Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

Prediction of sediments toxicity using consensus-based sediment quality guidelines and benthic foraminifera in the Ria de Aveiro(Portugal)

Ria de Aveiro is a large and shallow lagoon on the west coast of Portugal (40º38’N, 8º45´W), characterized by a complex geometry. It includes large areas of intertidal flats and a network of narrow channels which are connected to the Atlantic by an artificial inlet. Tides are the main forcing of the hydrology and physical processes of the lagoon. The deeper areas near the inlet are characterized by strong marine influence through tidal inflow, with high values of current velocity (>1m/s) and tidal range (2–3 m at spring tides), while in remote shallow areas, the circulation and the sea water inflow are reduced. These remote areas are more influenced by fresh waters received from several rivers and several small streams. The Aveiro lagoon is a very important ecosystem but as been used as recipient for various kinds of anthropogenic wastes resulting from the high population density, urban activities and industrial development. One of the most important Portuguese industrial centre is located in the lagoon margins. Ria de Aveiro is a coastal lagoon under huge direct antropization. This system also suffers strong diffuse antropization. This work is related with diffuse antropization linked with chemical pollution which may lead to biological stress and collapse.

A study of air-sea interaction processes on water mass formation and upwelling in the Mediterranean sea

Air-sea interactions are a key process in the forcing of the ocean circulation and the climate. Water Mass Formation is a phenomenon related to extreme air-sea exchanges and heavy heat losses by the water column, being capable to transfer water properties from the surface to great depth and constituting a fundamental component of the thermohaline circulation of the ocean. Wind-driven Coastal Upwelling, on the other hand, is capable to induce intense heat gain in the water column, making this phenomenon important for climate change; further, it can have a noticeable influence on many biological pelagic ecosystems mechanisms. To study some of the fundamental characteristics of Water Mass Formation and Coastal Upwelling phenomena in the Mediterranean Sea, physical reanalysis obtained from the Mediterranean Forecating System model have been used for the period ranging from 1987 to 2012. The first chapter of this dissertation gives the basic description of the Mediterranean Sea circulation, the MFS model implementation, and the air-sea interaction physics. In the second chapter, the problem of Water Mass Formation in the Mediterranean Sea is approached, also performing ad-hoc numerical simulations to study heat balance components. The third chapter considers the study of Mediterranean Coastal Upwelling in some particular areas (Sicily, Gulf of Lion, Aegean Sea) of the Mediterranean Basin, together with the introduction of a new Upwelling Index to characterize and predict upwelling features using only surface estimates of air-sea fluxes. Our conclusions are that latent heat flux is the driving air-sea heat balance component in the Water Mass Formation phenomenon, while sensible heat exchanges are fundamental in Coastal Upwelling process. It is shown that our upwelling index is capable to reproduce the vertical velocity patterns in Coastal Upwelling areas. Nondimensional Marshall numbers evaluations for the open-ocean convection process in the Gulf of Lion show that it is a fully turbulent, three-dimensional phenomenon.

Genetics of GHRH, GHRH-receptor, GH and GH-receptor: its impact on pharmacogenetics

When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required and, appropriate consideration should be given to genetic defects causing GH deficiency (GHD). Because Insulin-like-Growth Factor-I (IGF-I) plays a pivotal role, GHD could also be considered as a form of IGF-I deficiency (IGFD). Although IGFD can develop at any level of the GHRH-GH-IGF axis, a differentiation should be made between GHD (absent to low GH in circulation) and IGFD (normal to high GH in circulation). The main focus of this review is on the GH-gene, the various gene alterations and their possible impact on the pituitary gland. However, although transcription factors regulating the pituitary gland development may cause multiple pituitary hormone deficiency they may present initially as GHD. These defects are discussed in various different chapters within this book, whereas, the impact of alterations of the GHRH-, GHRH-receptor- --as well as the GH-receptor (GHR) gene--will be discussed here.

National institutes of health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke

