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Background Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil–lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population. Methods We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020. Results The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96–1.70); RMH score 2, HR 2.27 (95% CI: 1.62–3.17); RMH score 3, HR 4.14 (95% CI: 2.62–6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24–2.04), P P Conclusions We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65–0.76]), and validated the RMH model in the largest Asian study to date.

Breast cancers are heterogeneous with variable clinical courses and treatment responses.We sought to evaluate dynamic changes in the molecular landscape of HER2-negative tumors treated with chemotherapy and anti-angiogenic agents.Newly diagnosed HER2-negative breast cancer patients received low-dose sunitinib or bevacizumab prior to four 2-weekly cycles of dose-dense doxorubicin and cyclophosphamide. Tumor biopsies were obtained at baseline, after 2 weeks and after 8 weeks of chemotherapy. Next-generation sequencing was performed to assess for single nucleotide variants (SNVs) and copy number alterations (CNAs) of 440 cancer-related genes (ACTOncoThirty-four patients received sunitinib and 18 received bevacizumab. In total, 77% were hormone receptor positive (HER2-/HR+) and 23% were triple negative breast cancers (TNBC). New therapy-induced mutations were infrequent, occurring only in 13%, and appeared early after a single cycle of treatment. Seventy-two percent developed changes in the variant allele frequency (VAF) of pathogenic SNVs; the majority (51%) of these changes occurred early at 2 weeks and were sustained for 8 weeks. Changes in VAF of SNVs were most commonly seen in the PI3K/mTOR/AKT pathway; 13% developed changes in pathogenic mutations, which potentially confer sensitivity to PIK3CA inhibitors. Tumors with poor Miller-Payne response to treatment were less likely to experience changes in VAF of SNVs compared with those with good response (50% [7/14] vs 15% [4/24] had no changes observed at any timepoint, p = 0.029).Serial molecular profiling identifies early therapy-induced genomic alterations, which may guide future selection of targeted therapies in breast cancer patients who progress after standard chemotherapy.ClinicalTrials.gov: NCT02790580 (first posted June 6, 2016).

Varlitinib is a highly potent, small-molecule, pan-HER inhibitor targeting HER1, HER2, and HER4. It has demonstrated activity in gastric, biliary tract, and breast cancers.We conducted a phase Ib dose confirmation study to determine safety and early efficacy signals of varlitinib in combination with chemotherapy (paclitaxel ± carboplatin) ± subcutaneous trastuzumab.Eligible patients had advanced or metastatic solid tumors. A 3+3 dose de-escalation study design was used and pharmacokinetic analyses of varlitinib and paclitaxel were performed.Thirty-seven patients were enrolled into eight cohorts with median 4 (0-14) prior lines of palliative systemic therapies. Carboplatin area under the curve 1.5 and paclitaxel 80 mg/mThe recommended phase II dose of varlitinib with paclitaxel is 300 mg twice daily intermittently dosed. This is active in HER2+ metastatic breast cancer. Subcutaneous trastuzumab can be added safely to varlitinib and paclitaxel. This combination is currently being evaluated as neoadjuvant therapy in HER2+ breast cancer (NCT02396108).NCT02396108, date of registration: 25 March, 2015.

Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM.Forty-four patients with GCPM received IP PTX (40 mg/mThe median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%.IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

In order to optimize the operation of power generation equipment, structures, and facilities, and to maintain safety and reliability for a long period of time, non-destructive testing (NDT) has to be conducted to secure the structural integrity. Among the various NDT methods, radiographic testing (RT) is mainly used for the production/installation and scheduled maintenance of power generation facilities according to relevant codes and specifications, and they mostly have a significant effect on process delay and economic loss that occur due to duplicate application of RT and ultrasonic testing (UT). Therefore, the phased array ultrasonic testing (PAUT) is actively introduced and utilized as a new volumetric examination technique, which can reduce the use of the RT as much as possible and replace the RT in the industrial field. The PAUT is capable of high-speed inspection because not only it can control the injection of the ultrasonic beam electronically, but it can also easily test specimens with complicated shapes, which are difficult to be detected with the conventional UT. It is not easy to obtain objective and reliable testing data because the probe contact is difficult when the PAUT is used to examine the welded part with curved shapes such as a piping elbow welding part. Keywords: Please list a maximum of 6 keywords or phrases. Therefore, in this study, instead of using a wedge, which was essentially used for the inspection of the pipe with curvature structures in the conventional studies, a 5 MHz, 32 Ch Linear flexible PAUT probe that can examine a piping elbow welding part was designed and manufactured, and the usefulness was verified. In order to verify the usefulness, welding specimens were manufactured according to the ASME standard and artificial defects were processed. Finally, the possibility to overcome the limitations of the existing PAUT technologies and to improve the reliability of test results were confirmed through and signal acquisition and analysis.

