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Background: Although chemotherapeutic regimens containing a taxane or platinum agent have been widely recommended for unfavourable carcinoma of unknown primary (CUP), no evidence exists for the superiority of any administered regimens. To date, the efficacy has been mostly assessed in the limited setting of phase II trials, and few attempts have been made to synthesise all available data for survival outcomes. Methods: Electronic databases were searched from 1980 to 2011. Survival results were combined for each pre-specified category of regimens using a random-effects model, and meta-regression models were used to adjust for heterogeneity in some known prognostic factors. Results: A total of 32 studies were included for meta-analysis. Tendency towards better survival outcome by platinums or taxanes was indicated. After adjustment for important prognostic factors, however, the difference between the platinum-based and non-platinum regimens became no longer significant. Survival benefits by the taxane-based regimens remained significant, with a prolonged median survival time of 1.52 months (P=0.03) and a higher 1-year survival rate of 6.25% (P=0.05), but the benefit did not sustain for 2 years. Conclusion: Although no effective therapies have been established, this meta-analysis helps to fill an important gap of evidence. However, caution should still be taken because of the potential unmeasured confounding.

Purpose: Radiological measurement scores are used by orthopaedic physiotherapists in triage and surveillance of patients with degenerative changes of the tibiofemoral and patellofemoral joints. The purpose of this study was to estimate the intra- and inter-observer reliability of a radiological measurement score to assess patellofemoral joint osteoarthritis, the Jones Patellofemoral Osteoarthritis Score (JPOS), with an orthopaedic physiotherapist and three grades of junior surgeons/doctors. Methods: A total of 390 skyline X-rays of the patellofemoral joint were reviewed on 2 occasions, 4 weeks apart, by an orthopaedic physiotherapist, 2 orthopaedic surgeons, and an orthopaedic doctor. Intra- and inter-observer reliability of the JPOS was calculated using a weighted kappa analysis. Results: The results indicated that while there was good overall intra-observer agreement for this measurement score for all assessors, inter-observer reliability was generally poor between the orthopaedic physiotherapist and the orthopaedic surgeons/doctor. Conclusion: Our findings call into question the use of the JPOS by orthopaedic physiotherapists working in triage or orthopaedic surveillance programmes with other orthopaedic clinicians.

We performed a systematic review of the optimal management of septic arthritis in children as recommended in the current English literature using MEDLINE, EMBASE, CINAHL, the Cochrane Library and reference lists of retrieved articles without date restrictions up to 31 January 2009. From 2236 citations, 227 relevant full-text articles were screened in detail; 154 papers fulfilled the inclusion criteria, from which conclusions were drawn on the management of infected joints in children.Our review showed that no single investigation, including joint aspiration, is sufficiently reliable to diagnose conclusively joint infection. The roles of aspiration, arthrotomy and arthroscopy in treatment are not clear cut, and the ideal duration of antibiotic therapy is not yet fully defined. These issues are discussed. Further large-scale, multi-centre studies are needed to delineate the optimal management of paediatric septic arthritis.

There has been debate about the role of unicompartmental knee replacement in the presence of radiologically identifiable degenerative changes of the patellofemoral joint. We studied 195 knees in 163 patients in whom an Oxford unicompartmental knee replacement had been performed for medial osteoarthritis between January 2004 and July 2007. The mean age of the patients was 66 years (51 to 93). The degree of degenerative change of the patellofemoral joint was assessed using Jones’ criteria. Functional outcome was assessed at a mean of 3.4 years (2 to 7) post-operatively, using the Oxford knee score and the Short-form 12 score. Degenerative changes of the patellofemoral joint were seen pre-operatively in 125 knees (64%) on the skyline radiographs. There was no statistically significant difference in the Oxford knee or Short-form 12 scores between those patients who had patellofemoral osteoarthritis pre-operatively and those who did not (p = 0.22 and 0.54, respectively). These results support the opinion expressed at the designer’s hospital that degenerative changes of the patellofemoral joint in isolation should not be considered to be a contraindication to medial Oxford unicompartmental knee replacement.

