Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy.     

Visual Notes and the Acquisition of Architectural Knowledge

This article discusses the value and purpose of drawing in its relationship to the design process and understanding architecture. The authors base much of their discussion on their own experiences in teaching both drawing and architectural design to undergraduates. These experiences however are informed and supported both by architectural history and theory and theories of perception and art. The authors discuss the importance of visual notes to architects of the past, note both the decline of the usage of visual notes in the twentieth century as well as their continued use by important architects of our time. This article stresses the analytical and critical value of such drawing as opposed to its pictorial purposes.     

Influence of a wide range of calcium intakes on tissue distribution of macroelements and microelements in dairy calves

Sixteen intact male Holstein calves averaging 86 kg and 63 d of age were assigned randomly to four treatment groups. The four treatment diets contained .17, .67, 1.31, and 2.35% Ca on an as-fed basis. The resulting Ca:P ratios with P held constant at about .34% were .47:1, 1.92:1, 3.83:1, and 7.20:1. Calves were fed diets at 3% of their body weights for 4 wk. Magnesium in the bone ash and serum was lowered by the 2.35% Ca treatment. Serum inorganic P was also reduced by the highest Ca diet during the last 2 wk of the experiment. Liver had the highest concentration of Zn in calves fed .67% Ca, and the muscle from calves fed 1.31% Ca diet had the lowest amount of Zn. Copper was reduced in pancreas for 1.31% Ca diet, but Ca was highest in the muscle and heart at the .67% Ca treatment. Weight gains and feed efficiencies were not affected by Ca. Fecal pH was different among treatments and increased as Ca intake increased. Young growing dairy calves can adapt to a wide range of Ca intakes and Ca:P ratios and maintain a moderate growth rate for 4 wk. It appears that excessive dietary Ca may affect concentrations of Zn, Fe, Cu, and Mn in some body tissues, but the magnitude of the effect is relatively small.     

Anaerobic methane oxidation and aerobic methane production in an east African great lake (Lake Kivu)

We investigated CH₄ oxidation in the water column of Lake Kivu, a deep meromictic tropical lake with CH₄-rich anoxic deep waters. Depth profiles of dissolved gases (CH₄ and N₂O) and a diversity of potential electron acceptors for anaerobic CH₄ oxidation (NO₃^?, SO₄^2?, Fe and Mn oxides) were determined during six field campaigns between June 2011 and August 2014. Denitrification measurements based on stable isotope labelling experiments were performed twice. In addition, we quantified aerobic and anaerobic CH₄ oxidation, NO₃^? and SO₄^2? consumption rates, with and without the presence of an inhibitor of SO₄^2?-reducing bacteria activity. Aerobic CH₄ production was also measured in parallel incubations with the addition of an inhibitor of aerobic CH₄ oxidation. The maximum aerobic and anaerobic CH₄ oxidation rates were estimated to be 27?±?2 and 16?±?8?μmol/L/d, respectively. We observed a difference in the relative importance of aerobic and anaerobic CH₄ oxidation during the rainy and the dry season, with a greater role for aerobic oxidation during the dry season. Lower anaerobic CH₄ oxidation rates were measured in presence of molybdate in half of the measurements, suggesting the occurrence of linkage between SO₄^2? reduction and anaerobic CH₄ oxidation. NO₃^? consumption and dissolved Mn production rates were never high enough to sustain the measured anaerobic CH₄ oxidation, reinforcing the idea of a coupling between SO₄^2? reduction and CH₄ oxidation in the anoxic waters of Lake Kivu. Finally, significant rates (up to 0.37?μmol/L/d) of pelagic CH₄ production were also measured in oxygenated waters.     

LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta-sarcoglycan exon 3

Four of the currently recognized autosomal recessive limb-girdle muscular dystrophies (LGMD type 2C-F) are caused by mutations in the genes encoding components of the sarcoglycan complex. LGMD 2C, caused by mutations in gamma-sarcoglycan, is prevalent in northern Africa, especially in Tunisia, where this type of muscular dystrophy was originally described. Although the disease initially was assumed to be genetically homogeneous in this region, linkage to the alpha-sarcoglycan locus (LGMD 2D) has also been found. We have now identified the first Tunisian family with beta-sarcoglycanopathy (LGMD 2E), further adding to the genetic heterogeneity of autosomal recessive LGMD in this population. Direct sequencing of the beta-sarcoglycan gene revealed a homozygous mutation (G272-->T, Arg91Leu) in exon 3. This change affects the same arginine residue in the immediate extracellular domain of the protein that was mutated to a proline (G272-->C, Arg91Pro) in a Brazilian family with a severe form of the disease. Immunohistochemical analysis for the sarcoglycan complex demonstrates absence of the known components of the complex in both of these families. We postulate that the immediate extracellular domain of beta-sarcoglycan may be important for the assembly and/or maintenance of this complex, potentially mediated by disulfide-bond formation to another sarcoglycan via the single cysteine residue in that domain.     

Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: role of the p38 and p42/44 mitogen-activated protein kinases

IL-10 is an anti-inflammatory cytokine with potent immunomodulatory effects, including inhibition of cytokine production. However, regulation of monocyte IL-10 production is poorly understood. In this report we have investigated the mechanisms of LPS-induced IL-10 production by human peripheral blood monocytes and demonstrate that IL-10 synthesis is uniquely dependent on the endogenous proinflammatory cytokines IL-1 and/or TNF-alpha. LPS signal transduction in monocytes has been shown to involve activation of the p38 and p42 mitogen-activated protein kinase (MAPK) cascades. The results in this paper indicate that inhibition of p38 MAPK potently inhibited the production of IL-10, IL-1beta, and TNF-alpha, whereas blockade of the p42/44 MAPK pathway, while partially inhibiting TNF-alpha and IL-1beta production, had no effect on monocyte secretion of IL-10. Furthermore, neither the inhibition of monocyte TNF-alpha induced by IL-10 nor the stimulation of soluble TNF receptor production was affected by inhibition of the p42/44 MAPK pathway, suggesting that this signaling event is not involved in either monocyte production of or anti-inflammatory responses to IL-10. These data raise the interesting possibility that proinflammatory TNF-alpha-mediated effects may be selectively blocked without modulating the induction or the response to IL-10, whereas the signaling events associated with the anti-inflammatory events induced by IL-10 remain to be elucidated.     

Surface-based Transport Model for Mixed-Size Sediment

We present a transport model for mixed sand/gravel sediments. Fractional transport rates are referenced to the size distribution of the bed surface, rather than subsurface, making the model completely explicit and capable of predicting transient conditions. The model is developed using a new data set of 48 coupled observations of flow, transport, and bed surface grain size using five different sediments. The model incorporates a hiding function that resolves discrepancies observed among earlier hiding functions. The model uses the full size distribution of the bed surface, including sand, and incorporates a nonlinear effect of sand content on gravel transport rate not included in previous models. The model shares some common elements with two previous surface-based transport models, but differs in using the full surface size distribution and in that it is directly developed from a relatively comprehensive data set with unambiguous measurement of surface grain size over a range of flow, transport rate, and sediments.     

The low-affinity dihydropyridine receptor and Na+/Ca2+ exchanger are associated in adrenal medullary mitochondria

The effect of Ca2+ channel-acting drugs on bovine adrenal mitochondria Ca2+ movements was investigated. Mitochondrial Ca2+ uptake is performed by an energy-driven Ca2+ uniporter with a Km of 20.9 +/- 3.2 microM and Vmax of 148.1 +/- 7.2 nmol 45Ca2+ min-1 mg-1. Ca2+ release is performed through an Na+/Ca2+ antiporter with a Km for Na+ of 4.2 +/- 0.5 mM, a Vmax of 7.5 +/- 0.4 nmol 45Ca2+ min-1 mg-1, and a Hill coefficient of 1.4 +/- 0.2 Ca2+ efflux through the mitochondrial Na+/Ca2+ exchanger was inhibited by several dihydropyridines (nitrendipine, felodipine, nimodipine, (+)isradipine) and by the benzothiazepine diltiazem with similar potencies. In contrast, neither CGP 28392, Bay-K-8644, amlodipine, nor verapamil had any effect on Ca2+ efflux. Nitrendipine at 20 microM modified neither the Km nor the Hill coefficient for Na+, whereas the Vmax was reduced to 2.9 nmol 45Ca2+ min-1 mg-1, thus demonstrating noncompetitive modulation of the Na+/Ca2+ exchanger. None of the Ca2+ channel-acting drugs assayed at 100 microM affected Ca2+ influx through the uniporter. Ca2+ channel blockers inhibited the Na+/Ca2+ antiporter and displaced the specific binding of [3H]nitrendipine to intact mitochondria with Ki values similar to the IC50s obtained for the inhibition of the Ca2+ efflux. Ca2+ channel-acting drugs that did not inhibit the Na+/Ca2+ exchanger (amlodipine, CGP 28392, Bay-K-9644, and verapamil, at concentrations of 100 microM or higher) had no effect on [3H]nitrendipine binding. These results suggest that the adrenomedullary mitochondrial dihydropyridine receptor is associated with the Na+/Ca2+ exchanger.     

