Cosmology and fundamental physics with the ELT-ANDES spectrograph.

State-of-the-art 19th century spectroscopy led to the discovery of quantum mechanics, and 20th century spectroscopy led to the confirmation of quantum electrodynamics. State-of-the-art 21st century astrophysical spectrographs, especially ANDES at ESO's ELT, have another opportunity to play a key role in the search for, and characterization of, the new physics which is known to be out there, waiting to be discovered. We rely on detailed simulations and forecast techniques to discuss four important examples of this point: big bang nucleosynthesis, the evolution of the cosmic microwave background temperature, tests of the universality of physical laws, and a real-time model-independent mapping of the expansion history of the universe (also known as the redshift drift). The last two are among the flagship science drivers for the ELT. We also highlight what is required for the ESO community to be able to play a meaningful role in 2030s fundamental cosmology and show that, even if ANDES only provides null results, such 'minimum guaranteed science' will be in the form of constraints on key cosmological paradigms: these are independent from, and can be competitive with, those obtained from traditional cosmological probes.

The Hubble constant troubled by dark matter in non-standard cosmologies.

The Standard Cosmological Model has experienced tremendous success at reproducing observational data by assuming a universe dominated by a cosmological constant and dark matter in a flat geometry. However, several studies, based on local measurements, indicate that the universe is expanding too fast, in disagreement with the Cosmic Microwave Background. Taking into account combined data from CMB, Baryon Acoustic Oscillation, and type Ia Supernovae, we show that if the mechanism behind the production of dark matter particles has at least a small non-thermal origin, one can induce larger values of the Hubble rate [Formula: see text], within the [Formula: see text]CDM, to alleviate the trouble with [Formula: see text]. In the presence of non-standard cosmology, however, we can fully reconcile CMB and local measurements and reach [Formula: see text]-74 [Formula: see text].

Increased eutrophication and nutrient imbalances in the agricultural soil of NE Catalonia, Spain.

The soil C, N, P and K content of agricultural soil were measured over the last 4 decades in NE Catalonia (NE Spain). Plant-available P and K increased by ca 109 and 105% respectively and total N decreased by 30%. The increases in plant-available P content are in accordance with the increasingly used pig slurry being very rich in P, and with P tendency to be retained in soils, since it is less mobile than N. The total soil N (N(tot)) decrease occurred in the first decade (by 41%). The uptake and withdrawal of mineral N by crops and the leaching of mineral N into groundwater and rivers after torrential rainfalls were the two likely major pathways of N-loss from the soil. After the first decade, there has been no further decrease of N(tot) as a result of the increasing fertilization of these fields, including the increasing applications of pig slurry. These results show an increasing P eutrophication in Mediterranean agricultural soils and will have several consequences for the next decades with (i) an increasing unbalance between N and P (and K) in soils that might affect crop productivity (ii) an increasing leaching of N as nitrate to continental waters, both ground and surface waters, and (iii) a consequent need for the establishment of another fertilization strategy based on lowering the use of pig slurry and on increasing the use of fertilizers of slow mineralization that increase soil organic matter, and stabilise the soil N and P contents.

Differences on nitrogen availability in a soil amended with fresh, composted and thermally-dried sewage sludge.

Anaerobically-digested sludge called fresh sludge (F), composted sludge (C) and thermally-drying sludge (T), all from the same batch, were applied to the surface of a calcareous Udic Calciustept with loamy texture. Dosage equivalent was 10 t ha(-1) of dry matter. The concentration of mineral nitrogen (ammonium and nitrate) in the soil was measured in order to estimate the effects of the post-treatments to which the different kinds of sewage sludge are subjected in relation to the availability of N in the surface layer of the soil. The most significant differences in NH(4)-N and NO(3)-N concentrations due to the transformation of the organic matter were observed during the first three weeks following soil amendment. Thermally-dried and composted sludge initially displayed higher concentrations of ammonium and nitrate in soil. Five months after the amendment, soil applied with fresh sludge showed the highest concentrations of NH(4)-N and NO(3)-N (6.1 and 36.6 mg kg(-1), respectively). It is clear that the processes of composting and thermal-drying influence the bioavailability of nitrogen from the different types of sewage sludge.

