Methods Patients in a linked study were asked to

invite a partner or other close family member to complete a self-administered postal questionnaire. Data were analysed by cancer site and time since diagnosis. Matched comparisons were made between cancer patients in the linked study and their partners. Results An expression of interest was received from 330 partners/family members, and 257 questionnaires (77.9%) were returned. Health status and levels of anxiety and depression were comparable with population norms. Respondents reported an average of 2.7 unmet needs from 34 possible options. Hospital parking, information about familial risk, help managing fear of recurrence and coordination of care were the most cited unmet needs. There was little variation in health status, psychological morbidity and unmet needs LY2606368 datasheet by cancer site or time since diagnosis. Concordance between patients and partners was low Linsitinib chemical structure for anxiety but higher with respect to positive outcomes and some unmet needs. Conclusions Most partners/family members of long-term cancer survivors report few ongoing issues. However, a small proportion (<10%) have high levels of anxiety and/or

moderate or strong unmet needs. Strategies for identifying this group and addressing their needs are required, while allowing the majority to resume normal life. Copyright (c) 2011 John Wiley & Sons, Ltd.”
“Objective To compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia. Study design Prospective, randomized cross-over study. Animals Eight healthy purpose-bred beagles aged 4years and weighing mean 13.6 +/- SD 1.9kg. Methods The dogs were instrumented

whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 mu gkg(-1) (MED), medetomidine 10 mu gkg(-1) with buy OSI-906 MK-467 250 mu gkg(-1) (MMK), or acepromazine 0.01mgkg(-1) with butorphanol 0.3mgkg(-1) (AB). Anaesthesia was induced 20minutes later with propofol and maintained with isoflurane in oxygen for 60minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO2I), systemic oxygen consumption index (VO2I) and oxygen extraction (EO2) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance.

“
“Apelin is a novel bioactive peptide as the endogenous ligand for the orphan G-protein-coupled receptor (GPCR). APJ, a receptor distributed in various tissues such as the hypothalamus Compound C and the gastrointestinal tract. Recent reports showed that apelin regulated many biological functions, including blood pressure, neuroendocrine, drinking behavior and food intake. However, the role of apelin

in regulating gastrointestinal motility remains unknown. The present study aimed to investigate the actions of intracerebroventricularly administered apelin-13 on colonic transit as well as the actions of apelin-13 on the contraction of isolated distal colon in vitro. Intracerebroventricular (i.c.v.) injection of apelin-13 (0.3, 0.5, 1 and 3 mu g/mouse) dose-dependently inhibited fecal pellet output and bead expulsion. This effect was significantly antagonized by the APJ receptor antagonist apelin-13( F13A), indicating an APJ receptor-mediated mechanism. Furthermore, naloxone could also reverse the inhibitory

effect of apelin-13 on fecal pellet GW4869 concentration output and bead expulsion, suggesting the involvement of opioid receptors in the suppressive effect of apelin-13 on distal colon transit. However, apelin-13 (10(-8)-10(-6) M) did not affect distal colonic contractions in vitro. (C) 2010 Elsevier Inc. All rights reserved.”
“Mucormycosis is a rare opportunistic fungal infection. Rhinocerebral form of the disease mainly affects diabetic or immunocompromised patients. Mucormycosis have specific tropism for blood vessels leading to mucorthrombosis and less often to mycotic aneurysms. We report

on a patient initially presenting with a severe sphenoid sinusopathy, who progressively evolved to cavernous sinus syndrome, internal carotid aneurysm followed by spontaneous thrombosis, chronic meningitis LDK378 order and ultimately fatal hypertensive hydrocephalus. Necropsy revealed a purulent infiltrate containing thin-walled, aseptate, right-angle branching, hyphae consistent with mucormycosis. His only relevant previous medical history was a transsphenoidal surgery for pituitary macroadenoma 21 years before. We hypothesize that post-surgical mucosal changes in the sphenoid sinus have been a favoring factor for delayed and invasive mucor infection.”
“Background: Cancers of the sinonasal region are rare and its survival rate remains poor because most of the patients are asymptomatic and diagnosed in advanced stages with surrounding important structures.\n\nObjectives: This study attempted to analyze the clinical and histological features in addition to survival and prognostic factors of surgical treatment of sinonasal cancers.

