Therapeutic options for metastatic castration resistant prostate cancer : has the situation improved?

Limited treatment options for Castration Resistant Prostate Cancer (CRPC) still remain a major challenge. Despite therapeutic advances, most patients with malignant PCa have a poor prognosis. Since the year 2000, we have rapidly expanded our understanding of the molecular mechanisms underlying CRPC and this has led to an unprecedented number of new drug approvals within a short span of time. Recently, four new agents namely Abiraterone Acetate, Enzalutamide, Cabazitaxel, and Radium-223 have been shown to be effective in the post-chemotherapy setting in CRPC. The continued dependency of CRPC on androgen synthesis has seen the development of a number of new anti-androgen therapies, with abiraterone acetate and Enzalutamide being the most promising discoveries. Immunotherapeutic approaches have also found their niche in PCa with Sipuleucel-T shown to be effective in minimally asymptomatic CRPC. Research focussed on bone-targeting therapies has witnessed the arrival of promising new drugs with Denosumab and Radium-223 displaying improved survival of patients with CRPC. This review briefly discusses the findings and limitations from ongoing and completed clinical trials of novel treatments and regimens. In addition, potential mechanisms of therapy resistance and future challenges are discussed.

Power quality improvements in low voltage distribution networks containing distributed energy resources

In this thesis various schemes using custom power devices for power quality improvement in low voltage distribution network are studied. Customer operated distributed generators makes a typical network non-radial and affect the power quality. A scheme considering different algorithm of DSTATCOM is proposed for power circulation and islanded operation of the system. To compensate reactive power overflow and facilitate unity power factor, a UPQC is introduced. Stochastic analysis is carried out for different scenarios to get a comprehensive idea about a real life distribution network. Combined operation of static compensator and voltage regulator is tested for the optimum quality and stability of the system.

High and low fear phenotypes show differences in phosphorylated (p44/42 ERK) MAPK-expressing neurons in the lateral amygdala

Post traumatic stress disorder (PTSD) is a serious medical condition effecting both military and civilian populations. While its etiology remains poorly understood it is characterized by high and prolonged levels of fear responding. One biological unknown is whether individuals expressing high or low conditioned fear memory encode the memory differently and if that difference underlies fear response. In this study we examined cellular mechanisms that underlie high and low conditioned fear behavior by using an advanced intercrossed mouse line (B6D2F1) selected for high and low Pavlovian fear response. A known requirement for consolidation of fear memory, phosphorylated mitogen activated protein kinase (p44/42 (ERK) MAPK (pMAPK)) in the lateral amygdala (LA) is a reliable marker of fear learning-related plasticity. In this study, we asked whether high and low conditioned fear behavior is associated with differential pMAPK expression in the LA and if so, is it due to an increase in neurons expressing pMAPK or increased pMAPK per neuron. To examine this, we quantified pMAPK-expressing neurons in the LA at baseline and following Pavlovian fear conditioning. Results indicate that high fear phenotype mice have more pMAPK-expressing neurons in the LA. This finding suggests that increased endogenous plasticity in the LA may be a component of higher conditioned fear responses and begins to explain at the cellular level how different fear responders encode fear memories. Understanding how high and low fear responders encode fear memory will help identify novel ways in which fear-related illness risk can be better predicted and treated.

The origin of cyclical high- and low-Cr basalts with continental crust trace element signatures in the Kalkarindji Large Igneous Province

The 510 million year old Kalkarindji Large Igneous Province correlates in time with the first major extinction event after the Cambrian explosion of life. Large igneous provinces correlate with all major mass extinction events in the last 500 million years. The genetic link between large igneous provinces and mass extinction remains unclear. My work is a contribution towards understanding magmatic processes involved in the generation of Large Igneous Provinces. I concentrate on the origin of variation in Cr in magmas and have developed a model in which high temperature melts intrude into and assimilate large amounts of upper continental crust.

The rise of low-cost sensing for managing air pollution in cities

Ever growing populations in cities are associated with a major increase in road vehicles and air pollution. The overall high levels of urban air pollution have been shown to be of a significant risk to city dwellers. However, the impacts of very high but temporally and spatially restricted pollution, and thus exposure, are still poorly understood. Conventional approaches to air quality monitoring are based on networks of static and sparse measurement stations. However, these are prohibitively expensive to capture tempo-spatial heterogeneity and identify pollution hotspots, which is required for the development of robust real-time strategies for exposure control. Current progress in developing low-cost micro-scale sensing technology is radically changing the conventional approach to allow real-time information in a capillary form. But the question remains whether there is value in the less accurate data they generate. This article illustrates the drivers behind current rises in the use of low-cost sensors for air pollution management in cities, whilst addressing the major challenges for their effective implementation.