Cyclin-dependent kinase 4/6 (CDK4/6) and PI3K inhibitors synergize in

Preclinical studies have demonstrated synergy between poly(ADP-ribose) polymerase (PARP) and phosphatidylinositol-3-kinase (PI3K)/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing a prospective intrapatient dose-escalation design to assess two schedules of capivasertib (AKT inhibitor) with olaparib (PARP inhibitor) in 64 patients with advanced solid tumors. Dose expansions enrolled germline BRCA1/2-mutant tumors, or BRCA1/2-wildtype cancers harboring somatic DNA damage response (DDR) or PI3K/AKT pathway alterations. The combination was well-tolerated. Recommended phase 2 doses for the two schedules were: olaparib 300mg BID with either capivasertib 400mg BID 4- days-on, 3-days-off, or capivasertib 640mg BID 2-days-on, 5-days-off. Pharmacokinetics were dose-proportional. Pharmacodynamic studies confirmed pGSK3β suppression, increased pERK and decreased BRCA1 expression. 25 (44.6%) of 56 evaluable patients achieved clinical benefit (RECIST CR/PR or stable disease ≥4 months), including patients with tumors harboring germline BRCA1/2- mutations and BRCA1/2-wildtype cancers with or without DDR and PI3K/AKT pathway alterations.

The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment.To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing.We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing.The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1-17 years). The use of BPs was significantly associated with AFFs (p 0.001, odds ratio = 25.65; 95% confidence interval = 10.74-61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment.The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.

Poly-(ADP-ribose) polymerase (PARP) inhibitors act through synthetic lethality in cells with defects in homologous recombination (HR) DNA repair caused by molecular aberrations such as BRCA mutations, and is approved for treatment in ovarian cancer, with promising clinical activity against other HR defective tumors including breast and prostate cancers. Three PARP inhibitors have been FDA approved, while another two have shown promising activity and are in late stage development. Nonetheless, both primary and secondary resistance to PARP inhibition have led to treatment failure, and the development of predictive biomarkers and the ability to identify and overcome mechanisms of resistance is vital for optimization of its clinical utility. Additionally, there has been evidence that PARP inhibition may have a therapeutic role beyond HR deficient tumors which warrants further investigation, both as single agent and in combination with other therapeutic modalities like cytotoxic chemotherapy, radiation, targeted therapy and immunotherapy. With new strategies to overcome resistance and expand its therapeutic utility, PARP inhibitors are likely to become a staple in our armamentarium of drugs in cancer therapeutics.

A 6-week feeding trial was conducted to evaluate the effect of dietary supplementation of Anionic Alkali Mineral Complex (AAMC) on growth performance, feed utilization, innate immunity, and disease resistance of L. vannamei. Graded levels of AAMC solution were included in a basal diet; 0% (Control), 0.05%, 0.1%, 0.2% and 0.4%. Shrimp fed diets supplemented with 0.2% and 0.4% AAMC had the highest growth performance, and compared to the control treatment, final body weight and specific growth rates were significantly higher (P

We investigated the effects of ultraviolet (UV) light illumination on nitrogen-doped atomic layer deposited (ALD)-ZnO:N thin film transistors (TFTs). ALD ZnO:N thin films grown at 125°C were used as active layers for back-gate TFT devices. As-fabricated ALD ZnO:N TFTs showed proper drain current modulation response to a gate voltage sweep with a 5.4 V threshold voltage and a clear pinch-off. However, the threshold voltage was significantly shifted in the negative direction by UV exposure due to an associated increase in carrier concentration, resulting in the loss of current modulation by gate voltage sweep. In addition, we observed a resistivity change in ALD ZnO:N thin films with time after UV exposure. The resistivity decreased by several orders of magnitude upon UV light exposure and recovered toward its original value after switching off the UV light. Accordingly, the transfer curves of TFT devices using a ZnO:N active layer also exhibited recovery characteristics. We formed a thin Al2O3 passivation layer on top of the TFT surface in order to suppress the recovery effect.