After seven days of adaptation, the animals were dosed with molasses-based alkane boluses (each containing 200 g C-32 and 150 g C-36) twice daily at 07:00 and 18:00 h. Concurrent with the alkane dosing, faecal spot samples were taken twice daily until the end of each run. In addition, total faecal collections were performed over the last 5 days of each run. The mean faecal recovery rate of both natural and dosed n-alkanes ranged between 0.61 and 0.86, with the recovery showing an upward trend with increasing carbon-chain length. The recovery rate of dosed alkanes was considerably higher than that of adjacent odd-chain alkanes. Whilst

diets did not differ (P >= 0.23) in the recovery of even-chain n-alkanes, an effect of diet (P <= 0.01) was observed in the PD-1/PD-L1 activation recovery of odd-chain n-alkanes. The faecal concentration of dosed alkanes reached equilibrium 3.30 days into the alkane dosing. On the assumption of similar faecal recovery of adjacent n-alkanes, intake was underestimated by 12% (P<0.001) when C-31/C-33 and C-33/C-32 alkane pairs were used and by only 1.5% (P >= 0.42) when C-35/C-36 was used. Correction for differences in the faecal recovery of adjacent n-alkanes considerably improved AZD6094 chemical structure the intake prediction

when C-31/C-32 and C-33/C-32 pairs were used. Digestibility of diets was accurately predicted using either C-36 as external marker or C-35 as internal marker corrected for incomplete recovery. NVP-BSK805 order The results showed that molasses-based boluses administered twice daily are suitable, and that knowledge of the faecal recovery rates of adjacent n-alkanes improves the reliability of the predictions. (C) 2012 Elsevier B.V. All rights reserved.”
“Novel positively charged composite nanofiltration membranes were facilely prepared by polydopamine

(PDA) deposition followed by poly(ethylene imine) (PEI) grafting on polyethersulfone (PES) substrates. Scanning election microscope (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), zeta potential measurement and water contact angle measurement were employed to characterize the surface chemical composition and morphology of the resultant membranes. The rejection of salts was increased but the pure water flux was decreased with the increase of PDA deposition time, PEI concentration, PEI reaction temperature and time. The salts rejection followed the sequence: MgCl2 bigger than CaCl2 bigger than MgSO4 bigger than Na2SO4, confirming that the membranes were positively charged. The rejection of MgCl2 could reach 73.7%, whereas the rejection of CaCl2 was 57.1%. Moreover, the membranes exhibited a superior rejection of up to 96.5% for cationic dyes. (C) 2014 Elsevier B.V. All rights reserved.

Out of seven modifications present in this tRNA, 2′-O-methylated G(m)18 was identified as necessary and sufficient

to suppress immunostimulation. Transplantation of this modification into the scaffold of yeast tRNA(Phe) also resulted in blocked immunostimulation. PKC inhibitor Moreover, an RNA preparation of an E. coli trmH mutant that lacks G(m) 18 2′-O-methyltransferase activity was significantly more stimulatory than the wild-type sample. The experiments identify the single methyl group on the 2′-oxygen of G(m)18 as a natural modification in native tRNA that, beyond its primary structural role, has acquired a secondary function as an antagonist of TLR7.”
“It is common to encounter two-dimensional dose finding in phase I trials, for example, in trials combining multiple drugs, or in single-agent trials that simultaneously search for the maximum tolerated dose (MTD) and the optimal treatment schedule. In these cases, the traditional single-agent dose-finding methods are not directly applicable. We propose a simple

