The Critical Success Factors For Public-Private Partnership Highway Construction Project in Malaysia

The Public-Private Partnership (PPP) approach has been widely used in the development of major infrastructure and building projects all over the world and is considered as one of the effective ways to achieve value-for-money procurement for the public sector. PPP usually requires public authorities and private contractors to collaborate through long-term concession contract where the latter has the obligation to provide the public services desired for the public sector. PPP has recently being introduced in Malaysia as a revised approach towards improving its existing privatization approach in the procurement of public sector projects. Thus, it is essential to determine the critical success factor (CSF) for public sector projects in Malaysia. The Butterworth Outer Ring Road (BORR), which is one of the PPP-oriented infrastructure projects currently operating in Malaysia, has been used as a case study in order to achieve this aim. An extensive interview and structured questionnaires have been used as data acquisition means to elicit the perception of public sector clients in regards to the CSF for the BORR project. As a result, effective communication system, good project governance, responsibility and commitment of public and private sectors, competitive procurement process and ability to delegate authority have been identified as the top five CSF for the BORR expressway in Malaysia

Criteria influencing pedestrian-friendliness of first/last mile transit journey using Analytical Network Process (ANP) group judgement

The pedestrian-friendliness of the first/last mile (FLM) transit journey is one of the keys in influencing the quality of transit services. The demands of transit riders are increasing as they have started to ask for more than just accessibility which includes a good walking environment to access the service. Most local governments are aware of this as many of them have the guidelines in planning for a walkable transit services. However, they need to prioritise the criteria influencing pedestrian-friendliness accordingly. This paper proposes a framework for evaluating the priorities of criteria influencing pedestrian-friendliness by using Analytical Network Process (ANP) which relies on group judgement from experts who have wide knowledge and experience within the scope of the study. It can be conducted in six stages which are (1) determining criteria influencing pedestrian-friendliness (2) developing ANP model of the criteria and their dependencies, (3) obtaining experts judgement, (4) aggregating the criteria’s priorities, (5) deriving group judgement of the criteria’s priorities, and (6) ranking the criteria accordingly. In the end, this study will suggest the priorities for criteria influencing pedestrian-friendliness which can be used as reference in planning for walking environment to access transit services. This study highlighted nineteen criteria that could be used in representing the pedestrian-friendliness of FLM. Based on the analysis, it is suggested that from the nineteen criteria, the presence of signage showing direction is the most important criterion followed by roofed walkway, convenience in term of walking time, access to public parks and presence of traffic lights

A Web Resource for Designing Subunit Vaccine Against Major Pathogenic Species of Bacteria

Evolution has led to the expansion of survival strategies in pathogens including bacteria and emergence of drug resistant strains proved to be a major global threat. Vaccination is a promising strategy to protect human population. Reverse vaccinology is a more robust vaccine development approach especially with the availability of large-scale sequencing data and rapidly dropping cost of the techniques for acquiring such data from various organisms. The present study implements an immunoinformatic approach for screening the possible antigenic proteins among various pathogenic bacteria to systemically arrive at epitope-based vaccine candidates against 14 pathogenic bacteria. Thousand four hundred and fifty nine virulence factors and Five hundred and forty six products of essential genes were appraised as target proteins to predict potential epitopes with potential to stimulate different arms of the immune system. To address the self-tolerance, self-epitopes were identified by mapping on 1000 human proteome and were removed. Our analysis revealed that 21proteins from 5 bacterial species were found as virulent as well as essential to their survival, proved to be most suitable vaccine target against these species. In addition to the prediction of MHC-II binders, B cell and T cell epitopes as well as adjuvants individually from proteins of all 14 bacterial species, a stringent criteria lead us to identify 252 unique epitopes, which are predicted to be T-cell epitopes, B-cell epitopes, MHC II binders and Vaccine Adjuvants. In order to provide service to scientific community, we developed a web server VacTarBac for designing of vaccines against above species of bacteria. This platform integrates a number of tools that includes visualization tools to present antigenicity/epitopes density on an antigenic sequence. These tools will help users to identify most promiscuous vaccine candidates in a pathogenic antigen. This server VacTarBac is available from URL (http://webs.iiitd.edu.in/raghava/vactarbac/)

A phase-III study of recombinant interleukin 2 and 5-fluorouracil chemotherapy in patients with metastatic colorectal cancer.

