Notes on two crabs (Crustacea, Brachyura, Dynomenidae and Iphiculidae) collected from red coral beds in northern Taiwan, including a new species of Pariphiculus Alcock, 1896.

Two brachyuran species of the families Dynonemidae and Iphiculidae are reported from red coral beds in northern Taiwan. The dynonemid Acanthodromia margarita (Alcock, 1899) has hitherto been reported from the Andaman Sea, Japan, and Philippines and the species is here recorded for the first time from Taiwan. A new species of iphiculid, Pariphiculus stellatussp. n., is also described. The new Pariphiculus, which also occurs in the Philippines, is superficially similar to P. agariciferus Ihle, 1918, a species known from Indonesia, Japan, Philippines, South China Sea, Taiwan, and Vanuatu, but can be distinguished by distinct carapace, pleonal and male first gonopod features.

Updated analysis: central venous access device infection rates in an expanded cohort of paediatric patients with severe haemophilia receiving prophylactic recombinant tissue plasminogen activator.

INTRODUCTION: Central venous access devices (CVADs) are used in the care of paediatric haemophilic patients with difficult peripheral access, but their use is limited by complications such as infection. We previously published our experience with monthly recombinant tissue plasminogen activator (r-tPA) administration to CVADs of haemophilic patients as an intervention for infection prophylaxis, which suggested a 10-fold decrease in infection rate compared to published rates without r-tPA. AIM: This study was conducted to assess the CVAD infection rate in an expanded haemophilia cohort receiving r-tPA over an extended period. METHODS: A retrospective review was performed on patients with haemophilia who received monthly r-tPA to CVADs, with data collected from January 1, 2008 to December 31, 2012. The data were merged with the previously reported data set (collected from June 1, 1998 to December 31, 2007). RESULTS: Over the entire observation period, there were 46 350 CVAD days among 32 patients [26 severe factor VIII (FVIII) deficiency, six severe FIX deficiency]. Eight patients received immune tolerance therapy for inhibitors and 24 patients received prophylactic factor administration. No patients were HIV positive. Three infections were observed, with an overall infection rate of 0.06 infections per 1000 CVAD days. CONCLUSIONS: A low CVAD infection rate, similar to that observed in our previous study (0.04 per 1000 CVAD days), was observed in this expanded haemophilia cohort treated with prophylactic r-tPA, supporting the use of monthly r-tPA as CVAD infection prophylaxis in haemophilia patients.

Acute pathophysiological responses in the normal lungs of newborn piglets exposed to pure oxygen.

AIM: We investigated the effect of short-term pure oxygen treatment on pulmonary function, serum cytokine levels, and apoptosis in the lungs of healthy newborn piglets. METHODS: Twelve newborn piglets were randomly assigned to receive pure oxygen (OXY) (N.=6) or room air (AIR: 21% oxygen) (N.=6) for 4 hours. Cardiopulmonary function serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF) α were evaluated. Histology was used to assess apoptosis and morphological differences between treatment groups. RESULTS: Four-hour treatment with 100% oxygen resulted in higher PaO2, AaDO2, and compliance of the respiratory system (Crs) in the OXY than in the AIR animals. Serum levels of IL-6 were significantly higher in OXY piglets compared with AIR piglets (P=0.009), but there were no differences between groups in the serum levels of IL-1ß and TNF-α (P=0.640 and P=0.306, respectively). The piglets in the OXY group had a greater average number of apoptotic cells in the lung than AIR piglets, although this did not reach statistical significance. CONCLUSION: Our findings indicate that treatment with 100% oxygen for 4 hours may have clinical benefit by improving pulmonary function in normal neonates with limited increases in the inflammation and apoptosis.

Force-balance percolation.