and adaptive two-dimensional dose-finding design that can accommodate an type of single-agent dose-finding method. In particular, we convert the two-dimensional dose-finding trial to a series of one-dimensional dose-finding subtrials along shortened line search segments by fixing the dose level of one drug. BMS-777607 in vivo Fosbretabulin mw We then conduct the subtrials sequentially. Based on the MTD obtained from the completed one-dimensional trial. we eliminate the doses that lie Outside of the search ram-le based on the partial order, and thereby efficiently shrink the two-dimensional dose-finding space. The proposed design dramatically reduces the sample size and still maintains good performance. We illustrate the design through extensive Simulation studies motivated by clinical trials evaluating multiple drugs or close and schedule combinations. Copyright (C) 2008 John Wiley & Sons, Ltd.”
“The GH20 beta-N-acetyl-D-hexosaminidase OfHex2 from the insect Ostrinia furnacalis (Guenee) is a target potential for eco-friendly

pesticide development. Although carbohydrate-based inhibitors against beta-Nacetyl-D-hexosaminidases are widely studied, highly efficient, non-carbohydrate inhibitors are more attractive due to low cost and readily synthetic manner. Based on molecular modeling analysis of the catalytic domain of OfHex2, a series of novel naphthalimide-scaffold conjugated with a small aromatic moiety by an alkylamine spacer linker were designed and evaluated as efficiently competitive inhibitors against OfHex2. The most potent one containing naphthalimide and phenyl groups spanning by an N-alkylamine linker has a K-i value of 0.37 mu M, which is 6 fold lower than that of M-31850, the most potent non-carbohydrate inhibitor ever reported.

5 (95% confidence interval [CI] 0.9-6.9); for current smokers with -FH, OR = 3.1 95% CI 2.2-4.4); and for current smokers with +FH, OR = 6.4 ( 95% CI 3.1-13.2). The interaction constant ratio, which measured the deviation from the additive model, was significant: 2.19 (95% CI 0.80-5.99). The lower bound of the 95% CI > 0.5 signifies a departure from the additive model.\n\nConclusion: Evidence of a

gene-environment interaction with AZD1208 smoking exists for aneurysmal subarachnoid hemorrhage. This finding is important to counseling family members and for screening of intracranial aneurysm (IA) as well as the design and interpretation of genetic epidemiology of IA studies. Neurology (R) 2009; 72: 69-72″
“Background/Aims\n\nThe transjugular intrahepatic portosystemic shunt (TIPS) is technically divided into TIPS through the left branch of the portal vein (TIPS-LBPV) and TIPS through the right branch of the portal vein (TIPS-RBPV). In order to compare their advantages and disadvantages, this randomized, controlled APR-246 purchase trial was designed to investigate their outcomes in advanced cirrhotic patients.\n\nMethods\n\nSeventy-two patients were randomly placed into TIPS-LBPV (36 patients) and TIPS-RBPV (36 patients,

with four failures) groups, and they were prospectively followed for 2 years after TIPS implantation.\n\nResults\n\nPatients who underwent the two different kinds of TIPS were balanced during recruitment for this study. The incidences of overall encephalopathy and de novo encephalopathy in the TIPS-LBPV group were significantly lower than that of the TIPS-RBPV group during follow-up (P=0.036 and 0.012 respectively). The incidences

of rebleeding or re-intervention and improvement of ascites were similar between groups (P > 0.05). Patients undergoing TIPS-RBPV required more rehospitalization and incurred more costs than those who underwent TIPS-LBPV (P=0.030 and 0.039 respectively). There was no significant difference between the two groups in survival based on a survival curve constructed according to the Kaplan-Meier method (P > 0.05).\n\nConclusion\n\nPatients undergoing TIPS-LBPV had a lower incidence of encephalopathy, click here less rehospitalization and lower costs after TIPS implantation compared with patients undergoing TIPS-RBPV.”
“Gene duplication is an important mechanism for evolution of new genes. In plants, a special group of transposable elements, called Pack-MULEs or transduplicates, is able to duplicate and amplify genes or gene fragments on a large scale. Despite the abundance of Pack-MULEs, the functionality of these duplicates is not clear. Here, we present a comprehensive analysis of expression and purifying selection on 2809 Pack-MULEs in rice ( Oryza sativa), which are derived from 1501 parental genes. At least 22% of the Pack-MULEs are transcribed, and 28 Pack-MULEs have direct evidence of translation.

