Better cars or older cars?: Assessing CO2 emission reduction potential of passenger vehicle replacement programs

The primary motivation for the vehicle replacement schemes that were implemented in many countries was to encourage the purchase of new cars. The basic assumption of these schemes was that these acquisitions would benefit both the economy and the environment as older and less fuel-efficient cars were scrapped and replaced with more fuel-efficient models. In this article, we present a new environmental impact assessment method for assessing the effectiveness of scrappage schemes for reducing CO2 emissions taking into account the rebound effect, driving behavior for older versus new cars and entire lifecycle emissions for during the manufacturing processes of new cars. The assessment of the Japanese scrappage scheme shows that CO2 emissions would only decrease if users of the scheme retained their new gasoline passenger vehicles for at least 4.7 years. When vehicle replacements were restricted to hybrid cars, the reduction in CO2 achieved by the scheme would be 6-8.5 times higher than the emissions resulting from a scheme involving standard, gasoline passenger vehicles. Cost-benefit analysis, based on the emission reduction potential, showed that the scheme was very costly. Sensitivity analysis showed that the Japanese government failed to determine the optimum, or target, car age for scrapping old cars in the scheme. Specifically, scrapping cars aged 13 years and over did not maximize the environmental benefits of the scheme. Consequently, modifying this policy to include a reduction in new car subsidies, focused funding for fuel-efficient cars, and modifying the target car age, would increase environmental benefits. © 2013 Elsevier Ltd.

Improving the outcomes of foot and ankle surgery through the audit cycle : a case study

The direct costs of managing adverse outcomes from Australian health care are estimated to be $2 billion. The audit cycle is considered an important tool to assist in the preventive management of adverse outcomes.Australian guidelines for audit cycle design allow for comparison of data sets derived from similar surgical specialities. However a lack of data set standardisation inhibits meaningful comparisons of foot and ankle surgical audits. This research will assist development of a best practice model for auditing foot and ankle surgery. Data derived from this model will improve the safety and quality of foot and ankle surgery. The preliminary phase of this process is to identify and understand the attitudes and behaviours of how and why surgeons participate in the audit cycle. A descriptive embedded multiple case study research design is planned to provide an intense focus on a single phenomenon (the audit cycle) within its real life context (clinical governance). The measures to be included in the case study have been identified by the Balanced Patient Safety Measurement Framework. These include: audit and peer review activity, provider attitudes to patient safety, safety learning, action and performance. A purposive sample of 6 to 8 surgeons (units of analysis) from 3 to 4 specialities (cases) will undergo semi-structured interview. This will investigate: current audit tools and processes; attitudes; and behaviours of surgeons to the audit cycle. Similarities in and differences between the units of analysis will indicate which identified measures function as barriers or enablers of the audit cycle. Reliability and validity (external and construct) will be assessed using established methods for case studies. The descriptive embedded multiple case study will reveal how and why foot and ankle surgeons participate in the audit cycle. This will inform further research to improve the outcomes of foot and ankle surgery through development of an audit tool.

Awards before and after the Nobel Prize : a Matthew effect and/or a ticket to one's own funeral?

The primary aim of this descriptive exploration of scientists’ life cycle award patterns is to evaluate whether awards breed further awards and identify researcher experiences after reception of the Nobel Prize. To achieve this goal, we collected data on the number of awards received each year for 50 years before and after Nobel Prize reception by all 1901–2000 Nobel laureates in physics, chemistry, and medicine or physiology. Our results indicate an increasing rate of awards before Nobel reception, reaching the summit precisely in the year of the Nobel Prize. After this pinnacle year, awards drop sharply. This result is confirmed by separate analyses of three different disciplines and by a random-effects negative binomial regression model. Such an effect, however, does not emerge for more recent Nobel laureates (1971–2000). In addition, Nobelists in medicine or physiology generate more awards shortly before and after prize reception, whereas laureates in chemistry attract more awards as time progresses.