We investigated the ultraviolet (UV) light photostability of nitrogen doped atomic layer deposition (ALD) ZnO:N thin film transistor (TFT). ALD ZnO:N thin films were used as active layers for back-gate TFT devices. The as-fabricated ALD ZnO:N TFT grown at 125 °C shows proper drain current modulation by gate voltage sweep with 5.4 V of threshold voltage and clear pinch-off. However, the threshold voltage was significantly shifted to negative direction by UV exposure due to the increment of carrier concentration, producing the TFT device with no modulation by gate voltage. In addition, we observed the resistivity change of ALD ZnO:N thin films with time after UV exposure. The resistivity decreased by UV light exposure from 1581 to 4.532 Ω cm and then it recovered toward its original value after switching off UV light. Accordingly, the transfer curves of TFT device using ZnO:N active layer were also exhibited recovery characteristics. We adopted a thin Al2O3 passivation layer on the top surface of TFT and observed that the recovery effect was effectively suppressed.

A long-term feeding experiment was conducted to investigate the use of cottonseed and soybean meal (CS) with iron and phosphorus supplements in diets for olive flounder (Paralichthys olivaceus). Olive flounder with an initial average size of 28.5 ± 0.35 g (mean ± SD) were divided into 15 groups (three tanks per dietary treatment) and fed 480 g kg⁻¹ crude protein diets in which each of five isonitrogenous diets was formulated to contain different levels of cottonseed/soybean meal (1 : 1) to replace fish meal (FM) with iron and phosphorus supplementations. The five experimental diets were as follows: diet 1 (control), 0%CS; diet 2, 20%CS; diet 3, 30%CS; diet 4, 30%CS + FeP and diet 5, 40%CS + Fe&P. After 26 weeks of feeding trial, no significant differences were observed in weight gain, feed utilization and survival among all the treatments. The total gossypol accumulation in liver of fish fed diets supplemented with iron was significantly lower than that of fish fed diets without supplementation of iron. The results indicate that the addition of iron in diets could prevent the absorption of free gossypol. The findings in this study suggest that dietary supplements of iron and phosphorus could increase the inclusion of cottonseed and soybean meal for FM replacement in diets for marine fish species.

Palletizing tasks are necessary to promote the efficient storage and shipping of boxed products. These tasks, however, involve some of the most monotonous and physically demanding tasks in the factory. Thus, many types of robot palletizing systems have been developed, although many robot motion commands still depend on the teach pendant. That is, the operator inputs the motion command lines one by one. This is very troublesome and, most importantly, the user must know how to type the code. To solve these problems, this paper proposes a combination of an optimized pallet pattern generation algorithm, an industrial robot simulator, and a modified trajectory optimization algorithm. To integrate these modules and to define the position of the boxes, the robot and its peripherals, as well as the system layout and its coordinates, were defined. Finally, the proposed path generation algorithm, the ‘overlap method’, was tested in the designed offline programming S/W, and its computational efficiency was proven.

Recently, the application of ZnO thin films as an active channel layer of transparent thin film transistor (TFT) has become of great interest. In this study, we deposited ZnO thin films by atomic layer deposition (ALD) from diethyl Zn (DEZ) as a metal precursor and water as a reactant at growth temperatures between 100 and 250 °C. At typical growth conditions, pure ZnO thin films were obtained without any detectable carbon contamination. For comparison of key film properties including microstructure and chemical and electrical properties, ZnO films were also prepared by rf sputtering at room temperature. The microstructure analyses by X-ray diffraction have shown that both of the ALD and sputtered ZnO thin films have (002) preferred orientation. At low growth temperature Ts ≤ 125 °C, ALD ZnO films have high resistivity (> 10 Ω cm) with small mobility ( 15 cm2/V s). Meanwhile, sputtered ZnO films have much higher resistivity than ALD ZnO at most of the growth conditions studied. Based upon the experimental results, the electrical properties of ZnO thin films depending on the growth conditions for application as an active channel layer of TFT were discussed focusing on the comparisons between ALD and sputtering.