Background and Purpose—There is some controversy on the association of the National Institutes of Health Stroke Scale (NIHSS) score to predict arterial occlusion on MR arteriography and CT arteriography in acute stroke. Methods—We analyzed NIHSS scores and arteriographic findings in 2152 patients (35.4% women, mean age 66±14 years) with acute anterior or posterior circulation strokes. Results—The study included 1603 patients examined with MR arteriography and 549 with CT arteriography. Of those, 1043 patients (48.5%; median NIHSS score 5, median time to clinical assessment 179 minutes) showed an occlusion, 887 in the anterior (median NIHSS score 7/0–31), and 156 in the posterior circulation (median NIHSS score 3/0–32). Eight hundred sixty visualized occlusions (82.5%) were located centrally (ie, in the basilar, intracranial vertebral, internal carotid artery, or M1/M2 segment of the middle cerebral artery). NIHSS scores turned out to be predictive for any vessel occlusions in the anterior circulation. Best cut-off values within 3 hours after symptom onset were NIHSS scores ≥9 (positive predictive value 86.4%) and NIHSS scores ≥7 within >3 to 6 hours (positive predictive value 84.4%). Patients with central occlusions presenting within 3 hours had NIHSS scores <4 in only 5%. In the posterior circulation and in patients presenting after 6 hours, the predictive value of the NIHSS score for vessel occlusion was poor. Conclusions—There is a significant association of NIHSS scores and vessel occlusions in patients with anterior circulation strokes. This association is best within the first hours after symptom onset. Thereafter and in the posterior circulation the association is poor.

Toward explaining the Holocene carbon dioxide and carbon isotope records: Results from transient ocean carbon cycle-climate simulations

[1] The Bern3D model was applied to quantify the mechanisms of carbon cycle changes during the Holocene (last 11,000 years). We rely on scenarios from the literature to prescribe the evolution of shallow water carbonate deposition and of land carbon inventory changes over the glacial termination (18,000 to 11,000 years ago) and the Holocene and modify these scenarios within uncertainties. Model results are consistent with Holocene records of atmospheric CO2 and δ13C as well as the spatiotemporal evolution of δ13C and carbonate ion concentration in the deep sea. Deposition of shallow water carbonate, carbonate compensation of land uptake during the glacial termination, land carbon uptake and release during the Holocene, and the response of the ocean-sediment system to marine changes during the termination contribute roughly equally to the reconstructed late Holocene pCO2 rise of 20 ppmv. The 5 ppmv early Holocene pCO2 decrease reflects terrestrial uptake largely compensated by carbonate deposition and ocean sediment responses. Additional small contributions arise from Holocene changes in sea surface temperature, ocean circulation, and export productivity. The Holocene pCO2 variations result from the subtle balance of forcings and processes acting on different timescales and partly in opposite direction as well as from memory effects associated with changes occurring during the termination. Different interglacial periods with different forcing histories are thus expected to yield different pCO2 evolutions as documented by ice cores.

Cytokines and pregnancy in rheumatic disease

Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.

Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis

OBJECTIVE: The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis. DESIGN: Random order, cross-over design. SETTING: University laboratory. SUBJECTS: Eight sedated and mechanically ventilated pigs. INTERVENTIONS: Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started. MEASUREMENTS AND MAIN RESULTS: During infusion of epinephrine (0.8 +/- 0.2 mug/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 mug/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 mug/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). CONCLUSIONS: Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.

Myocardial infarction and post-traumatic stress disorder: frequency, outcome, and atherosclerotic mechanisms

BACKGROUND: Post-traumatic stress disorder (PTSD) may develop in the aftermath of an acute myocardial infarction (MI). Whether PTSD is a risk factor for cardiovascular disease (CVD) is elusive. The biological mechanisms linking PTSD with atherosclerosis are unclear. DESIGN: A critical review of 31 studies in the English language pursuing three aims: (i) to estimate the prevalence of PTSD in post-MI patients; (ii) to investigate the association of PTSD with cardiovascular endpoints; and (iii) to search for low-grade systemic inflammatory changes in PTSD pertinent to atherosclerosis. METHODS: We located studies by PubMed electronic library search and through checking the bibliographies of these sources. RESULTS: The weighted prevalence of PTSD after MI was 14.7% (range 0-25%; a total of 13 studies and 827 post-MI patients). Two studies reported a prospective association between PTSD and an increased risk of cardiovascular readmission in post-MI patients and of cardiovascular mortality in combat veterans, respectively. In a total of 11 studies, patients with PTSD had increased rates of physician-rated and self-reported cardiovascular diseases. Various cytokines and C-reactive protein were investigated in a total of seven studies suggesting that PTSD confers a pro-inflammatory state. CONCLUSIONS: Increasing evidence suggests that PTSD specifically related to MI develops considerably frequently in post-MI patients. More research is needed in larger cohorts applying a population design to substantiate findings suggesting PTSD is an atherogenic risk factor and to understand better the suspected behavioural and biological mechanisms involved.