Restraint in the age of speed: Protecting vulnerable news sources in the 24/7 global news cycle

As news communication speeds up, investigative journalists have an increasing responsibility to minimise the risk of harm to vulnerable news sources. In addition, the increased longevity and instant global search-ability of news coverage and investigative journalism outputs such as documentaries, places upon journalists an increased responsibility for accuracy since online coverage cannot be easily corrected or retracted. This paper will examine how the risks to a news source and her family were considered and mitigated during the production of a radio documentary and newspaper story about an intended victim of child sacrifice. Pre-publication considerations included the possible risks to the mental health of the news source, the potential physical risk to her children and the risk to future family relationships. To hear the ABC Radio National documentary, A living sacrifice, on 360 Documentaries prior to the conference, see http://www.abc.net.au/radionational/programs/360/a-living-sacrifice/5359744. To read the Sunday Mail newspaper coverage of the story see http://www.couriermail.com.au/news/queensland/susannah-birch-talks-about-her-throat-being-slit-by-her-mother-when-she-was-a-baby/story-fnihsrf2-1226881911465.

Determination of the effect of JO146, a CtHtrA inhibitor, on the chlamydial developmental cycle and persistence

The role of Chlamydia trachomatis HtrA (CtHtrA) for the growth and pathogenesis of this organism is presented. Inhibition of CtHtrA led to loss of infectious progeny in Chlamydia, particularly during heat stress or recovery from penicillin persistence. Isolation of CtHtrA inhibitor resistant mutants identified positive selection for mutants in fatty acid related pathways. Importantly, HtrA inhibition was effective against clinical isolates of C. trachomatis. Thus the findings combined indicate that CtHtrA is an important chlamydial growth factor that has the potential to be targeted for the development of anti-chlamydial drugs in the future.

A low cost demagnetizer with controllable cycle and adjustable level

Demagnetization to zero remanent value or to a predetermined value is of interest to magnet manufacturers and material users. Conventional methods of demagnetization using a varying alternating demagnetizing field, under a damped oscillatory or conveyor system, result in either high cost for demagnetization or large power dissipation. A simple technique using thyristors is presented for demagnetizing the material. Power consumption is mainly in the first two half-cycles of applied voltage. Hence power dissipation is very much reduced. An optimum value calculation for a thyristor triggering angle for demagnetizing high coercive materials is also presented.

Motivation or demotivation of health workers providing maternal health services in rural areas in Vietnam: findings from a mixed-methods study

Background Motivation is an important driver for health professionals to maintain professional competencies, continue in a workforce and contribute to work tasks. While there is some research about motivation in health workers in low to middle income countries, maternal morbidity and mortality remains high in many low and middle income countries and this can be improved by improving the quality of maternal services and the training and skills maintenance of maternal health workers. This study examines the impact of motivation on maintenance of professional competence among maternal health workers in Vietnam using mixed methods. Methods The study consisted of a survey using a self-administered questionnaire of 240 health workers in 5 districts across two Vietnamese provinces and in-depth interviews with 43 health workers and health managers at the commune, district and provincial level to explore external factors that influenced motivation. The questionnaire includes a 23 item motivation instrument based on Kenyan health context, modified for Vietnamese language and culture. Results The 240 responses represented an estimated 95% of the target sample. Multivariate analysis showed that three factors contributed to the motivation of health workers: access to training (β = -0.14, p=0.03), ability to perform key tasks (β = 0.22, p=0.001), and shift schedule (β = -0.13, p=0.05). Motivation was higher in health workers self-identifying as competent or enabled to provide more care activities. Motivation was lower in those who worked more frequent night shifts and those who had received training in the last 12 months. The interviews identified that the latter was because they felt the training was irrelevant to them, and in some cases, they do not have opportunity to practice their learnt skills. The qualitative data also showed other factors relating to service context and organisational management practices contributed to motivation. Conclusions The study demonstrates the importance of understanding the motivations of health workers and the factors that contribute to this and may contribute to more effective management of the health workforce in low and middle income countries.

Beta-Ketoacyl-ACP Synthase I/II from Plasmodium falciparum (PfFabB/F)-Is it B or F?