Activation of adenosine receptors in the brain reduces anxiety-like behavior in animals and humans. Because nucleoside transporters regulate adenosine levels, we used mice lacking the type 1 equilibrative nucleoside transporter (ENT1) to investigate whether ENT1 contributes to anxiety-like behavior. The ENT1 null mice spent more time in the center of an open field compared with wild-type littermates. In the elevated plus maze, ENT1 null mice entered more frequently into and spent more time exploring the open arms. The ENT1 null mice also spent more time exploring the light side of a light–dark box compared with wild-type mice. Microinjection of an ENT1-specific antagonist, nitrobenzylthioinosine (nitrobenzylmercaptopurine riboside), into the amygdala of C57BL/6J mice reduced anxiety-like behavior in the open field and elevated plus maze. These findings show that amygdala ENT1 modulates anxiety-like behavior. The ENT1 may be a drug target for the treatment of anxiety disorders.

While revision of total hip arthroplasty (THA) is being performed with increasing frequency, outcomes of repeated revisions have been rarely reported in the literature. The purpose of this study was to report mid-term outcomes of re-revision of failed revision THA acetabular components. We performed at least two revisions of the failed acetabular component in 57 patients (57 hips) between August 1996 and April 2008. Of these, 15 patients with infection were excluded and one died before 4-year evaluation. The final study cohort consisted of 41 patients (41 hips) with a mean age of 55.5 years (range, 37 to 82). Preoperative acetabular bone defects was classified as Paprosky Type IIA in 4 hips, Type IIB in 6, Type IIC in 9, Type IIIA in 16, and Type IIIB in 6. The mean duration of follow-up was 7.2 years (range, 4 to 15). Mean Harris hip score improved 45 points preoperatively to 83 points postoperatively. Six hips (14.6%) required additional revision procedure: 3 for aseptic loosening, 2 for deep infection, and 1 for recurrent instability. Complications included 2 dislocations and 1 peroneal nerve palsy. Kaplan-Meier survivorship with an end point of reoperation for any reason was 88.5% (95% CI, 78.0% to 100%) at 7.2 years. For aseptic loosening of the acetabular component, the survival was 91.8% (95% CI, 80.8% to 100%) at 7.2 years. Rerevision with contemporary uncemented cup or antiprotrusio cage for failed revision THA acetabular components showed encouraging mid-term outcomes for this technically challenging condition.

In this study, we have investigated the multi-level cell (MLC) characteristics and variability analysis of multiple resistance states of one of the most promising and extensively studied binary oxide (HfO x ) based nanometer scale RRAM stack by varying the switching current. The device size and thickness of stack layers were confirmed by transmission electron microscope (TEM) images. In the CMOS friendly stack with TiN/Ti/HfO x /TiN structure, 3 distinct levels of low resistance states (LRS) with same high resistance state (HRS) were successfully obtained which can be used in 2-bit per cell storage. It was found that the switching variability was the strong function of the number of defects in the filament or the switching current (I C ) and it significantly improved at higher I C . All the resistance levels show good inter switching ability and reliability characteristics such as read disturb immunity, read pulse endurance (>108 times) and data retention.

GaN thin films were prepared on {0001} planes of sapphire substrates by organometallic vapor phase epitaxy (OMVPE) techniques. The crystall orgaphic relation between the film and the substrate as well as the structural features of the defects in the film were investigated by transmission electron microscopy (TEM). Epitaxial relationship was observed in the GaN/sapphire heterostructure preparedin this investigation; (0001) GaN//(0001) sapphire;\(\left[ {01\bar 10} \right] GaN//\left[ {\bar 12\bar 10} \right]\) sapphire. Dislocations of Burgers vector\(\bar b = {1 \mathord{\left/ {\vphantom {1 3}} \right. \kern-\nulldelimiterspace} 3}\left[ {2\bar 1\bar 10} \right]\) were observed in the film; the propagation behavior of the dislocations exhibits a slip system\(\left\{ {10\bar 10} \right\}\left\langle {2\bar 1\bar 10} \right\rangle \) is operative in the film. Inversion domain boundary (IDB) facets lying parallel to\(\left\{ {01\bar 10} \right\}\) and\(\left\{ {\bar 12\bar 10} \right\}\) planes were observed; the type of anti-site bonds (Ga-Ga, N-N) is altemate along these IDB planes, keeping the simple stoichiometry of the compound.