We study models of correlated percolation where there are constraints on the occupation of sites that mimic force balance, i.e., for a site to be stable requires occupied neighboring sites in all four compass directions in two dimensions. We prove rigorously that p(c) < 1 for the two-dimensional models studied. Numerical data indicate that the force-balance percolation transition is discontinuous with a growing crossover length, with perhaps the same form as the jamming percolation models, suggesting that all models belong to the same universality class with the same underlying mechanism driving the transition in both cases. We find a lower bound for the correlation length in the connected phase and that the correlation function does not appear to be a power law at the transition. Finally, we study the dynamics of the culling procedure invoked to obtain the force-balance configurations and find a dynamical exponent similar to that found in sandpile models.

Monthly recombinant tissue plasminogen activator administration to implantable central venous access devices decreases infections in children with haemophilia.

Central venous access devices (CVAD) have been effectively used in the care of haemophilia patients. This is particularly true in children, who often have difficult venous access. CVAD complications (infection and thrombosis), risk factors, and complication rates, have been well-documented. However, effective interventions which decrease complication rates have not been identified. In this study, we review our experience with the use of monthly recombinant tissue plasminogen activator (rtPA) administration in haemophilia patients with fully implanted CVADs. Data on 19 haemophilia patients with 24 CVADs were available for analysis, with a total of 24 520 CVAD days. An infection rate of 0.04 infections per 1000 CVAD days and a thrombosis rate of 0.04 thrombi per 1000 CVAD days was observed. The observed infectious complication rate is at least one logarithm lower than many published CVAD infection rates in haemophilia patients who have not received rtPA administration. No bleeding complications were noted. Monthly rtPA is safe and appears to be effective in decreasing CVAD infection rates. Larger, randomized controlled studies are indicated to validate this finding.

Amplified in breast cancer 1 expression in breast cancer.

AIMS: The amplified in breast cancer 1 (AIB1), steroid receptor co-activator family member, acts as an oestrogen receptor (ER) co-activator. Acting with HER-2, it is thought to play a role in endocrine resistance by facilitating ER-growth factor crosstalk. The aim was to analyse AIB1 expression by immunohistochemistry and study its correlations with other prognostic variables in breast cancer and its effect on survival. METHODS: A tissue microarray comprising tumours from 438 patients with 15.4 years' median follow-up was used. Interpretable AIB1 expression obtained in 395 patients was analysed along with other prognostic factors in breast cancer. RESULTS: AIB1 expression scores ranged from 0 to 30; positive AIB1 expression (score > 14) was seen in 146/395 breast cancers; it correlated negatively with ER (P = 0.003) and progesterone receptor (PR) (P = 0.007), and positively with HER-2 (P = 0.005) and tumour grade (P = 0.014). It did not correlate with nodal status (P = 0.437). Among ER+ patients, AIB1 expression showed a trend towards loss of PR expression (29% versus 20%; P = 0.14). AIB1 did not predict survival on univariate or multivariate analysis. CONCLUSIONS: AIB1 expression correlates with HER-2 expression in breast cancer and shows a trend of association with loss of PR expression in ER+ tumours. Our study supports the postulated role of AIB1 in ER-growth factor interactions.

Vacancy localization in the square dimer model.

We study the classical dimer model on a square lattice with a single vacancy by developing a graph-theoretic classification of the set of all configurations which extends the spanning tree formulation of close-packed dimers. With this formalism, we can address the question of the possible motion of the vacancy induced by dimer slidings. We find a probability 57/4-10[sqrt2] for the vacancy to be strictly jammed in an infinite system. More generally, the size distribution of the domain accessible to the vacancy is characterized by a power law decay with exponent 9/8. On a finite system, the probability that a vacancy in the bulk can reach the boundary falls off as a power law of the system size with exponent 1/4. The resultant weak localization of vacancies still allows for unbounded diffusion, characterized by a diffusion exponent that we relate to that of diffusion on spanning trees. We also implement numerical simulations of the model with both free and periodic boundary conditions.

Long-term estradiol deprivation in breast cancer cells up-regulates growth factor signaling and enhances estrogen sensitivity.