“
“1. Increasingly, ecologists are using functional and phylogenetic approaches to quantify the relative importance of stochastic, abiotic filtering and biotic filtering processes shaping the pattern of species co-occurrence. A remaining challenge in functional and phylogenetic analyses of tropical tree communities is to successfully integrate the functional and phylogenetic structure CCI-779 inhibitor of tree communities across spatial and size scales and habitats in a single analysis.\n\n2. We analysed the functional and phylogenetic structure of tree assemblages in a 20-ha tropical forest dynamics plot in south-west China. Because the

influence of biotic interactions may become more apparent as cohorts age, on local scales, and in resource-rich environments, we perform our analyses across three size classes, six spatial scales and six distinct habitat types, using 10 plant functional traits and a molecular phylogeny for the >400 tree taxa found in the plot.\n\n3. All traits, except leaf area and stem-specific resistance, had significant, albeit weak phylogenetic signal. For canopy species, phylogenetic clustering in small and medium size classes turned to phylogenetic overdispersion in the largest size

class and this change in dispersion with size was found in each habitat type and across all spatial scales. On fine spatial scales, functional click here dispersion changed from clustering to overdispersion with increasing size classes. However, on larger spatial scales assemblages were functionally clustered for

all size classes and habitats.\n\n4. Phylogenetic and functional structure across MK-0518 chemical structure spatial and size scales and habitats gave strong support for a deterministic model of species co-occurrence rather than for a neutral model. The results also support the hypothesis that abiotic determinism is more important at larger scales, while biotic determinism is more important on smaller scales within habitats.”
“Immunoglobulin light chain (AL) Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long-term outcomes of patients post-transplant. However, there is a paucity of literature describing outcomes of relapsed patients post-transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first-line therapy. Of those patients, 42 (10%) died within 3months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6months (95%CI 18.3, 26.3months).

In 27 EGMPC, the esophageal lesions were located at the middle (n = 16) or lower (n = 11) segment of the esophagus, while the gastric lesions were located at the gastric cardia (n = 16), fundus (n = 1), body (n = 3) and antrum (n = 7). The esophageal lesions were mainly of the hyperplastic type (n = 12) or medullary type (n = 7), while

the gastric lesions were mainly of the hyperplastic type (n = 18). A total of 119 lesions in the 59 patients with synchronous multiple carcinoma were proved by surgery or endoscopy biopsy, and preoperative upper radiographic examination detected 100 of them (84.03% sensitivity). Eighteen (52.94%) of the T(1) lesions were found during preoperative diagnosis by radiographic examination. Moreover, only 3 (3.53%) of the T(2-4) lesions were misdiagnosed.\n\nCONCLUSION: Caspase inhibitor clinical trial Hypotonic double-contrast upper gastrointestinal examination, providing accurate information about lesion morphology, location and size, can serve as a sensitive technique for the preoperative diagnosis of MPC. (C) 2011Baishideng. All rights reserved.”
“There were differences in risk factors between men and women and between two follow-up

time lengths. Osteoporosis was significantly associated with recurrent falls for women but not for men. The relationship of osteoporosis with falls in the past year decreased BX-795 during follow-up, while those of sedatives and hypnotics remained.\n\nA prospective study to investigate relationships between osteoporosis and recurrent falls at two follow-up lengths of 6 and 12 months in older men and women.\n\nIn total, 204 men and 447 women who visited an emergency department due to a fall were recruited.\n\nFor men, the risk of falling was not significantly associated with osteoporosis at 6 or 12 months. Men with a fall history were 127 and 100 %, respectively, more likely