Raman spectra of a series of Yb3+-doped YAG crystals were obtained with Yb3+ concentrations up to 100 at.%. Single crystals were successfully grown. No abrupt change of the spectral pattern of the Raman modes as a function of Yb3+ doping concentration was observed. From the spectral changes, it is noted that the Raman peaks shift towards lower wavenumbers in the range 450 cm−1 with increasing Yb3+ doping concentration. It is proposed that Raman modes with wavenumbers

The mathematical modelling of splicing system which involves recombination of DNA molecules was first introduced by Head in 1987. Splicing of DNA involves cutting of DNA molecules using the restriction enzymes and re-associating different fragments of DNA molecules using the ligase under some specific chemical conditions. A splicing language, L is generated if there exists a splicing system S for which L = L(S). There are different types of splicing systems which have been discussed by various researchers. Among them are the persistent splicing system, null-context and uniform splicing system. In this paper, some molecular examples on null-context splicing system and uniform splicing systems with different initial strings and combination of restriction enzymes will be discussed. Applications of automata theory on some molecular examples of null-context and uniform splicing languages will also be presented in this paper.

This paper evaluates existing dynamic hardening models and fracture strains for metallic materials of typical crystalline structures: 4130 steel (BCC); OFHC copper (FCC); and Ti6Al4V (HCP). Uniaxial tensile and fracture tests of the representative materials are carried out at intermediate strain rate. In order to describe the dynamic hardening characteristics, several models are compared for each material and the most applicable model for a specific material has been recommended. The fracture tests at strain rates ranging from 0.001s to 100s are conducted with several types of the pure shear, dog bone and grooved specimens for the strain paths of the pure shear, uniaxial tension and plain strain conditions. The fracture strain and the strain path are measured on the surface of the specimen and the Lou-Huh ductile fracture criterion is implemented to describe the fracture loci with respect to the strain rate.

We investigated the ultraviolet (UV) light photostability of plasma‐enhanced and thermal atomic layer deposition of ZnO thin film transistor (TFT). The negative shift of threshold voltage was similarly observed in both cases by UV exposure due to the increment of carrier concentration. Additionally, the transfer curves of TFT using thermal ALD ZnO:N active layer were exhibited recovery characteristics.

A ductile fracture criterion is newly proposed to accurately predict forming limit diagrams (FLD) of sheet metals. The new ductile fracture criterion is based on the effect of the non-dimensional stress triaxiality, the stress concentration factor and the effective plastic strain on the nucleation, growth and coalescence of voids. The new ductile fracture criterion has been applied to estimate the formability of four kind advanced high strength steels (AHSS): DP780, DP980, TRIP590, and TWIP980. FLDs predicted are compared with experimental results and those predicted by other ductile fracture criteria. The comparison demonstrates that FLDs predicted by the new ductile fracture criterion are in better agreement with experimental FLDs than those predicted by other ductile fracture criteria. The better agreement of FLDs predicted by the new ductile fracture criterion is because conventional ductile fracture criteria were proposed for fracture prediction in bulk metal forming while the new one is proposed to predict the onset of fracture in sheet metal forming processes.

An explicit integrator for wave propagation analysis of heterogeneous solids is presented, which is aimed at minimizing spurious oscillations when the wave fronts pass through several zones of different wave speeds. Hence, the present method can be applied to multi-physics and multi-scale problems in which discontinuous spatial and temporal discontinuities need to be accurately captured without incurring spurious oscillations. The essence of the present method is a combination of two wave capturing characteristics: post-shock oscillations of most existing explicit integrators and a new integration construction that is designed to triggers shock-front oscillations. It is shown that a judicious combination of these two characteristics substantially reduces both shock-front and post-shock oscillations. The performance of the new method is demonstrated as applied to one-dimensional wave propagation through a uniform bar with varying courant numbers, then to heterogeneous bars.Copyright © 2011 by ASME

