Detecting Early Warning Signs of Delays in Shipbuilding Projects

Ship design and construction involves numerous activities that have to be effectively performed, coordinated and integrated. Various elements can influence the effectiveness of the process due to projects’ large number of stakeholders and the high level of uncertainty. One of the most challenging issues is the delay in product delivery. However, the elements which might result to delay do not develop overnight and there might be early warning signals addressing that the delay, is likely to happen. This paper discusses that by following an early warning procedure, it will be possible to identify possible early warning signs of potential problems which might cause delay. These signs can provide an aid for the project team to take actions before the problem reaches its full impact, thus delaying the project delivery

Transduction of Brain Dopamine Neurons by Adenoviral Vectors Is Modulated by CAR Expression: Rationale for Tropism Modified Vectors in PD Gene Therapy

Gene-based therapy is a new paradigm for the treatment of Parkinson disease (PD) and offers considerable promise for precise targeting and flexibility to impact multiple pathobiological processes for which small molecule agents are not available. Some success has been achieved utilizing adeno-associated virus for this approach, but it is likely that the characteristics of this vector system will ultimately create barriers to progress in clinical therapy. Adenovirus (Ad) vector overcomes limitations in payload size and targeting. The cellular tropism of Ad serotype 5 (Ad5)-based vectors is regulated by the Ad attachment protein binding to its primary cellular receptor, the coxsackie and adenovirus receptor (CAR). Many clinically relevant tissues are refractory to Ad5 infection due to negligible CAR levels but can be targeted by tropism-modified, CAR-independent forms of Ad. Our objective was to evaluate the role of CAR protein in transduction of dopamine (DA) neurons in vivo.Ad5 was delivered to the substantia nigra (SN) in wild type (wt) and CAR transgenic animals. Cellular tropism was assessed by immunohistochemistry (IHC) in the SN and striatal terminals. CAR expression was assessed by western blot and IHC. We found in wt animals, Ad5 results in robust transgene expression in astrocytes and other non-neuronal cells but poor infection of DA neurons. In contrast, in transgenic animals, Ad5 infects SNc neurons resulting in expression of transduced protein in their striatal terminals. Western blot showed low CAR expression in the ventral midbrain of wt animals compared to transgenic animals. Interestingly, hCAR protein localizes with markers of post-synaptic structures, suggesting synapses are the point of entry into dopaminergic neurons in transgenic animals.These findings demonstrate that CAR deficiency limits infection of wild type DA neurons by Ad5 and provide a rationale for the development of tropism-modified, CAR-independent Ad-vectors for use in gene therapy of human PD

Availability and quality of emergency obstetric care in Gambia's main referral hospital: women-users' testimonies

<p>Abstract</p> <p>Background</p> <p>Reduction of maternal mortality ratio by two-thirds by 2015 is an international development goal with unrestricted access to high quality emergency obstetric care services promoted towards the attainment of that goal. The objective of this qualitative study was to assess the availability and quality of emergency obstetric care services in Gambia's main referral hospital.</p> <p>Methods</p> <p>From weekend admissions a group of 30 women treated for different acute obstetric conditions including five main diagnostic groups: hemorrhage, hypertensive disorders, dystocia, sepsis and anemia were purposively selected. In-depth interviews with the women were carried out at their homes within two weeks of discharge.</p> <p>Results</p> <p>Substantial difficulties in obtaining emergency obstetric care were uncovered. Health system inadequacies including lack of blood for transfusion, shortage of essential medicines especially antihypertensive drugs considerably hindered timely and adequate treatment for obstetric emergencies. Such inadequacies also inflated the treatment costs to between 5 and 18 times more than standard fees. Blood transfusion and hypertensive treatment were associated with the largest costs.</p> <p>Conclusion</p> <p>The deficiencies in the availability of life-saving interventions identified are manifestations of inadequate funding for maternal health services. Substantial increase in funding for maternal health services is therefore warranted towards effective implementation of emergency obstetric care package in The Gambia.</p

Use of complementary and alternative medicines by a sample of Turkish women for infertility enhancement: a descriptive study

<p>Abstract</p> <p>Background</p> <p>Infertility patients are a vulnerable group that often seeks a non-medical solution for their failure to conceive. World-wide, women use CAM for productive health, but only a limited number of studies report on CAM use to enhance fertility. Little is known about traditional and religious forms of therapies that are used in relation to conventional medicine in Turkey. We investigated the prevalence and types of complementary and alternative medicine (CAM) used by infertile Turkish women for fertility enhancement.</p> <p>Methods</p> <p>A face-to-face questionnaire inquiring demographic information and types of CAM used for fertility enhancement were completed by hundred infertility patients admitted to a primary care family planning centre in Van, Turkey between January and July 2009.</p> <p>Results</p> <p>The vast majority of infertile women had used CAM at least once for infertility. CAM use included religious interventions, herbal products and recommendations of traditional "hodja's" (faith healers). Of these women, 87.8% were abused in the last 12 months, 36.6% felt not being supported by her partner and 80.5% had never spoken with a physician about CAM.</p> <p>Conclusions</p> <p>Infertile Turkish women use complementary medicine frequently for fertility enhancement and are in need of information about CAM. Religious and traditional therapies are used as an adjunct to, rather than a substitute for, conventional medical therapy. Physicians need to approach fertility patients with sensitivity and should be able to council their patients about CAM accordingly.</p

Designer Gene Delivery Vectors: Molecular Engineering and Evolution of Adeno-Associated Viral Vectors for Enhanced Gene Transfer

Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addressed to enhance the utility of AAV vectors, particularly those based on AAV2, the best characterized AAV serotype. First, altering viral tropism would be advantageous for broadening its utility in various tissue or cell types. In response to this need, vector pseudotyping, mosaic capsids, and targeting ligand insertion into the capsid have shown promise for altering AAV specificity. In addition, library selection and directed evolution have recently emerged as promising approaches to modulate AAV tropism despite limited knowledge of viral structure–function relationships. Second, pre-existing immunity to AAV must be addressed for successful clinical application of AAV vectors. “Shielding” polymers, site-directed mutagenesis, and alternative AAV serotypes have shown success in avoiding immune neutralization. Furthermore, directed evolution of the AAV capsid is a high throughput approach that has yielded vectors with substantial resistance to neutralizing antibodies. Molecular engineering and directed evolution of AAV vectors therefore offer promise for generating ‘designer’ gene delivery vectors with enhanced properties