Toxic effects of digested, composted and thermally-dried sewage sludge on three plants.

In order to evaluate potential toxic effects of stabilized sewage sludge that are currently applied to agricultural soils, three types of municipal sewage sludge and one pig slurry were subjected to phytotoxicity assays using three plants (Brassica rapa, Lolium perenne and Trifolium pratense). Equivalent batches of aerobically and anaerobically-digested sludge (F) from two municipal wastewater treatment plants, were composted (C) or thermally dried (T). In addition, one anaerobically-digested and thermally-dried pig slurry (P) was tested. A seedling growth test was performed in accordance with the OECD Guideline 208A, using seed emergence and shoot length as endpoints to identify the inhibition of plants growing in increasing doses of sludge. A correlation analysis between EC50 and physico-chemical parameters or the pollutant burden of the biosolids was also calculated. In all tests, lower germination rates were observed for T. pratense than for L. perenne and B. rapa. A moderate stimulatory effect on shoot length at low doses was observed for the three plants. In these wastes, a strong positive correlation was found between higher values of EC50 (less toxicity) and the stability degree of their organic matter, and a negative correlation between EC50 and total N, hydrolysable N or NH4-N content. No correlations were found with heavy metal or organic pollutant content in those wastes. Results indicate that digested sludge, thermally-dried sludge and thermally-dried pig slurry have non-negligible short term phytotoxic effects, and confirm that composting is an effective sludge treatment for the reduction of phytotoxicity.

Functional Results of Renal Preservation in Hypothermic Pulsatile Machine Perfusion Versus Cold Preservation: Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Hypothermic pulsatile machine perfusion (HPMP) decreases the rate of delayed graft function (DGF) in kidney grafts, compared with cold storage. However, it is not clear its use in the different subgroups of grafts. The objective was to review systematically all studies with better methodologic quality that compare HPMP versus cold storage. METHODS: A systematic review was performed. The sources were Pubmed, Pubmed Central, Cochrane Library, Clinical Key, and Ovid. All randomized controlled trials that compared HPMP versus cold storage in renal grafts from human donors were considered. Outcomes analyzed were: percentage of DGF, primary nonfunction (PNF), and graft function in each group and for the different types of grafts, brain-death donors (DBDs), and different subgroups of donors after circulatory death (DCDs). RESULTS: Twelve clinical trials, out of 9,867 titles, were included. HPMP improved DGF overall, as well as in DBDs and DCDs. The relative risks [RRs] were 0.79 (95% CI, 0.71-0.88), 0.85 (95% CI, 0.74-0.98), and 0.75 (95% CI, 0.61-0.92), respectively. There were no differences in PNF overall and for DBDs or DCDs. The RRs were 0.92 (95% CI, 0.73-1.16), 0.78 (95% CI, 0.22-2.73), and 1.13 (95% CI, 0.73-1.77), respectively. However, analysis with the better quality studies, overall RR for PNF was 0.62 (95% CI, 0.39-0.96). There were no differences between the graft function at 3 months after transplantation. CONCLUSIONS: HPMP moderately improved the DGF results in grafts from cadaver donors of all types. HPMP could improve the PNF in grafts from DBDs, although more clinical trials are needed to prove that.

Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial.

OBJECTIVE: Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN: We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS: A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS: We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS: A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS: Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.

Nonextensive models for earthquakes.

We have revisited the fragment-asperity interaction model recently introduced by Sotolongo-Costa and Posadas [Phy. Rev. Lett. 92, 048501 (2004)] by considering a different definition for mean values in the context of Tsallis nonextensive statistics and introducing a scale between the earthquake energy and the size of fragment epsilon proportional to r3. The energy-distribution function (EDF) deduced in our approach is considerably different from the one obtained in the above reference. We have also tested the viability of this EDF with data from two different catalogs (in three different areas), namely, the NEIC and the Bulletin Seismic of the Revista Brasileira de Geofísica. Although both approaches provide very similar values for the nonextensive parameter , other physical quantities, e.g., energy density, differ considerably by several orders of magnitude.