[1] Structural complexity is common at the terminations of earthquake surface ruptures; similar deformation may therefore be expected at the end zones of earthquake ruptures at depth. The 8.2 km long Glacier Lakes fault (GLF) in the Sierra Nevada is a left-lateral strike-slip fault with a maximum observed displacement of 125 m. Within the fault, pseudotachylytes crosscut cataclasites, showing that displacement on the GLF was accommodated at least partly by seismic slip. The western termination of the GLF is defined by a gradual decrease in the displacement on the main fault, accompanied by a 1.4 km wide zone of secondary faulting in the dilational quadrant of the GLF. The secondary faults splay counterclockwise from the main fault trace forming average angles of 39° with the main fault. Slip vectors defined by slickenlines plunge more steeply west for these splay faults than for the GLF. Static stress transfer modeling shows that the orientations of the splays, and the plunge of displacement on those splays, are consistent with displacement on the main fault. The GLF termination structure shows that structural complexity is present at the terminations of faults at seismogenic depths and therefore ruptures that propagate beyond fault terminations, or through step overs between two faults, will likely interact with complex secondary fault structures. Models of dynamic rupture propagation must account for the effect of preexisting structures on the elastic properties of the host rock. Additionally, aftershock distributions and focal mechanisms may be controlled by the geometry and kinematics of structures present at fault terminations.

Total hip arthroplasty with use of metal-on-metal bearings has been reintroduced as an alternative to metal-on-polyethylene bearings because of theoretical advantages such as reduced wear and a lower prevalence of osteolysis. However, we have observed early osteolysis in nine patients (ten hips) out of 165 patients (169 hips) who had been managed with total hip replacements using a contemporary metal-on-metal hip design and investigated the possible etiologic role of metal hypersensitivity. The nine patients who had an osteolytic lesion had a significantly higher prevalence of hypersensitivity to cobalt, as determined by patch testing, when compared to nine controls (p = 0.031). The retrieved periprosthetic tissues from the two revised hips showed no evidence of metallic staining, but microscopic analysis revealed a perivascular accumulation of CD3-positive T-cells and CD68-positive macrophages, and an absence of both particle-laden macrophages and polymorphonuclear cells. Immunohistochemical analysis demonstrated that potent bone-resorbing cytokines such as IL-1β and TNF-α were produced mainly by infiltrated lymphocytes and activated macrophages. These findings raise the possibility that early osteolysis in this second-generation metal-on-metal hip replacement is associated with abnormalities consistent with delayed-type hypersensitivity to metal.

Loss of coxsackievirus and adenovirus receptor (CAR) is frequently observed in malignant cancer, hampering adenoviral gene therapy approaches. Complexing adenovirus with cationic liposomes can increase adenoviral transgene expression, particularly in cells with CAR-deficiency. We investigated whether other factors such as lipid composition might be involved in determining the efficiency of liposome-complexed adenoviral gene transfer in cancer cells.Human cancer cell lines with different expression levels of CAR were infected with a GFP transgene. The efficiency of transgene expression was assessed by determining GFP expression using FACS analysis.The efficiency of liposome-complexed adenoviral gene transfer was dependent on the lipid composition constituting liposomes. Polyethylene glycol (PEG)-containing liposomes were most effective in increasing liposome-complexed adenoviral gene transfer. In CAR-deficient cells, use of PEG-containing liposomes enhanced adenoviral gene transfer, whereas in CAR-expressing cells enhancement varied depending on cell type. In some CAR-expressing cells, the effect of liposome complexing was even comparable to that in CAR-deficient cells. Increased adenoviral transgene expression following complexing with PEG-containing liposomes correlated with liposome uptake in cancer cells.Liposome-complexed adenoviral gene transfer appears to depend on lipid composition and the level of liposome uptake by cancer cells, in addition to CAR levels. Our study suggest that these multiple factors should be considered in designing liposome-complexed adenoviral vectors to improve outcomes of current adenoviral cancer gene therapies.

Information on the Web, which are conglomeration of heterogeneous data, such as texts, images and audio clips, are often accessed through documents written according to the HTML specification. According to the HTML specification, HTML documents are semistructured in nature. We propose a high-level stack machine (HSM) which accesses an HTML document through its URL and constructs a semistructured data graph (SDG) of the document. The SDG of an HTML document H precisely captures the structure of the semistructured data embedded in H based on the dependency relationship among the data objects in H. HSM is configurable to accommodate a user's interest with respect to the HTML elements in H to be considered during the construction process of the SDG of H.