There is little information about the management of peri-prosthetic fracture of the humerus after total shoulder replacement (TSR). This is a retrospective review of 22 patients who underwent a revision of their original shoulder replacement for peri-prosthetic fracture of the humerus with bone loss and/or loose components. There were 20 women and two men with a mean age of 75 years (61 to 90) and a mean follow-up 42 months (12 to 91): 16 of these had undergone a previous revision TSR. Of the 22 patients, 12 were treated with a long-stemmed humeral component that bypassed the fracture. All their fractures united after a mean of 27 weeks (13 to 94). Eight patients underwent resection of the proximal humerus with endoprosthetic replacement to the level of the fracture. Two patients were managed with a clam-shell prosthesis that retained the original components. The mean Oxford shoulder score (OSS) of the original TSRs before peri-prosthetic fracture was 33 (14 to 48). The mean OSS after revision for fracture was 25 (9 to 31). Kaplan-Meier survival using re-intervention for any reason as the endpoint was 91% (95% confidence interval (CI) 68 to 98) and 60% (95% CI 30 to 80) at one and five years, respectively. There were two revisions for dislocation of the humeral head, one open reduction for modular humeral component dissociation, one internal fixation for nonunion, one trimming of a prominent screw and one re-cementation for aseptic loosening complicated by infection, ultimately requiring excision arthroplasty. Two patients sustained nerve palsies. Revision TSR after a peri-prosthetic humeral fracture associated with bone loss and/or loose components is a salvage procedure that can provide a stable platform for elbow and hand function. Good rates of union can be achieved using a stem that bypasses the fracture. There is a high rate of complications and function is not as good as with the original replacement.

Influence of Achyranthes japonica Nakai Extract (AJNE) on properties of pork sausages were studied in the present investigation. AJNE was added to sausages alone or in combination with ascorbic acid to obtain a comparative analysis on properties of control and ascorbic acid added-sausages. Results showed that addition of 0.05% AJNE led to a decrease in color L* and whiteness (W), and an increase in color b* of pork sausage samples (p

Thirty-eight fingers in 27 patients with Dupuytren’s contracture of the proximal interphalangeal joint (PIPJ) in excess of 70° were treated using a staged technique. The first stage involved applying a mini external fixator across the PIPJ for continuous extension over 6 weeks with intensive hand therapy to maintain mobility of the joint and help correct the deformity. Twice weekly during hand therapy sessions the tension of the elastic band across the mini ex-fix was increased, allowing that full active flexion of the PIPJ against the elastic band could still be achieved. The second stage, 4 weeks after the external fixator was applied, involved an open palm technique of fasciectomy for the contracted cords restricting metacarpophalangeal joint movement and dermofasciectomy with full-thickness skin grafting over the proximal phalanx for bands restricting PIPJ movement. The external fixator was used to maintain active extension force until the graft healed. It was generally removed in the outpatient clinic under ring block 2 weeks after the second stage procedure. The patients were followed for a mean of 20.6 (6–48) months. The mean preoperative PIPJ deformity improved from 75° to 37° postoperatively. Overall, 69% of results were rated as good to excellent. Only one patient reported any on-going functional problems. There were eight cases of pin site infections and one case each of loose pins, osteoarthritics at the PIPJ, reflex sympathetic dystrophy, and disease recurrence needing PIPJ fusion. We conclude that our simple staged procedure is a valid alternative in the management of severe Dupuytren’s PIPJ contracture.

Consumer perception of processed meat products is a critical issue for the meat industry. In recent years consumers are increasingly conscious about healthy diet. However, most of the processed meat products contain high amounts of fat, which are related to chronic diseases such as obesity and cardiovascular heart diseases. Health organizations have suggested to reduce the intake of total dietary fat, particularly saturated fatty acids and cholesterol, as a mean to prevent cardiovascular heart diseases (NCEP, 1988). Consumers now want low or reduced-animal fat products with high palatability and nutritional quality (Pietrasik & Duda, 2000).