Condensing enzymes play an important and decisive role in terms of fatty acid composition of any organism. They can be classified as condensing enzymes involved in initiating the cycle and enzymes involved in elongating the initiated fatty acyl chain. In E. coli, two isoforms for the elongation condensing enzymes (FabB and FabF) exists whereas Plasmodium genome contains only one isoform. By in vitro complementation studies in E. coli CY244 cells, we show that PfFabB/ functions like E. coli FabF as the growth of the mutant cells could rescued only in the presence of oleic acid. But unlike bacterial enzyme, PfFabB/F does not increase the cis-vaccenic acid content in the mutant cells upon lowering the growth temperature. This study thus highlights the distinct properties of P. falciparum FabF which sets it apart from E. coli and most other enzymes of this family, described so far.

An effective, economic way of monitoring menstrual cycle hormones in at risk female athletes

PURPOSE: Female athletes, in response to intensive training, competition stress and a lean, athletic physique, are at increased risk of altered hypothalamic-pituitary ovarian (HPO) axis function associated with menstrual cycle disturbance and reduced secretion of the ovarian hormones estrogen and progesterone. Because there is evidence suggesting possible detrimental effects on skeletal health associated with deficiencies in these hormones, a suitable means to asses ovarian hormone concentrations in at risk athletes is needed. The aim of this study was to evaluate a simple, economical means to monitor the ovarian hormone production in athletes, in the setting of intensive training. METHODS: Subjects comprised 14 adolescent rowers, 12 lightweight rowers, and two groups of 10 matched control subjects. Ovarian function was monitored during the competition season by estimation of urinary excretion of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG), enabling the menstrual cycles to be classified as ovulatory or anovulatory. RESULTS: Results indicated 35% and 75% of schoolgirl and lightweight rowers had anovulatory menstrual cycles, respectively. These findings were highlighted by significantly lower excretion of E1G and PdG during phases of intensive training in both the lightweight and schoolgirl rowers, compared with the control subjects. CONCLUSION: It was concluded that the urinary E1G and PdG assays were an effective means to assess the influence of intense training on ovarian hormone concentrations in at risk athletes. It is recommended that this technique be applied more widely as a means of early detection of athletes with low estrogen and progesterone levels, in an attempt to avoid detrimental influences on skeletal health.

Effect of Ethanol Extract of Whole Plant of Trichosanthes cucumerina var. cucumerina L. on Gonadotropins, Ovarian Follicular Kinetics and Estrous Cycle for Screening of Antifertility Activity in Albino Rats

Ethanol extract of whole plant of Trichosanthes cucumerina L. var. cucumerina was evaluated for antiovulatory activity in adult rats. The ethanol extract at the doses 200 and 400mg/kg body weight (orally) affected the normal estrous cycle showing a significant increase in estrus and metestrus phases and decrease in diestrus and proestrus phases. The extract also significantly reduced the number of healthy follicles (Class I-Class VI) and corpora lutea and increased the number of regressing follicles (Stage IA, Stage IB, Stage IIA, and Stage IIB). The protein and glycogen content in the ovaries were significantly reduced in treated rats. The cholesterol level was significantly increased, whereas, the enzyme activities like 3b-HSD and 17b-HSD were significantly inhibited in the ovary of treated rats. Serum FSH and LH levels were significantly reduced in the treated groups were measured by RIA. In acute toxicity test, neither mortality nor change in the behavior or any other physiological activities in mice were observed in the treated groups. In chronic toxicity studies, no mortality was recorded and there were no significant differences in the body and organ weights were observed between controls and treated rats. Hematological analysis showed no significant differences in any of the parameters examined (RBC, WBC count and Hemoglobin estimation). These observations showed the antiovulatory activity of ethanol extract of whole plant of Trichosanthes cucumerina L. var. cucumerina in female albino rats.

Refining the process of agent selection through understanding plant demography and plant response to herbivory

Understanding plant demography and plant response to herbivory is critical to the selection of effective weed biological control agents. We adopt the metaphor of 'filters' to suggest how agent prioritisation may be improved to narrow our choices down to those likely to be most effective in achieving the desired weed management outcome. Models can serve to capture our level of knowledge (or ignorance) about our study system and we illustrate how one type of modelling approach (matrix models) may be useful in identifying the weak link in a plant life cycle by using a hypothetical and an actual weed example (Parkinsonia aculeata). Once the vulnerable stage has been identified we propose that studying plant response to herbivory (simulated and/or actual) can help identify the guilds of herbivores to which a plant is most likely to succumb. Taking only potentially effective agents through the filter of host specificity may improve the chances of releasing safe and effective agents. The methods we outline may not always lead us definitively to the successful agent(s), but such an empirical, data-driven approach will make the basis for agent selection explicit and serve as testable hypotheses once agents are released.