Bioaccumulation of heavy metals in Dactylis glomerata L. growing in a calcareous soil amended with sewage sludge.

The total and DTPA-extractable concentrations of Pb, Ni, Zn, Cu, Cr and Cd were measured in a calcareous soil amended with different doses of sewage sludge under field conditions. The same metals were also measured in the roots and leaves of Dactylis glomerata at the end of the first vegetative period after the sludge was added. The root concentrations of all the metals were unrelated to their concentrations in the soil. Leaf concentrations of Zn and Cr correlated with total (Zn) and DTPA-extractable (Zn and Cr) concentrations in the soil. DTPA extraction did not appear to be very useful for evaluating the bioavailability of metals in this kind of soil as it gave very low correlation coefficients with leaf content (r = 0.684, P = 0.0049 for Zn and r = 0.557, P = 0.0249 for Cr). Concentrations of Pb, Ni, Cu, and Cd in roots and leaves of Dactylis glomerata were unrelated to the total or DTPA-extractable concentrations in the sludge-amended soil.

[The use of ureteral stents and catheters in renal transplantation.] / Empleo de catéteres y stents ureterales en el trasplante renal.

Mayor urological complications, fistulae and stenosis, mainly affect the vesicoureteral anastomosis and present in the early post-transplant period. The systematic use of ureteral catheters keeps selecbeing controversial with many groups using them only selectively depending on the existence of pretransplant or intraoperative risk factors. METHODS: We performed a bibliographic review through automatized search in the Medline bibliographic database, as the main bibliographic source, and also in Clinical Key. The search strategy included the following terms: "stent" AND "kidney transplantation". RESULTS: The bibliographic search revealed the protective effect of the use of ureteral catheters in the transplant ureteroneocystostomy for both development of fistulae (RR 0.29, 0.12 to 0.74, p=0.009) and stenosis (RR 0.27, 0.09 to 0.81, p=0.02). The use of catheters in immunosuppressed patients was associated with significant increase of the incidence of post-transplant urinary tract infections (RR 1.49 IC 95% 1.04 to 2.15, p=0.03) that was prevented by antibiotic prophylaxis with cotrimoxazole directed against pneumocistis carinii. The rates of permeability of self-expandable metallic stents and extra-anatomic bypasses in the treatment of ureteral stenosis after renal transplantation in high surgical risk patients or after the failure of previous surgery, has varied from 50% to 100%, with a limited number of patients included. CONCLUSIONS: The use of ureteral catheters in the extravesical ureteroneocystostomy reduces the incidence of anastomotic complications. Surgery is the treatment of choice of post-transplant ureteral stenosis. The use of metallic stents and extra-anatomic bypasses should be limited to complex ureteral stenosis when primary therapy has failed, in high surgical risk patients or chronic graft dysfunction.

GH secretion in two siblings with Laron's dwarfism: the effects of glucose, arginine, somatostatin, and bromocryptine.

The secretion of GH in two siblings with clinical dwarfism and high GH plasma levels (the mean of several basal values; 233.83 ng/ml in patient A and 178.16 in patient B has been studied with several dynamic tests. An arginine infusion increased GH levels in both cases (+193.55% for A, +140.27% for B). No significant modifications were obtained with oral glucose tolerance test +18.70% for A, +24.32% for B). A bolus of somatostatin almost completely prevented the rise in GH levels in response to arginine. Pretreatment with bromocryptine clearly increased basal GH plasma levels (A, +58.66%; B, +56.03%) and the response to arginine. As in the case of a normal hypothalamus, the hypothalamus of Laron's syndrome responds to arginine and bromocryptine, with GH elevations. Somatostatin suppresses GH levels. A lack of response to glucose can be considered as a nonspecific effect of the very low biological activity of the stimulus in a hyperstimulated hypothalamus. We suggest that GH secretion by the hypothalmo pituitary system in Laron's syndrome is normal, and that GH hyperproduction may be due to a generalized defect in GH receptors or to the low levels of somatomedin.

