Development of a system model for cost management in low-cost housing projects in Nigeria

Poor project cost performance is one of the vital issues challenging successful construction project delivery particularly in developing countries such as Nigeria. This issue is endemic particularly in Low-cost housing (LcH) projects with adverse effects on delivery, affordability of the target beneficiaries and housing situations in Nigeria. Past studies highlight the relationship between project cost management systems (CMS) and cost performances. However, extensive studies exploring the CMS for LcH project delivery in Nigeria are rare. Apparently, no contemporary attempts are made to proffer appropriate and well-developed systematic solutions indicating possible continuing trends of poor cost management and performances in LcH project delivery. Given this discovery, this research seeks to develop a cost management system model (CMSM) for LcH project delivery in Nigeria. Empirical investigations explore the concepts of LcH project delivery, project cost management system (CMS) and implementation success factors (IMSF). The research leans towards an interpretivism perspective. It adopts a case study strategy and employs a sequential mixed method procedure for data collection and analysis at different phases of the research. A mix of focus group, semi-structured interviews, and questionnaires facilitated data collection and thematic- content analysis and statistical analysis (percentages, relative agreement index, Kruskal-Wallis, and exploratory factor analysis) for data analysis. Research findings reveal that popular CMS employed by the Project Management Teams (PMT) are incapable of delivering effective LcH project cost performances following three key constraints: difficulty to effectively set target cost, plan and perform real-time project cost monitoring and control, creating rooms for variations and overruns. These limitations were traceable to inappropriate use of cost management techniques, process approach alongside 18 implementation barriers. Integrating Target costing, Earn value analysis, a cost- design-control process approach and consideration of three key IMSF namely effective team qualities, effective information and management actions and stable operational environment were identified measures to improve current CMS efficacy. The research findings were used to develop the CMSM and its operational guide employing three modelling techniques: conventional process modelling, interpretive structural modelling (ISM) and the interpretive ranking process (IRP). These modelling techniques enhanced the design and understanding of the contextual relationships between the techniques, process, and IMSF in the CMS. The IRP and ISM used in this study are novel contributions to construction research, particularly in the area of LcH project cost management. The validation of the CMSM shows its capability to facilitate improved project cost management towards effective cost performances of LcH projects. The CMSM will assist the PMT to set effectively, plan, monitor, and control costs in LcH project delivery in Nigeria

Systems thinking and CMM for continuous improvement in the construction industry

Purpose The purpose of this paper is to present a capability maturity model (CMM) developed to implement continuous improvement in small and medium scale construction companies (SMSCC) in Nigeria. Design/methodology/approach A multi-strategy approach involving qualitative studies of SMSCC in Nigeria was conducted. Semi-structured interviews were conducted with purposively selected construction experts in Nigeria to identify variables essential for continuous improvement in SMSCC. Data collected were thematically analysed using NVIVO. Subsequently, a system thinking approach is employed to design and develop the CMM for implementing continuous improvement SMSCC, by exploring possible relationships between the variables established. Findings CMM provided a five-level approach for the inclusion of investigated variables such as team performance; culture; structure; post-project reviews, financial risk management, waste management policy and cost control. These variables are factors leading to continuous improvement in SMSCC, implementable within a six to seven and a half years’ timeline. Practical implications The system thinking model revealed cogent archetypes in the form of reinforcing loops that can be applied in developing the performance of SMSCC. Continuous improvement is feasible. However, it takes time to implement. Further longitudinal studies on the cost of implementing continuous improvement through CMM a knowledge transfer project can be initiated. Originality/value A methodical strategy for enhancing the effectiveness and operations of SMSCC in developing countries can be extracted from the causal loop diagram and the CMM

DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia.

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer\u27s vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease model with broad relevance for further interrogating the genetic etiology of human ciliopathies

Reassortant Avian Influenza Virus (H5N1) in Poultry, Nigeria, 2007

Reassortant Influenza Virus (H5N1) in Poultry, Nigeria, 200

SciClone: Inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy

Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers

Resistance to oestrogen-deprivation therapy is common in oestrogen-receptor-positive (ER+) breast cancer. To better understand the contributions of tumour heterogeneity and evolution to resistance, here we perform comprehensive genomic characterization of 22 primary tumours sampled before and after 4 months of neoadjuvant aromatase inhibitor (NAI) treatment. Comparing whole-genome sequencing of tumour/normal pairs from the two time points, with coincident tumour RNA sequencing, reveals widespread spatial and temporal heterogeneity, with marked remodelling of the clonal landscape in response to NAI. Two cases have genomic evidence of two independent tumours, most obviously an ER− ‘collision tumour', which was only detected after NAI treatment of baseline ER+ disease. Many mutations are newly detected or enriched post treatment, including two ligand-binding domain mutations in ESR1. The observed clonal complexity of the ER+ breast cancer genome suggests that precision medicine approaches based on genomic analysis of a single specimen are likely insufficient to capture all clinically significant information

Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

<p>Abstract</p> <p>Background</p> <p>Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of <it>Cimicifuga dahurica </it>showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of <it>C. dahurica </it>and therefore might eventually be useful in the prevention or treatment of Hepatoma.</p> <p>Methods</p> <p>The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H₂₂hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA <it>in vivo</it>.</p> <p>Results</p> <p>The IC₅₀values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G₀/G₁cell cycle arrest at lower concentration (25 μg/ml), and triggered G₂/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H₂₂tumor in a dose-dependent manner.</p> <p>Conclusion</p> <p>TGA may potentially find use as a new therapy for the treatment of hepatoma.</p