[Arginine-vasopressin in septic and vasodilatorial shock]

Current therapy of septic/vasodilatory cardiovascular failure includes volume resuscitation and infusion of inotropic and vasopressor agents. Norepinephrine is the first-line vasoconstrictor, and can stabilize hemodynamic variables in most patients. Nonetheless, irreversible cardiovascular failure which is resistant to conventional hemodynamic therapies still is the main cause of death in patients with severe sepsis and septic shock. In such advanced, catecholamine-resistant shock states, arginine-vasopressin (AVP) has repeatedly caused an increase in mean arterial blood pressure, a decrease in toxic norepinephrine-dosages, as well as further beneficial hemodynamic, endocrinologic and renal effects. Although AVP exerted negative inotropic effects in previous clinical trials and in selected animal experiments, a continuous low-dose AVP infusion during advanced septic/vasodilatory shock caused a decrease in cardiac index only in patients with a hyperdynamic circulation. Adverse effects on gastrointestinal circulation and the systemic microcirculation can not be excluded, but have not yet been confirmed in clinical prospective trials. Negative side effects of a supplementary AVP therapy are an increase in total bilirubin concentrations, and a decrease in platelet count. A transient increase in hepatic transaminases during AVP infusion is most likely related to preceding hypotensive episodes. Important points which must be considered when using AVP as a "rescue vasopressor" in septic/vasodilatory shock states are: 1) AVP infusion only in advanced shock states that can not be adequately reversed by conventional hemodynamic therapy (e.g. norepinephrine >0,5-0,6 mug/kg/min), 2) presence of normovolemia, 3) AVP infusion only in combination with norepinephrine, 4) strict avoidance of bolus injections and dosages >4 IU/h. Effects of a supplementary AVP infusion in advanced vasodilatory shock on survival are currently examined in a large, prospective multicenter trial in North America and Australia.

The efficacy of non-pharmacological interventions in the management of procedural pain in preterm and term neonates. A systematic literature review

BACKGROUND: Neonates in a neonatal intensive care unit are exposed to a high number of painful procedures. Since repeated and sustained pain can have consequences for the neurological and behaviour-oriented development of the newborn, the greatest attention needs to be paid to systematic pain management in neonatology. Non-pharmacological treatment methods are being increasingly discussed with regard to pain prevention and relief either alone or in combination with pharmacological treatment. AIMS: To identify effective non-pharmacological interventions with regard to procedural pain in neonates. METHODS: A literature search was conducted via the MedLine, CINAHL, Cochrane Library databases and complemented by a handsearch. The literature search covered the period from 1984 to 2004. Data were extracted according to pre-defined criteria by two independent reviewers and methodological quality was assessed. RESULTS: 13 randomised controlled studies and two meta-analyses were taken into consideration with regard to the question of current nursing practice of non-pharmacological pain management methods. The selected interventions were "non-nutritive sucking", "music", "swaddling", "positioning", "olfactory and multisensorial stimulation", "kangaroo care" and "maternal touch". There is evidence that the methods of "non-nutritive sucking", "swaddling" and "facilitated tucking" do have a pain-alleviating effect on neonates. CONCLUSIONS: Some of the non-pharmacological interventions have an evident favourable effect on pulse rate, respiration and oxygen saturation, on the reduction of motor activity, and on the excitation states after invasive measures. However, unambiguous evidence of this still remains to be presented. Further research should emphasise the use of validated pain assessment instruments for the evaluation of the pain-alleviating effect of non-pharmacological interventions.

Exposure dating of Late Glacial and pre-LGM moraines in the Cordon de Doña Rosa, Northern/Central Chile (~ 31°S)

Despite the important role of the Central Andes (15–30° S) for climate reconstruction, knowledge about the Quaternary glaciation is very limited due to the scarcity of organic material for radiocarbon dating. We applied 10Be surface exposure dating (SED) on 22 boulders from moraines in the Cordon de Doña Rosa, Northern/Central Chile (~31° S). The results show that several glacial advances in the southern Central Andes occurred during the Late Glacial between ~14.7±1.5 and 11.6±1.2 ka. A much more extensive glaciation is dated to ~32±3 ka, predating the temperature minimum of the global LGM (Last Glacial Maximum: ~20 ka). Reviewing these results in the paleoclimatic context, we conclude that the Late Glacial advances were most likely caused by an intensification of the tropical circulation and a corresponding increase in summer precipitation. High-latitude temperatures minima, e.g. the Younger Dryas (YD) and the Antarctic Cold Reversal (ACR) may have triggered individual advances, but current systematic exposure age uncertainties limit precise correlations. The absence of LGM moraines indicates that moisture advection was too limited to allow significant glacial advances at ~20 ka. The tropical circulation was less intensive despite the maximum in austral summer insolation. Winter precipitation was apparently also insufficient, although pollen and marine studies indicate a northward shift of the westerlies at that time. The dominant pre-LGM glacial advances in Northern/Central Chile at ~32 ka required lower temperatures and increased precipitation than today. We conclude that the westerlies were more intense and/or shifted equatorward, possibly due to increased snow and ice cover at higher southern latitudes coinciding with a minimum of insolation.