In this paper we will present ASML's holistic approach to lithography for EUV. This total approach combines the various components needed to achieve the correct on-product demands of our customers in terms of patterning fidelity across the entire image field and across the entire wafer. We will start giving a general update on ASML's NXE scanner platform of which the 6 th NXE:3100 systems is now being shipped to a leading chipmaker. The emphasis will be on wafer imaging results for various applications such as flash memory and logic's SRAM. Then we will describe the second holistic component, NXE-computational lithography, which was developed to speed-up early learning on EUV and to achieve high accuracy on the wafers. Thirdly, the YieldStar angular-resolved scatterometry tool that supports the scanner's stability was used to characterize the system and calibrate the models. The wafer-results reveal in detail predicted imaging effects of NXE lithography and allow a calibration of system parameters and characterization of hardware components. We will demonstrate mask-induced imaging effects and propose an improvement of the current EUV blank or mask-making processes.

We present the results of 90 consecutive children with displaced fractures of the forearm treated by elastic stable intramedullary nailing with a mean follow-up of 6.6 months (2.0 to 17.6). Eight (9%) had open fractures and 77 (86%) had sustained a fracture of both bones. The operations were performed by orthopaedic trainees in 78 patients (86%). All fractures healed at a mean of 2.9 months (1.1 to 8.7). There was one case of delayed union of an ulnar fracture. An excellent or good functional outcome was achieved in 76 patients (84%). There was no statistical difference detected when the grade of operating surgeon, age of the patient and the diaphyseal level of the fracture were correlated with the outcome. A limited open reduction was required in 40 fractures (44%). Complications included seven cases of problematic wounds, two transient palsies of the superficial radial nerve and one case each of malunion and a post-operative compartment syndrome. At final follow-up, all children were pain-free and without limitation of sport and play activities. Our findings indicate that the functional outcome following paediatric fractures of the forearm treated by elastic stable intramedullary nailing is good, without the need for anatomical restoration of the radial bow.

1. Transcription factors such as NF-kappa B provide powerful targets for drugs to use in the treatment of cancer. In this report parthenolide (PT), a sesquiterpene lactone of herbal remedies such as feverfew (Tanacetum parthenium) with NF-kappa B inhibitory activity, markedly increased the degree of human leukaemia HL-60 cell differentiation when simultaneously combined with 5 nM 1 alpha,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)). PT by itself did not induce HL-60 cell differentiation. 2. Cytofluorometric analysis indicated that PT stimulated 1,25-(OH)(2)D(3)-induced differentiation of HL-60 cells predominantly into monocytes. 3. Pretreatment of HL-60 cells with PT before the 1,25-(OH)(2)D(3) addition also potentiated the 1,25-(OH)(2)D(3)-induced HL-60 cell differentiation in both a dose- and a time-dependent manner, in which the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-kappa B binding activity by PT. 4. In contrast, santonin, a sesquiterpene lactone without an inhibitory activity of NF-kappa B binding to the kappa B sites, did not enhance the 1,25-(OH)(2)D(3)-induced HL-60 cell differentiation. 5. In transfection experiments, PT enhanced 1,25-(OH)(2)D(3)-induced VDRE-dependent promoter activity. Furthermore, PT restored 1,25-(OH)(2)D(3)-induced VDRE-dependent promoter activity inhibited by TNF-alpha, an activator of NF-kappa B signalling pathway. 6. These results indicate that PT strongly potentiates the 1,25-(OH)(2)D(3)-induced HL-60 cell differentiation into monocytes via the inhibition of NF-kappa B activity and provide evidence that inhibition of NF-kappa B activation can be a pre-requisite to the efficient entry of promyelocytic leukaemia cells into a differentiation pathway.