Deprivation of estrogen causes breast tumors in women to adapt and develop enhanced sensitivity to this steroid. Accordingly, women relapsing after treatment with oophorectomy, which substantially lowers estradiol for a prolonged period, respond secondarily to aromatase inhibitors with tumor regression. We have utilized in vitro and in vivo model systems to examine the biologic processes whereby long-term estradiol deprivation (LTED) causes cells to adapt and develop hypersensitivity to estradiol. Several mechanisms are associated with this response, including up-regulation of estrogen receptor-alpha (ERalpha) and the MAP kinase, phosphoinositol 3 kinase (PI3-K) and mammalian target of rapamycin (mTOR) growth factor pathways. ERalpha is four- to tenfold up-regulated and co-opts a classical growth factor pathway using Shc, Grb-2 and Sos. This induces rapid non-genomic effects which are enhanced in LTED cells. The molecules involved in the non-genomic signaling process have been identified. Estradiol binds to cell membrane-associated ERalpha, which physically associates with the adaptor protein Shc, and induces its phosphorylation. In turn, Shc binds Grb-2 and Sos, which result in the rapid activation of MAP kinase. These non-genomic effects of estradiol produce biologic effects as evidenced by Elk-1 activation and by morphologic changes in cell membranes. Additional effects include activation of the PI3-K and mTOR pathways through estradiol-induced binding of ERalpha to the IGF-I and epidermal growth factor receptors. A major question is how ERalpha locates in the plasma membrane since it does not contain an inherent membrane localization signal. We have provided evidence that the IGF-I receptor serves as an anchor for ERalpha in the plasma membrane. Estradiol causes phosphorylation of the adaptor protein, Shc and the IGF-I receptor itself. Shc, after binding to ERalpha, serves as the 'bus' which carries ERalpha to Shc-binding sites on the activated IGF-I receptors. Use of small inhibitor (si) RNA methodology to knockdown Shc allows the conclusion that Shc is needed for ERalpha to localize in the plasma membrane. In order to abrogate growth factor-induced hypersensitivity, we have utilized a drug, farnesylthiosalicylic acid, which blocks the binding of GTP-Ras to its membrane acceptor protein, galectin 1, and reduces the activation of MAP kinase. We have also shown that this drug is a potent inhibitor of mTOR as an additional mechanism of inhibition of cell proliferation. The concept of 'adaptive hypersensitivity' and the mechanisms responsible for this phenomenon have important clinical implications. The efficacy of aromatase inhibitors in patients relapsing on tamoxifen could be explained by this mechanism and inhibitors of growth factor pathways should reverse the hypersensitivity phenomenon and result in prolongation of the efficacy of hormonal therapy for breast cancer.

Adaptive hypersensitivity to estrogen: mechanisms and clinical relevance to aromatase inhibitor therapy in breast cancer treatment.

Breast tumors in women can adapt to endocrine deprivation therapy by developing hypersensitivity to estradiol. For this reason, aromatase inhibitors can be effective in women relapsing after treatment with tamoxifen or following oophorectomy. To understand the mechanisms responsible, we examined estrogenic stimulation of cell proliferation in a model system and provided in vitro and in vivo evidence that long-term estradiol deprivation (LTED) causes "adaptive hypersensitivity". The primary mechanisms responsible involve up-regulation of ER alpha as well as the MAP kinase, PI-3 kinase, and mTOR growth factor pathways. ER alpha is 4-10-fold up-regulated and co-opts a classical growth factor pathway using Shc, Grb2, and Sos. This induces rapid non-genomic effects which are enhanced in LTED cells. Estradiol binds to cell membrane associated ER alpha, physically associates with the adaptor protein Shc, and induces its phosphorylation. In turn, Shc binds Grb2 and Sos which result in the rapid activation of MAP kinase. These non-genomic effects of estradiol produce biologic effects as evidenced by Elk activation and by morphologic changes in cell membranes. Additional effects include activation of PI-3 kinase and mTOR pathways through estradiol induced binding of ER alpha to the IGF-1 and EGF receptors. Further proof of the non-genomic effects of estradiol involved use of "designer" cells which selectively express ER alpha in nucleus, cytosol, and cell membrane. We have used a new downstream inhibitor of these pathways, farnesyl-thio-salicylic acid (FTS), to block proliferation in hypersensitive cells as a model for a potentially effective strategy for treatment of patients.