Serum growth hormone-binding protein is unchanged in adult panhypopituitarism.

The role of GH in regulating GH-binding protein (GHBP) and GH receptor concentrations in humans is not clear. Studies performed mostly in children and on a minor scale in adults are somewhat controversial. The key question as to whether GHBP levels are altered in hypopituitarism before GH treatment is instituted remains unanswered. In this study, we have selected a severely GH-deficient group of adult patients with panhypopituitarism, acquired as a result of surgery and irradiation of hypothalamic-pituitary tumors, to evaluate the GHBP/receptor status by measuring GHBP activity in plasma. Twenty panhypopituitary patients (8 males and 12 females; age range, 20-74 yr) and 20 age (22-68 yr)- and sex-matched normal subjects were studied. GH deficiency was confirmed by insulin-induced hypoglycemia and arginine infusion tests; the peak GH response was less than 2 micrograms/L. Plasma insulin-like growth factor-I levels were below or in the low normal range (mean +/- SD, 88.3 +/- 53.6 micrograms/L) and were significantly different from insulin-like growth factor-I (IGF-I) levels in the normal group (mean +/- SD, 189 +/- 49.8 micrograms/L; P < 0.01). Plasma GHBP activity, measured using a GH-binding/gel chromatography assay, showed similar values in the GH-deficient group (mean +/- SD, 14.1 +/- 3.83%) and the control group (mean +/- SD, 13.7 +/- 3.79%), with no statistically significant difference. Neither the intra- nor intergroup comparison of GHBP levels according to age and sex showed statistically significant differences or age trends. In the light of these data and considering that GHBP activity in plasma probably reflects the GH receptor status in tissues, we may assume that the GH receptor was unaffected by chronic GH deficiency. These findings also support the previously reported concept that the GHBP/receptor level is a relatively fixed determinant of growth, established individually and independently of GH secretory status in early life, perhaps on a genetic basis.

Prolactin and deficient luteal function.

The possibility of prolactin-dependent subfertility was investigated in a group of 8 women, with luteal insufficiency exhibiting moderately elevated plasma prolactin (PRL) levels and/or galactorrhea. Another group of 10 normal women volunteers served as the control group. A "luteal index" was elaborated by integration of the area below the curve of plasma progesterone (P) values recorded throughout the postovulatory period. The calculated index for normal women was 177 +/- 35 (SD) expressed as [(ng/ml) x time], and the value of 107 (--2 SD) was adopted as the lower limit of normality (97.5% confidence limit). All 8 patients had luteal indexes (range 20--105) below the established limit. Therapy with bromocriptine (CB 154), 5 mg/day, suppressed PRL to normal levels and prolonged the postovulatory hyperthermic phase in 6 out of 8 women. This was accompanied by an improvement in the luteal index, and 5 women conceived. It is concluded that prolactin may interfere with normal progesterone synthesis by the corpus luteum, as demonstrated by the prompt restoration of fertility by bromocriptine treatment in women with regular cycles and inadequate luteal function.

Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201-995 before transsphenoidal surgery.

