that an overall precision of 2.8%-3.2% (coefficient of variation) can be attained with a neutron dose of 50 mrad or 3-4% with a dose as low as 20 mrad.

Intercomparison of whole-body counters using a multinuclide calibration phantom.

Whole-body counters in the UK have been compared using a multinuclide anthropomorphic phantom. A standard Bush phantom was modified by inserting channels into the long axis of each section. Radionuclide sources sealed in a urea-formaldehyde polymer were then inserted into the channels to simulate distributions of radioactivity in a human. The phantom was taken to 10 whole-body counters in the UK and estimates of 134Cs, 137Cs and 40K were obtained both separately and as mixtures. Results showed close agreement between the median estimates and the known activities. The technique also allowed diagnosis of particular problems in calibration for several of the counters.

A two-way scanning method for total body in vivo neutron activation analysis.

When determining the total body content of many elements by neutron activation analysis, irradiation and whole body counting by scanning along the length of the body has significant advantages. A neutron source of lower output and a whole body counter using smaller detectors and shielding (than otherwise needed) can provide a high, uniform response for many elements throughout the body. This was previously achieved by making the speed and direction of scanning identical in irradiation and counting (one-way scanning). A simple theoretical model for scanned irradiation and counting is described. The model is used to show that a scanning regime in which both scanning directions are used (two-way scanning) can provide acceptably uniform response for elements having induced activities of a wide range of half-life. This is supported by measurements made using an existing scanning facility for total body in vivo neutron activation analysis. The two-way scanning regime offers the advantages of increased patient comfort, simpler operation and more efficient use of the time available for counting induced activity.

Calibration and evaluation of a system of total body in vivo activation analysis using 14 MeV neutrons.

A system has been established for determining the total body contents of calcium, phosphorus, sodium, chlorine and nitrogen by neutron activation analysis using sealed-tube neutron generators and a shadow-shield whole-body counter. The system was calibrated using three anthropomorphic phantoms of different sizes, filled with various mixtures of the activatable elements in amounts similar to those in man. The reproducibility determined from replicate measurements, was on average +/- 2.9% (SD). The average uncertainty in absolute measurements was estimated to be +/- 4.2% (68% confidence interval).

Neutron uniformity studies related to clinical total body in vivo neutron activation analysis.

Methods of assessing the uniformity of thermal and fast neutron fluence in relation to total body in vivo neutron activation analysis are described. Results are presented for 14 MeV neutrons emitted by sealed tube generators housed in a massive concrete shield, representing a substantial source of neutrons degraded in energy. Optimisation of conditions for patient irradiations is discussed and it is shown that acceptable uniformity of fluence can be achieved with little or no premoderation of the incident neutrons.

Reliability of absolute and relative measurement of total body nitrogen by the 14N(n, 2n)13N reaction.

Measurements of total body nitrogen by in vivo neutron activation analysis using the 14N(n, 2n)13N reaction, may conveniently be calibrated using phantoms in which nitrogen is uniformly distributed. However, the response of the method varies considerably in the thickest body sections and in order to validate the calibration, it is necessary also to consider the spatial distributions both of nitrogen and of the major interfering element, oxygen. The effects of these spatial distributions have been calculated for the experimental conditions obtained at the East Kilbride facility for total body in vivo neutron activation analysis. The response for total body nitrogen was found to depend strongly on body weight (in the rang e 40 to 100 kg) but only weakly on total body content of adipose tissue (0 to 65% of body weight). It differed little from the response calculated for the nitrogen distributed uniformly within the body. The calculation was tested successfully against measured changes in the net response for nitrogen resulting from 'homogenisation' of inhomogeneous phantoms.