Canine bronchial sustained contraction in Ca2+-free medium: role of intracellular Ca2+

We evaluated whether cartilage was a source of Ca2+ and the possible role of Ca2+ recycling in the sustained bronchial contraction (SBC) induced by carbachol (Cch) in Ca2+-free medium. Canine first-order bronchi were studied with cartilage and epithelium (+CAR + EPI) and without these structures individually (-CAR + EPI and +CAR - EPI) or together (-CAR - EPI). After cartilage removal (-CAR - EPI or -CAR + EPI) Cch produced a transient contraction in Ca2+-free medium. Removal of the epithelium alone had minor effects on the magnitude of the SBC but increased the effect of removal of cartilage to diminish the SBC. Bronchial strips with cartilage were able to respond to Cch with lower Ca2+ concentrations (10-100 microM) than could dissected preparations. Preincubation with BAY K 8644 (30-1000 nM) or 60 mM KCl or -CAR - EPI tissues converted the transient contractions to Cch in Ca2+-free medium to sustained contractions. In microelectrode studies, 50 nM Cch induced membrane oscillations in solutions with 2.5 mM Ca2+ in bronchial preparations, plus or minus cartilage, and in undissected tissues in Ca2+-free medium but not in -CAR - EPI tissues. Preincubation with 1 microM BAY K 8644 in Ca(2+)-free medium restored these oscillations in -CAR - EPI tissues. The release of 45Ca2+ from cartilage was too rapid to provide a reservoir of Ca2+ to support multiple SBCs in Ca2+-free medium. Moreover, in the Ca2+-free medium (with 10 nM Ca2+ after tissue +CAR + EPI incubation) excitatory junction potentials rapidly disappeared. Addition of 1 microM nifedipine or 1 mM EGTA during the SBC of +CAR + EPI tissues produced complete relaxation. A transient contraction to Cch occurred with prior addition of nifedipine. Inhibition of the sarcoplasmic reticulum Ca2+ pump by tissue incubation with cyclopiazonic acid (CPA; 10 microM), or briefly with 1 mM EGTA significantly diminished the SBC induced by Cch in Ca2+-free medium. CPA and EGTA together abolished the Cch-induced SBC. Thus, cartilage plays a more complex role than as a Ca2+ reservoir to support the SBC induced by Cch in Ca2+-free solution; its removal affects the process supporting SBCs involving intracellular Ca2+ storage and Ca2+ entrance through voltage-dependent channels.     

Thoracoscopic-assisted pulmonary resection in lung cancer

BACKGROUND: Thoracoscopic-assisted pulmonary resection for lung cancer is controversial. The appropriateness of this approach has to be compared with the golden standard of an open resection. METHODS: This study consists of 66 patients with a clinical stage 1 disease. A thoracoscopic exploration was executed in 41 patients. Only in 16 cases was a thoracoscopic resection finally possible. The clinical and pathological TNM classification, the histological types and the surgical procedure are reported. The reasons for conversion are documented. RESULTS: To investigate the appropriateness of the thoracoscopic approach we evaluated only the pathologically proven stage 1 disease in both groups. Postoperative complications, hospital stay and survival are compared. CONCLUSION: Until now we can conclude that there is no adverse effect on survival because of the thoracoscopic approach.