to have a fall at 6 and 12 months than those without. JNK-IN-8 concentration Men who did not use walking aids were 97 % more likely to have a fall at 12 months than those who did. Women with osteoporosis were 246 and 104 %, respectively, more likely to have a fall at 6 and 12 months than those without. Women with a fall history were 129 and 66 %, respectively, more likely to have a fall at 6 and 12 months than those without. Women taking sedatives and hypnotics were 75 and 102 %, respectively, more likely to have a fall at 6 and 12 months than their counterparts. Women with depression were 138 % more likely to have a fall at 6 months and those using walking aids were 59 % more likely to have a fall at 12 months, compared to their counterparts.\n\nOsteoporosis is association with falls for older women but not for older men. Identifying risk factors for recurrent falls in older people may be affected by the follow-up length, as their associations are reduced over time.”
“Object. Antibiotic-impregnated shunts have yet to find widespread use in the developing world, largely due to cost.

\n\nConclusion(S): This study has demonstrated that UMLT myomectomy using either a MVI or MPI can be applied in the successful management of uncomplicated myomas. The MPI technique was more complicated, but yielded less wound pain and earlier postoperative recovery for the women during this 1-year short-term follow-up. (Fertil Steril (R) 2009;91:1945-50. (C) 2009 by American Society for Reproductive Medicine.)”
“Results of preventive health measures, diagnosis and treatment applied to Parque Indigena do Xingu native women were studied. Thirty-seven cases of uterine cervical intraepithelial lesions and invasive neoplasias were

treated in GSI-IX datasheet the local villages without referral to ail advanced medical center. LEEPs were carried out in 32 women. three cold knife conizations, one vaginal hysterectomy

and one Wertheim Meigs procedure. Results of 53.1% of LEEP surgical procedures did not have margin involvement h the lesions. Bleeding, complications were seen in 15.6%. Regular follow-up with two or three selleck products cytologic and colposcopic tests in 32 women was carried out. All cases were negative for lesions. Five women were not followed-up due mainly to logistical reasons. Health endeavors adopted in the period 2005-2007 brought about a significant reduction of precursor lesions in this native aboriginal population without screening resources.”
“Purpose of review\n\nCalcium pyrophosphate dihydrate and basic calcium phosphate crystals are the two most common calcium-containing crystals involved in rheumatic diseases. Recent literature concerning their role in the pathogenesis of osteoarthritis is reviewed.\n\nRecent findings\n\nIn some instances, these calcium

crystals might worsen osteoarthritis cartilage destruction. Laboratory investigations have identified determinants of cartilage calcification, especially a better characterization of matrix vesicle content and a better understanding of the regulation of inorganic pyrophosphate and phosphate concentration. In-vitro JQ-EZ-05 manufacturer studies have highlighted new pathogenic mechanisms of calcium crystal-induced cell activation. Several intracellular signalling pathways are activated by calcium crystals. Recent studies suggested the implication of the inflammasome complex and a pivotal role for IL-1 in pseudogout attacks and chondrocyte apoptosis in basic calcium phosphate crystal-related arthropathies.\n\nSummary\n\nAnimal models of osteoarthritis and in-vitro studies using calcium pyrophosphate dihydrate and basic calcium phosphate crystals will improve our knowledge of these common crystals and could suggest new targets for drugs, as these common diseases are ‘orphan’ with respect to therapy.”
“Study Design: Clinical case series.\n\nObjective: To show the efficacy of prophylactic inferior vena cava (IVC) filters in preventing venous thromboembolic event (VTE) in high-risk patients undergoing major spinal surgery.

Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus selleck screening library on a novel elongase, ELOVL4, involved in the synthesis of VLC-PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors.-Agbaga, M-P., M. N. A. Mandal, and R. E. Anderson. Retinal very long-chain

polyunsaturated fatty acids: new insights from studies on ELOVL4 protein. J. Lipid Res. 2010. 51: 1624- 1642.”
“The residence time of a sinking particle in the euphotic layer is usually defined as the time taken by this particle to reach for the first time the bottom of the euphotic layer. According to this definition, the concept of residence

time does not take into account the fact that many cells leaving the euphotic layer at some time can re-enter the euphotic layer at a later time. JQ1 clinical trial Therefore, the exposure time in the surface layer, i.e. the total time spent by the particles in the euphotic layer irrespective of their possible excursions outside the surface layer, is a more relevant concept to diagnose the effect of diffusion on the survival of phytoplankton cells sinking through the water column.\n\nWhile increasing the diffusion coefficient can induce both a decrease or an increase of the residence time, the exposure