HOXB13 is downregulated in colorectal cancer to confer TCF4-mediated transactivation.

Mutations in the Wnt signalling cascade are believed to cause aberrant proliferation of colorectal cells through T-cell factor-4 (TCF4) and its downstream growth-modulating factors. HOXB13 is exclusively expressed in prostate and colorectum. In prostate cancers, HOXB13 negatively regulates beta-catenin/TCF4-mediated transactivation and subsequently inhibits cell growth. To study the role of HOXB13 in colorectal tumorigenesis, we evaluated the expression of HOXB13 in 53 colorectal tumours originated from the distal left colon to rectum with their matching normal tissues using quantitative RT-PCR analysis. Expression of HOXB13 is either lost or diminished in 26 out of 42 valid tumours (62%), while expression of TCF4 RNA is not correlated with HOXB13 expression. TCF4 promoter analysis showed that HOXB13 does not regulate TCF4 at the transcriptional level. However, HOXB13 downregulated the expression of TCF4 and its target gene, c-myc, at the protein level and consequently inhibited beta-catenin/TCF-mediated signalling. Functionally, forced expression of HOXB13 drove colorectal cancer (CRC) cells into growth suppression. This is the first description of the downregulation of HOXB13 in CRC and its mechanism of action is mediated through the regulation of TCF4 protein stability. Our results suggest that loss of HOXB13 may be an important event for colorectal cell transformation, considering that over 90% of colorectal tumours retain mutations in the APC/beta-catenin pathway.

Four height variables, boundary correlations, and dissipative defects in the Abelian sandpile model.

We analyze the two-dimensional Abelian sandpile model, and demonstrate that the four height variables have different field identifications in the bulk, and along closed boundaries, but become identical, up to rescaling, along open boundaries. We consider two-point boundary correlations in detail, and discuss a number of complications that arise in the mapping from sandpile correlations to spanning tree correlations; the structure of our results suggests a conjecture that could greatly simplify future calculations. We find a number of three-point functions along closed boundaries, and propose closed boundary field identifications for the height variables. We analyze the effects of dissipative defect sites, at which the number of grains is not conserved, and show that dissipative defects along closed boundaries, and in the bulk, have no effect on any weakly allowed cluster variables, or on their correlations. Along open boundaries, we find a particularly simple field structure; we calculate all n-point correlations, for any combinations of height variables and dissipative defect sites, and find that all heights and defects are represented by the same field operator.

Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation.

Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30%) FA patients studied. Thirteen of the 80 (16.25%) were homozygotes and 11 of the 80 (13.75%) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30 percent) FA patients studied. Thirteen of the 80 (16.25 percent) were homozygotes and 11 of the 80 (13.75 percent) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

Conformal field theory correlations in the Abelian sandpile model.

We calculate all multipoint correlation functions of all local bond modifications in the two-dimensional Abelian sandpile model, both at the critical point, and in the model with dissipation. The set of local bond modifications includes, as the most physically interesting case, all weakly allowed cluster variables. The correlation functions show that all local bond modifications have scaling dimension 2, and can be written as linear combinations of operators in the central charge -2 logarithmic conformal field theory, in agreement with a form conjectured earlier by Mahieu and Ruelle in Phys. Rev. E 64, 066130 (2001). We find closed form expressions for the coefficients of the operators, and describe methods that allow their rapid calculation. We determine the fields associated with adding or removing bonds, both in the bulk, and along open and closed boundaries; some bond defects have scaling dimension 2, while others have scaling dimension 4. We also determine the corrections to bulk probabilities for local bond modifications near open and closed boundaries.

Cold perfluorochemical-induced hypothermia protects lung integrity in normal rabbits.