The effect of silibinin, an active component of Silybum marianum, on cellular differentiation was investigated in the human promyelocytic leukemia HL-60 cell culture system. Treatment of HL-60 cells with silibinin inhibited cellular proliferation and induced cellular differentiation in a dose-dependent manner. Cytofluorometric analysis and morphologic studies indicated that silibinin induced differentiation of HL-60 cells predominantly into monocytes. Importantly, strongly synergistic induction of differentiation into monocytes was observed when silibinin was combined with 5 nM 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], a well-known differentiation inducer of HL-60 cells into the monocytic lineage. Silibinin enhanced protein kinase C (PKC) activity and increased protein levels of both PKCalpha and PKCbeta in 1,25-(OH)(2)D(3)-treated HL-60 cells. PKC and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by silibinin alone or in combination with 1,25-(OH)(2)D(3), indicating that PKC and ERK may be involved in silibinin-induced HL-60 cell differentiation.

Mouse fibroblasts (H-2(b)) were genetically engineered to express a co-stimulatory B7.1 and an IFN-gamma (Fb/IFN-gamma/B7.1). The Fb/IFN-gamma/B7.1 cells were then pulsed with an ovalbumin epitope (amino acids 257-264, SIINFEKL, H-2K(b)-restricted) as a model antigen (Fb/IFN-gamma/B7.1/OVA) and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H-2(b)). Genetically engineered fibroblasts lacking either IFN-gamma or B7.1 were constructed and used as controls. Immunization with the Fb/IFN-gamma/B7.1/OVA cells induced strong cytotoxic activity against OVA-expressing EL4 (EG7) tumor cells but not against other H-2(b) tumor cells, such as EL4, C1498, and B16F1. The magnitude of the cytotoxic response in mice with the Fb/IFN-gamma/B7.1/OVA cells was significantly higher than that in mice immunized with any other cell construct. CD8(+) T cells with OVA-specific cytotoxic activity were predominant in mice immunized with Fb/IFN-gamma/B7.1/OVA cells. Furthermore, treatment with Fb/IFN-gamma/B7.1/OVA cells significantly prolonged the survival period of EG7 tumor-bearing mice. Anti-tumor CTL immunity by the Fb/IFN-gamma/B7.1/OVA cells could be induced without the help of host antigen-presenting cells, CD4(+) T cells, or NK1.1(+) cells. Our results suggest that fibroblasts can be genetically modified into efficient antigen-presenting cells for the induction of antigen-specific CTL response in cancer immunotherapy.

Interleukin-12 (IL-12) plays a central role in the immune system by driving the immune response towards T helper 1 (Th1) type responses characterized by high IFN-gamma and low IL-4 production. In this study we investigated whether retinoid-mediated inhibition of interleukin-12 production in mouse macrophages could regulate cytokine profile of antigen (Ag)-primed CD4(+) Th cells. Pretreatment with retinoids (9-cis-RA, all-trans-RA, TTNPB) significantly inhibited IL-12 production by mouse macrophages stimulated with lipopolysaccharide (LPS) or heated-killed Listeria monocytogenes (HKL). Retinoid-pretreated macrophages reduced their ability to induce IFN-gamma and increased the ability to induce IL-4 in Ag-primed CD4(+) T cells. Addition of recombinant IL-12 to cultures of retinoid-pretreated macrophages and CD4(+) T cells restored IFN-gamma production in CD4(+) T cells. The in vivo administration of 9-cis-RA resulted in the inhibition of IL-12 production by macrophages stimulated in vitro with either LPS or HKL, leading to the inhibition of Th1 cytokine profile (decreased IFN-gamma and increased IL-4 production) in CD4(+) T cells. These findings may explain some known effects of retinoids including the inhibition of encephalitogenicity, and point to a possible therapeutic use of retinoids in the Th1-mediated immune diseases such as autoimmune diseases.

Poster: "ECR 2012 / C-1673 / Intra- and Inter-observer Reliability of Jones Patellofemoral Assessment after medial compartment UKR" by: "S. Kang1, T. O. Smith1, W. Sprenger De Rover2, S. Alazzawi3, N. Walton1; 1Norwich/UK, 2Nottingham/UK, 3London/UK"