time in the euphotic layer increases monotonically with the diffusion coefficient, at least when the settling velocity does not increase with depth. Turbulence is therefore shown to increase the total time spent by phytoplankton cells in the euphotic layer.\n\nThe generalization of the concept of exposure time to MK 2206 take into account the variations of the light intensity with depth or the functional response of phytoplankton cells to irradiance leads to the definition of the concepts of light exposure and effective light exposure. The former provides a measure of the total light energy received by the cells during their cycling through the water column while the latter diagnose the potential growth rate.\n\nThe exposure time, the light exposure and the effective light exposure can all be computed as the solution of a differential problem that generalizes the adjoint approach introduced by Delhez et al. (2004) for the residence time. A general analytical solution of the I D steady-state version of this equation is derived from which the properties of the different diagnostic tools can be obtained. (C) 2009 Elsevier Ltd. All rights reserved.”
“A strategy for the ortho-silylation of aryl ketone, benzaldehyde, and benzyl alcohol derivatives has been developed in which a hydroxyl group formally serves as the directing element for Ir-catalyzed arene C-H bond activation.

3, 95%CI: 1.10-1.52), while the Fc gamma RIIIA F176 polymorphism showed to be associated with lupic nephritis (OR: 1.47, 95%CI: 1.11-1.93, p = 0.006) but not with SLE susceptibility, the results in the rest of the polymorphisms studied are still contradictories.”
“Background

Craniomaxillofacial bone Ispinesib nmr defects are currently reconstructed by using computer-aided design and manufacturing (CAD/CAM) processes. We have developed a novel digital medical support system that enables us to custom-make scaffolds to repair craniomaxillofacial bone defects using three-dimensional computed tomographic (CT) images and a rapid-prototyping method.\n\nMethods We created positive molds using CT data, CAD/CAM and a rapid prototyping method using 3D printing. Custom-made poly (glycolic acid) (PGA) and polymers poly (lactic acid) (PLA) scaffolds were prefabricated by a positive-negative mold interchange technique. selleck inhibitor A laser scanning system was used to evaluate the accuracy of the PGA/PLA scaffold. Bone marrow stem cells were incubated with the scaffold to assess biocompatibility.\n\nResults The mean error was <0.3 mm and confidence was >= 95% when the error was <1 mm. Results from in vitro cell culture demonstrated that the PGA/PLA scaffold

had excellent cellular compatibility.\n\nConclusions This pilot study suggests that custom-made PGA/PLA scaffolds infiltrated with bone marrow stem cells may be effective for future treatment of craniomaxillofacial bone injuries. Copyright (C) 2009 John Wiley & Sons, Ltd.”
“Acrylic coatings based on Paraloid B72 were modified with different types of titanium dioxide nanoparticles to obtain transparent, non-yellowing and chemically stable coatings, having also self-cleaning properties. To finely disperse the inorganic nanoparticles in the polymer matrix ML323 ic50 two strategies were followed: i) ex-situ functionalization of nanoparticles and ii) use of organic inorganic coupling agents.

Characterization focussed especially on the photooxidative stability of TiO2 modified coatings. This is actually one of the most critical aspects of organic materials containing photoactive nanoparticles. The highly oxidant environment produced on the catalyst surface by photogenerated species is capable to mineralize many organic compounds, but in a poorly selective way, and this often undermines the stability of the polymer that binds the photocatalyst. Improved dispersability of TiO2 nanoparticles generally resulted in a diminished chemical stability of the acrylic medium, but by using tetraethoxysilane (TEOS) as a coupling agent, oxidation and cross-linking reactions were considerably reduced, ensuring better stability and reversibility in comparison to Paraloid coatings containing photoactive TiO2 nanoparticles without TEOS. (C) 2012 Elsevier Ltd. All rights reserved.