To test the hypothesis that intrapulmonary perfluorochemical (PFC) liquid may induce hypothermia, and to compare the effects of internal (IC), external (EC), and combined cooling techniques (EC + IC), 14 juvenile rabbits were randomized to EC by a cold blanket (4 degrees C, n = 5), IC by intrapulmonary cold PFC liquid lavage (4 degrees C, n = 5), or combined IC with PFC and EC (n = 4). Arterial blood gas, blood pressure, and lung mechanics were monitored, and lung histology was examined by light microscopy. The results showed that cooling rates and the time needed to be cooled down to 30 degrees C were significantly faster in EC and EC + IC than IC (p < 0.05). Blood gas analysis and cardiopulmonary function were within the normal range in all groups. Histological assessment revealed varied atelectasis in all lung regions in EC, whereas PFC-filled lungs (IC and EC + IC) demonstrated more homogenous expansion and no evidence of atelectasis. The results indicate that intrapulmonary PFC may be an effective technique to induce and/or augment hypothermia while supporting gas exchange, lung volume and pulmonary architecture.

Feeding behaviour: hydrothermal vent crabs feast on sea 'snow'.

The crab Xenograpsus testudinatus lives at enormously high densities around the sulphur-rich hydrothermal vents found in shallow waters off Taiwan, even though this acidic environment is low in nutrients. Here we show that these crabs swarm out of their crevices at slack water and feed on the vast numbers of zooplankton that are killed by the vents' sulphurous plumes, and that rain down like marine 'snow'. This opportunistic feeding behaviour explains how the crabs are able to survive in the adverse toxic environment of these shallow hydrothermal vents.

Boundary conditions and defect lines in the Abelian sandpile model.

We add a defect line of dissipation, or crack, to the Abelian sandpile model. We find that the defect line renormalizes to separate the two-dimensional plane into two half planes with open boundary conditions. We also show that varying the amount of dissipation at a boundary of the Abelian sandpile model does not affect the universality class of the boundary condition. We demonstrate that a universal coefficient associated with height probabilities near the defect can be used to classify boundary conditions.

Positive end-expiratory pressure modulates perfluorochemical evaporation from the lungs.

To study the effects of positive end-expiratory pressure (PEEP) level on perfluorochemical (PFC) elimination profiles (E(L)), 6 ml/kg of perflubron were instilled into healthy anesthetized rabbits. The ventilation strategy was to maintain constant minute ventilation (300 ml/kg/min) and mean airway pressure (7-8 cm H(2)O) while randomly changing the PEEP levels from 5 to 0, 1, 3, and 10 cm H(2)O, each for a period of 15 min. The PFC content in the expired gas was measured and the E(L) was calculated. There was a significant reduction in the E(L) when decreasing the PEEP levels from 5 to 0 cm H(2)O, but no differences were seen when the PEEP was increased from 5 to 10 cm H(2)O. The results indicate that PEEP levels influence PFC elimination profiles; therefore, the measurement of the E(L) and PEEP levels should be considered when optimizing supplemental PFCs during partial liquid ventilation.

Liver transplantation for acute Budd-Chiari syndrome in identical twin sisters with Factor V leiden mutation.

BACKGROUND: Budd-Chiari syndrome (BCS) is uncommon in the children. The cause of BCS comprises several diseases leading to thrombophilia. Activated protein C resistance as a result of a single gene mutation in factor V, the so called factor V Leiden (FVL), is the most common cause of thrombophilia. METHODS: We report a simultaneous occurrence of BCS in identical twin sisters of 13 years of age with heterozygous FVL mutation. RESULTS: One sister presented with acute BCS leading to fulminant hepatic failure. She underwent liver transplantation with subsequent normalization of activated protein C resistance. The other twin sister, who was diagnosed with extensive thromboses of the inferior vena cava, portal vein, and hepatic veins, was successfully managed by aggressive chemical and mechanical thrombolysis followed by therapeutic anticoagulation. Genomic DNA studies confirmed heterozygosity of FVL mutation in the sisters' father and older brother. CONCLUSIONS: The exact cause of the BCS in children should be thoroughly and rapidly investigated, and, if necessary, immediate family members should also be tested for genetic defects in factor V or concomitant thrombophilia.