Introduction: ALDH2 is an enzyme involved in major oxidative pathway of alcohol metabolism while GSTM1 is a drug-metabolizing enzyme of acetaldehyde. It has been reported that the mutant ALDH2 allele and the absence of GSTM1 contributes to increased oral cancer risk due to reduced acetaldehyde metabolism. This study aims to determine ALDH2 and GSTM1 polymorphisms and its association with oral cancer risk. Method: An unmatched case-control study was conducted using 163 oral cancer patients and 87 non-cancer subjects selected from the OCRCC database. ALDH2 and GSTM1 genotypes were determined using PCR-RFLP from peripheral blood. Multiple logistic regression was employed to assess association between polymorphisms and oral cancer risk. Results: Most common risk habit was betel-quid chewing (44.0%), followed by smoking (30.4%) and alcohol drinking (29.6%). The prevalence of ALDH2 polymorphism is only 5.7%, while GSTM1 null is seen in 51.2%. Alcohol drinking and the combination of ALDH2 polymorphism and alcohol consumption is significantly associated with increased risk of oral cancer (p < 0.001). Discussion: In this population, although the prevalence of alcohol consumption is low compared to other populations, alcohol drinking has been found to significantly increase oral cancer risk, even after adjusting for confounding factors (age, gender and ethnic) (aOR 6.8, 95% CI 2.6, 18.1). The prevalence of ALDH2 polymorphism was found to be much lower compared to other Asian population such as the Japanese and Taiwanese. In relation to oral cancer risk, no significant association was seen for both the polymorphisms of ALDH2 and GSTM1. However, when analysis was done for the combination of ALDH2 polymorphism and alcohol consumption, those who concurrently exhibit ALDH2 polymorphism and consumed alcohol was found to be 6 times more likely to develop oral cancer (aOR 6.6, 95% CI 2.4, 17.9). No such association was observed for the combination of GSTM1 polymorphism and alcohol consumption. In conclusion, alcohol consumption is a significant independent risk factor for oral cancer among Malaysians while ALDH2 polymorphism together with the habit of alcohol drinking also confers an increased risk for oral cancer.

To determine the prophylactic effect of 0.2% brimonidine in reducing the elevated intraocular pressure (IOP) in patients undergoing Nd:YAG laser posterior capsulotomy.The 81 patients (81 eyes), who underwent Nd:YAG laser posterior capsulotomy, were allocated to two treatment groups. One drop of 0.2% brimonidine or vehicle was instilled 1 hour preoperatively and one drop immediately after capsulotomy. IOPs were measured preoperatively and 1, 2, 3, and 24 hours postoperatively.Intraocular pressure decreased from the baseline in the brimonidine group by the third postoperative hour (P0.05), while the vehicle group exhibited an increase. Intraocular pressure elevations of 5 mm Hg or greater occurred in 7.3% (3/41) in the brimonidine group compared to 20.0% (8/40) in the vehicle group. IOP elevations of 10 mm Hg or greater occurred in 2.4% (1/41) in the brimonidine group compared to 7.5% (3/40) in the vehicle group.One drop of 0.2% brimonidine instilled 1 hour preoperatively and immediately after capsulotomy was found to be efficacious and safe in preventing IOP elevations that frequently follow Nd:YAG laser posterior capsulotomy.

Autosomal dominantly transmitted hereditary multiple exostoses is an uncommon disorder consisting of multiple projections of bone capped by cartilage. The lesions are most numerous in the metaphyses of long bones but may appear on flat bones. Sarcomatous transformation occurs in 1-25% of patients. We report a 33-year-old man with sciatica, previously diagnosed as hereditary multiple exostoses, presenting with multiple peripheral nerve compressions. Electrodiagnostic studies showed profound axon-loss multiple neuropathies involving the sciatic, superior gluteal, and inferior gluteal nerves. Magnetic resonance imaging of the left pelvis showed a large mass in the sacral area that was suggestive of a chondrosarcoma. An open intralesional excision biopsy confirmed chondrosarcoma transformed from chondromatosis. Excision of the lesion was effective in eliminating the impingement of nerves and retarding progressive osseous growth. We suggest that malignant transformation be suspected in cases with focal compression neuropathy of patients known to have multiple exostoses. Osteochondroma as a possible cause for compression neuropathy is discussed.

Liquid and volatile (hfac)CuL compounds where hfac = 1,1,1,5,5,5-hexafluoro- 2,4-pentanedionate and L = 1-pentene (1), acetyltrimethylsilane (2), and vinyltri- methoxysilane (3) were newly developed for reproducible copper deposition. During CVD processes, no premature decomposition of the precursor was observed in the source reservoir that contained the mixture of (hfac)CuL and excess free ligand L. Pure Cu films were deposited in the deposition temperature range 180°C ˜ 220°C