Translocation and cellular entering mechanisms of nanoparticles in the respiratory tract

Anthropogenic nano-sized particles (NSP), ie, particles with a diameter of less than 100 nm, are generated with or without purpose as chemically and physically well-defined materials or as a consequence of combustion processes respectively. Inhalation of NSP occurs on a regular basis due to air pollution and is associated with an increase in respiratory and cardiovascular morbidity and mortality. Manufactured NSP may intentionally be inhaled as pharmaceuticals or unintentionally during production at the workplace. Hence the interactions of NSP with the respiratory tract are currently under intensive investigation. Due to special physicochemical features of NSP, its biological behaviour may differ from that of larger sized particles. Here we review two important themes of current research into the effects of NSP on the lungs: 1) The potential of NSP to cross the blood-air barrier of the lungs, thus gaining access to the circulation and extrapulmonary organs. It is currently accepted that a small fraction of inhaled NSP may translocate to the circulation. The significance of this translocation requires further research. 2) The entering mechanisms of NSP into different cell types. There is evidence that NSP are taken up by cells via well-known pathways of endocytosis but also via different mechanisms not well understood so far. Knowledge of the quantitative relationship between the different entering mechanisms and cellular responses is not yet available but is urgently needed in order to understand the effects of intentionally or unintentionally inhaled NSP on the respiratory tract.

Application and Development Trend of Integrated Supply Chain in China

Importing integrated supply chains have changed Chinese logistic from simplex freight to the process of product of production、circulation and consumption of logistic system. Different modal of integrated supply chain apply in the different companies, bring activity and efficiency integrated supply chain in China. The trend of Chinese integrated supply chain in the future will stress on e-commerce and customer service, and combined Chinese own logistic system to enlarge Chinese logistic, which will more international and world wild.

Igbo Nationalism and Biafra

When I was living in Igboland in 1993 and from 1994 to 1996, there was not much talk about Biafra, the secessionist republic that had been defeated by the Nigerian army in 1970. Not one Igbo politician suggested that his or her people in the southeast of Nigeria should secede again and proclaim a second Biafra. Since 1984, Nigeria had been ruled by the military, and political hopes focused on a return to democracy. Democracy did come in 1999, but it proved a big disappointment. It did not end the marginalisation of the Igbo but led to an increase in the number of ethnic and religious clashes, with Igbo 'migrants' in northern Nigeria as the main victims. It was Nigeria's fourth transition to democracy, and the Igbo lost out again. When I returned to Igboland for brief visits between 2000 and 2007, the option of a new Biafra was widely discussed. Many of my former colleagues at the University of Nsukka seemed to be in favour of the secession project. I talked to supporters of the main separatist organisation, Movement for the Actualisation of a Sovereign State of Biafra (MASSOB), and I discussed the project with members of Ohanaeze, a loose association of Igbo politicians, most of whom had distanced themselves from radical secessionism. In order to learn more about the resurgence of Igbo nationalism, I collected Igbo periodicals. A few of them, such as the New Republic, resembled newspapers; others, like News Round, Eastern Sunset or Weekly Hammer (with eight pages in A4 size), looked more like political pamphlets. Street vendors used back issues as wrapping paper, so they were easy to get. Most of them had been edited not in Igboland, but in Lagos, Nigeria's commercial centre and former capital which is home to a huge Igbo diaspora. Though written in English, these publications are addressed exclusively to an Igbo readership, discussing global and domestic affairs from a nationalist point of view. Articles printed here, no matter their topic, are nationalist in the sense that they assess things from the standpoint of Igbo interests. The same is true of many articles on Igbo websites and of some books and brochures written for an Igbo audience. Another source of information on Igbo nationalism are statements by Igbo governors, ministers, members of parliament and other professional politicians who are quoted in newspapers, such as Vanguard or Guardian, and in weekly magazines such as Newswatch, Tell or The News – all with a Nigeria-wide circulation and a multi-ethnic readership. Nigeria's papers and magazines are among the best in Africa. They try to be balanced in their coverage of ethnic conflicts, and they give reliable information. The same cannot be said of periodicals produced by Igbo nationalists. They provide space for Igbo all over the world to voice their opinions, and they tolerate much controversy, but they are not accurate when reporting facts.