To reactivate or not to reactivate : Control of KSHV lytic replication is essential for apoptosis in response to p53 restoration

Kaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the causative agent of three human malignancies: Kaposi's sarcoma (KS), Multicentric Castleman's Disease (MCD), and primary effusion lymphoma (PEL). In tumors, KSHV establishes latent infection during which it produces no infectious particles. Latently infected cells can enter the lytic replication cycle, and upon provision of appropriate cellular signals, produce progeny virus. PEL, commonly described in patients with AIDS, represents a diffuse large-cell non-Hodgkin's lymphoma, with median survival time less than six months after diagnosis. As tumor suppressor gene TP53 mutations occur rarely in PEL, the aim of this thesis was to investigate whether non-genotoxic activation of the p53 pathway can eradicate malignant PEL cells. This thesis demonstrates that Nutlin-3, a small-molecule inhibitor of the p53-MDM2 interaction, efficiently restored p53 function in PEL cells, leading to cell cycle arrest and massive apoptosis. Furthermore, we found that KSHV infection activated DNA damage signaling, rendering the cells more sensitive to p53-dependent cell death. We also showed in vivo the therapeutic potential of p53 restoration that led to regression of subcutaneous and intraperitoneal PEL tumor xenografts without adversely affecting normal cells. Importantly, we demonstrated that in a small subset of intraperitoneal PEL tumors, spontaneous induction of viral reactivation dramatically impaired Nutlin-3-induced p53-mediated apoptosis. Accordingly, we found that elevated KSHV lytic transcripts correlated with PEL tumor burden in animals and that inhibition of viral reactivation in vitro restored cytotoxic activity of a small-molecule inhibitor of the p53-MDM2 interaction. Latency provides a unique opportunity for KSHV to escape host immune surveillance and to establish persistent infections. However, to maintain viral reservoirs and spread to other hosts, KSHV must be reactivated from latency and enter into the lytic growth phase. We showed that phosphorylation of nucleolar phosphoprotein nucleophosmin (NPM) by viral cyclin-CDK6 is critical for establishment and maintenance of the KSHV latency. In short, this study provides evidence that the switch between latent phase and lytic replication is a critical step that determines the outcome of viral infection and the pathogenesis of KSHV-induced malignancies. Our data may thus contribute to development of novel targeted therapies for intervention and treatment of KSHV-associated cancers.

The Neurofibromatosis 2 tumor suppressor merlin in cytoskeleton organization and cell cycle regulation

Neurofibromatosis 2 (NF2) is a dominantly inherited disorder, which predisposes to multiple tumours of the nervous system, typically schwannomas and meningiomas. Biallelic inactivation of the NF2 gene occurs both in sporadic and NF2-related schwannomas and in most meningiomas. The NF2 gene product merlin (or schwannomin) is structurally related to the ERM proteins, ezrin, radixin and moesin, which act as molecular linkers between the actin cytoskeleton and the plasma membrane. Merlin is a tumor suppressor that participates in cell cycle regulation. Merlin s phosphorylation status appears to be associated with its tumour suppressor activity, i.e. non-phosphorylated merlin functions as a tumour suppressor, whereas protein phosphorylation results in loss of functional activity. This thesis study was initiated to investigate merlin s role as a tumor suppressor and growth inhibitor. These studies show, that like many other tumor suppressors, also merlin is targeted to the nucleus at some stages of the cell cycle. Merlin s nuclear localization is regulated by cell cycle phase, contact inhibition and adhesion. In addition, a potential nuclear binding partner for merlin was identified, Human Enhancer of Invasion 10 (HEI10), a cyclin B interacting protein. Many tumor suppressors interact with microtubules and this thesis work shows that also merlin colocalizes with microtubules in mitotic structures. Merlin binds microtubules directly, and increases their polymerization in vitro and in vivo. In addition, primary mouse Schwann cells lacking merlin displays disturbed microtubule cytoskeleton. Fourth part of this thesis work began from the notion that PKA phosphorylates an unidentified site from the merlin N-terminus. Our studies show that serine 10 is a target for PKA and modulation of this residue regulates cytoskeletal organization, lamellipodia formation and cell migration. In summary, this thesis work shows that merlin s role is much more versatile than previously thought. It has a yet unidentified role in the nucleus and it participates in the regulation of both microtubules and the actin cytoskeleton. These studies have led to a better understanding of this enigmatic tumor suppressor, which eventually will aid in the design of specific drugs for the NF2 disease.