Sixteen patients with metastatic colorectal cancer have been treated with a regimen involving an 120 h continuous infusion of rIL-2, 18 x 10(6) iu m-2 day followed by three injections of 5FU 600 mg m-2 at weekly intervals. Entry criteria included no previous chemotherapy, ambulatory performance status, and a measurable lesion. In most cases side effects were easily manageable and only one patient required transfer to an intensive care unit with the capillary leak syndrome. In three patients persistent hypotension was found to be unrelated to treatment with rIL-2, being caused respectively by a line infection, pulmonary embolus, and bowel perforation. This last proved a fatal complication. Five patients (33%; [95% confidence limits, 11.8%-61.6%]) achieved a partial response, and two non-responders later achieved a partial response when treated with weekly 5FU. This regimen is currently being evaluated in a phase-III randomised controlled trial

Production of bioethanol through enzymatic hydrolysis of potato

Due to gradual decrease in petroleum resources and impacts of these wastes on the environment, there is a need to utilize the wastes of potatoes to get wealth out of wastes and clean the environment. In this study, potato wastes were investigated as source of bioethanol. 100 g potato powder was mixed with 1 L distilled water in two separate beakers to form potato slurry. Bioethanol production was investigated using effect of pH, temperature and mixture of digesting enzymes after scarification and fermentation. The results show that significant (p<0.05) bioethanol was produced at 35°C and at pH 5.5. This investigation also reveals that mixture of enzymes significantly enhanced (p<0.05) bioethanol production compared to non treated mixture. Maximum bioethanol productions were due to the presence of sugar in potatoes.Key words: Bioethanol, potato, ph, temperature, liquefaction

Results of a multicentre UK-wide compassionate use programme evaluating the efficacy of idelalisib monotherapy in relapsed, refractory follicular lymphoma.

Follicular lymphoma (FL) is an indolent B-cell malignancy with a variable course. Standard immuno-chemotherapy incorporate alkylator and anti-CD20 monoclonal antibody as first line (Rummel et al, 2013) commonly followed by 24 months rituximab maintenance (Salles et al, 2008). Anthracycline, purine analogue, and alkylator combination are used at relapse and younger patients may have remissions consolidated with autologous or allogeneic stem-cell transplantation (alloSCT) (Kothari et al, 2014). Relapsed or refractory (R/R) FL in patients unfit for transplantation or post-transplantation is incurable, and remains an unmet need

Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial (“real-world”) patients, aged 16–59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18–59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy

Apoptosis Inducing Effect of Plumbagin on Colonic Cancer Cells Depends on Expression of COX-2

Plumbagin, a quinonoid found in the plants of the Plumbaginaceae, possesses medicinal properties. In this study we investigated the anti-proliferative and apoptotic activity of plumbagin by using two human colonic cancer cell lines, HT29 and HCT15. IC50 of Plumbagin for HCT15 and HT29 cells (22.5 µM and 62.5 µM, respectively) were significantly different. To study the response of cancer cells during treatment strategies, cells were treated with two different concentrations, 15 µM, 30 µM for HCT15 and 50 µM, 75 µM for HT29 cells. Though activation of NFκB, Caspases-3, elevated levels of TNF-α, cytosolic Cytochrome C were seen in both HCT15 cells HT29 treated with plumbagin, aberrant apoptosis with decreased level of pEGFR, pAkt, pGsk-3β, PCNA and Cyclin D1was observed only in 15 µM and 30 µM plumbagin treated HCT15 and 75 µM plumbagin treated HT29 cells. This suggests that plumbagin induces apoptosis in both HCT15 cells and HT29 treated, whereas, proliferation was inhibited only in 15 µM and 30 µM plumbagin treated HCT15 and 75 µM plumbagin treated HT29 cells, but not in 50 µM plumbagin treated HT29 cells. Expression of COX-2 was decreased in 75 µM plumbagin treated HT29 cells when compared to 50 µM plumbagin treated HT29 cells, whereas HCT15 cells lack COX. Hence the observed resistance to induction of apoptosis in 50 µM plumbagin treated HT29 cells are attributed to the expression of COX-2. In conclusion, plumbagin induces apoptosis in colonic cancer cells through TNF-α mediated pathway depending on expression of COX-2 expression

Results of a United Kingdom real-world study of polatuzumab vedotin, bendamustine, and rituximab for relapsed/refractory DLBCL

The addition of polatuzumab vedotin to bendamustine and rituximab (Pola-BR) has been shown to improve overall survival (OS) in stem cell transplant (SCT)-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). It is also increasingly used as bridging to CAR T-cell therapy (CAR-T). We retrospectively analysed the efficacy of Pola-BR in 133 patients at 28 UK institutions. Treatment intent was bridging to CAR-T for N=40, re-induction with planned SCT for N=13 and stand-alone treatment for N=78. The overall response rate (ORR) was 57.0% (complete response (CR) 32.8%). After median 7.7 months follow-up, median PFS and OS were 4.8 months and 8.2 months respectively. For stand-alone treatment shortened PFS was associated with bulk disease (>7.5cm) (HR 2.32 (95% CI 1.23-4.38), p=0.009), >1 prior treatment (HR 2.17 (95% CI 1.19-3.95), p=0.01) and refractoriness to the last treatment (HR 3.48 (95% CI 1.79-6.76), p<0.001). For CAR-T bridging the ORR was 42.1% (CR 18.4%) and for treatment after CAR-T failure the ORR was 43.8% (CR 18.8%). These data demonstrate efficacy for Pola-BR as a treatment for SCT-ineligible patients with R/R DLBCL, help to delineate which patients may benefit most, and provide preliminary evidence of efficacy as bridging to CAR-T and after CAR-T failure