The purpose of this study was to determine whether the long-acting somatostatin analog SMS 201-995 (octreotide) shrinks growth hormone (GH)-secreting adenomas and improves the results of subsequent transsphenoidal surgery. Ten previously untreated active acromegalic patients (nine women and one man) with invasive tumors were treated with SMS 201-995 (100 micrograms subcutaneously every 8 hours) for 6 weeks prior to transsphenoidal surgery. The clinical activity, mean GH secretion, insulin-like growth factor (IGF)-I concentration, and tumor volume were measured under basal conditions and on Days 14, 28, and 42 of treatment. The SMS 201-995 improved the symptoms of acromegaly in all patients. Mean levels of both GH and IGF-I (+/- standard deviation) were significantly decreased by Day 14 (from 92.9 +/- 30.5 to 44.9 +/- 20.3 micrograms/liter and from 10.6 +/- 7.4 to 5.9 +/- 2.6 U/ml, respectively), after which there were only slight further decreases. Six (60%) of the 10 patients experienced tumor shrinkage ranging from 9% to 78% (mean 30%). When it occurred, tumor shrinkage was significant by Day 14 (7.9 +/- 6.3 to 6.5 +/- 5.1 cu cm) and no further shrinkage was achieved by longer administration. Transsphenoidal surgery reduced postoperative GH levels to less than 2 micrograms/liter and IGF-I to less than 1.5 U/ml in six patients (60%). This percentage of cure is higher than expected from the literature and the authors' previous experience. However, an investigation of the influence of this drug on several parameters, such as reduction of tumor size or GH and IGF-I concentrations, has failed to prove any relationship. Only pretreatment size of the tumor was of predictive value with respect to the surgical outcome.

Performance of industrial strains of Saccharomyces cerevisae during wine fermentation is affected by manipulation strategies based on sporulation.

Genetic manipulation of industrial wine yeast strains has become an essential tool for both the study of the molecular mechanisms underlaying their physiology and the improvement of their fermentative properties. The construction of null mutants for any gene in these usually diploid strains, by using a procedure based on sporulation of a heterozygote lacking one copy of the gene of interest, has been tested as an alternative to the tedious work of sequential disruption of the complete set of copies. Our results indicate that most of the homozygotes resulting from sporulation of wine yeast strains are defective in glucose consumption under microvinification conditions in synthetic must and produce stuck fermentations. These kinds of defects are observed even for strains derived from sporulation of wild type. Alteration of genomic features of wine strains by sporulation is responsible for these defects.

[Acute pancreatitis and malabsorption with tetany secondary to Crohn's disease with duodenal involvement]. / Pancreatitis aguda y malabsorción con tetania secundarias a enfermedad de Crohn con afectación duodenal.

Involvement of the duodenum in Crohn's disease is uncommon, and the pathomechanism of the associated acute pancreatitis remains controversial. We describe a case of Crohn's disease with duodenal involvement associated with hyperamylasemia and malabsorption showing a favorable response to steroid treatment.

[Advanced cancer of the rectum and pregnancy. Review of the literature apropos of a case]. / Cancer avancé du rectum et grossesse. Revue de la littérature à propos d'un cas.

The authors report a case of advanced rectal cancer in a pregnant woman of 30 years of age. It was a glandular adenocarcinoma discovered in the second trimester of pregnancy. The clinical picture was one of rectal bleeding with digestive disturbances. The patient had a caesarean operation at 29 weeks of amenorrhoea because of a change in her general state. Post-operatively palliative chemotherapy was started. The patient died on the 13th day.

Trivalent arsenic species induce changes in expression and levels of proinflammatory cytokines in intestinal epithelial cells.

Chronic arsenic (As) toxicity in humans has been documented in many countries where exposure mostly occurs through drinking water. The As immunotoxic effects have been demonstrated in animal models as well as in humans. The studies of the immunotoxicity of As have centered on organs related to immune response or target organs, with few data being available at intestinal level. The present study has evaluated the changes in the expression and release of cytokines in Caco-2 cells, widely used as an intestinal epithelial model. Differentiated cells were exposed to 1 µM of As(III), 0.1 µM of monomethylarsonous acid [MMA(III)] and 1 µM of dimethylarsinous acid [DMA(III)] during 2, 4, 6 and 24 h. Additionally, the effect of As coexposure with lipopolysaccharide (LPS, 10 ng/mL) has been evaluated. The results show trivalent species to induce increases in the expression and release of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), IL6, IL8 - the magnitude and time of response being different for each As species. The response of greatest magnitude corresponds to DMA(III), followed by As(III), while MMA(III) generates a limited response. Furthermore, the presence of LPS in the co-exposed cells could affect the expression and secretion of cytokines compared with individual exposure to arsenicals, especially for As(III)/LPS and DMA(III)/LPS.