Defects in tricarboxylic acid cycle enzymes Fumarate hydratase and Succinate dehydrogenase in cancer

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a recently characterized cancer syndrome which predisposes to cutaneous and uterine leiomyomas as well as renal cell carcinoma (RCC). Uterine leiomyosarcoma (ULMS) has also been observed in certain Finnish HLRCC families. The predisposing gene for this syndrome, fumarate hydratase (FH), was identified in 2002. The well-known function of FH is in the tricarboxylic acid cycle (TCAC) in the energy metabolism of cells. As FH is a novel cancer gene, the role of FH mutations in tumours is in general unknown. Similarly, the mechanisms through which defective FH is associated with tumourigenesis are unclear. The loss of a wild type allele has been observed in virtually all HLRCC patients tumours and the FH enzyme activities are either totally lost or remarkably reduced in the tissues of mutation carrier patients. Therefore, FH is assumed to function as a tumour suppressor. Mutations in genes encoding subunits of other TCAC enzyme SDH have also been reported recently in tumours: mutations in SDHB, SDHC, and SDHD genes predispose to paraganglioma and pheochromocytoma. In the present study, mutations in the SDHB gene were observed to predispose to RCC. This was the first time that mutations in SDHB have been detected in extra-paraganglial tumours. Two different SDHB mutations were observed in two unrelated families. In the first family, the index patient was diagnosed with RCC at the age of 24 years. Additionally, his mother with a paraganglioma (PGL) of the heart and his maternal uncle with lung cancer were both carriers of the mutation. The RCC of the index patient and the PGL of his mother showed LOH. In the other family, an SDHB mutation was detected in two siblings who were both diagnosed with RCC at the ages of 24 and 26 years. Both of the siblings also suffered PGL. All these tumours showed LOH. Therefore, we concluded that mutations in SDHB predispose also for RCC in certain families. Several tumour types were analysed for FH mutations to define the role of FH mutations in these tumour types. In addition, patients with a putative cancer phenotype were analysed to identify new HLRCC families. Three FH variants were detected, of which two were novel. One of the variants was observed in a patient diagnosed with ULMS at the age of 41 years. However, LOH was not detected in the tumour tissue. The FH enzyme activity of the mutated protein was clearly reduced, being 43% of the activity of the normal protein. Together with the results from an earlier study we calculated that the prevalence of FH mutations in Finnish non-syndromic ULMS is around 2.4%. Therefore, FH mutations seem to have a minor role in the pathogenesis on non-syndromic ULMS. Two other germline variants were detected in a novel tumour type, ovarian mucinous cystadenoma. However, tumour tissues of the patients were not available for LOH studies and therefore LOH status remained unclear. Therefore, it is possible that FH mutations predispose also for ovarian tumours but further studies are needed to verify this result. A novel variant form of the FH gene (FHv) was identified and characterized in more detail. FHv contains an alternative first exon (1b), which appeared to function as 5 UTR sequence. The translation of FHv is initiated in vitro from exons two and three. The localization of FHv is both cytosolic and nuclear, in contrast to the localization of FH in mitochondria. FHv is expressed at low levels in all human tissues. Interestingly, the expression was induced after heat shock treatment and in chronic hypoxia. Therefore, FHv might have a role e.g. in the adaptation to unfavourable growth conditions. However, this remains to be elucidated.