The mechanical and inflammatory low back pain (MIL) index: development and validation

Abstract Background The purpose of this study was the development of a valid and reliable “Mechanical and Inflammatory Low Back Pain Index” (MIL) for assessment of non-specific low back pain (NSLBP). This 7-item tool assists practitioners in determining whether symptoms are predominantly mechanical or inflammatory. Methods Participants (n = 170, 96 females, age = 38 ± 14 years-old) with NSLP were referred to two Spanish physiotherapy clinics and completed the MIL and the following measures: the Roland Morris Questionnaire (RMQ), SF-12 and “Backache Index” (BAI) physical assessment test. For test-retest reliability, 37 consecutive patients were assessed at baseline and three days later during a non-treatment period. Face and content validity, practical characteristics, factor analysis, internal consistency, discriminant validity and convergent validity were assessed from the full sample. Results A total of 27 potential items that had been identified for inclusion were subsequently reduced to 11 by an expert panel. Four items were then removed due to cross-loading under confirmatory factor analysis where a two-factor model yielded a good fit to the data (χ2 = 14.80, df = 13, p = 0.37, CFI = 0.98, and RMSEA = 0.029). The internal consistency was moderate (α = 0.68 for MLBP; 0.72 for ILBP), test-retest reliability high (ICC = 0.91; 95%CI = 0.88-0.93) and discriminant validity good for either MLBP (AUC = 0.74) and ILBP (AUC = 0.92). Convergent validity was demonstrated through similar but weak correlations between the ILBP and both the RMQ and BAI (r = 0.34, p < 0.001) and the MLBP and BAI (r = 0.38, p < 0.001). Conclusions The MIL is a valid and reliable clinical tool for patients with NSLBP that discriminates between mechanical and inflammatory LBP. Keywords: Low back pain; Psychometrics properties; Pain measurement; Screening tool; Inflammatory; Mechanical

Enhanced preference for high-fat foods following a simulated night shift

Objectives Shift workers are prone to obesity and associated co-morbidities such as diabetes and cardiovascular disease. Sleep restriction associated with shift work results in dramatic endocrine and metabolic effects that predispose shift workers to these adverse health consequences. While sleep restriction has been associated with increased caloric intake, food preference may also play a key role in weight gain associated with shift work. This study examined the impact of an overnight simulated night shift on food preference. Methods Sixteen participants [mean 20.1, standard deviation (SD) 1.4 years; 8 women] underwent a simulated night shift and control condition in a counterbalanced order. On the following morning, participants were provided an opportunity for breakfast that included high- and low-fat food options (mean 64.8% and 6.4% fat, respectively). Results Participants ate significantly more high-fat breakfast items after the simulated night shift than after the control condition [167.3, standard error of the mean (SEM 28.7) g versus 211.4 (SEM 35.6) g; P=0.012]. The preference for high-fat food was apparent among the majority of individuals following the simulated night shift (81%), but not for the control condition (31%). Shift work and control conditions did not differ, however, in the total amount of food or calories consumed. Conclusions A simulated night shift leads to preference for high-fat food during a subsequent breakfast opportunity. These results suggest that food choice may contribute to weight-related chronic health problems commonly seen among night shift workers.

Women at work! evaluating equal employment policies and outcomes in construction

Purpose The purpose of this paper is to examine equal employment policies in Australia’s male-dominated construction industry and categorise the types of activities undertaken against an equal employment typology to identify links to outcomes for women in the form of increased participation and management. Design/methodology/approach To explore the issue of low representation of women in construction through the content analysis of 83 construction organisations’ equal employment opportunity (EEO) reports. Findings This industry is not engaging with equal employment issues and the numbers of women working in the industry and/or management are based on individual decision rather than an institutional commitment to equality in diversity. Research limitations/implications Australian legislation mandates organisational reporting of relevant data and offers public access to this information offering a unique data set. Practical implications An ageing population means that the predominately older male workforce is leaving construction in greater numbers with fewer potential replacements making new labour markets a vital consideration. Social implications Legislation and organisational policies designed to promote EEO for women have existed in numerous countries for decades. One objective of this legislation was to reduce male domination in senior positions and industries/occupations where women were under-represented. Despite this, few women are employed in construction in operational or management roles worldwide. Originality/value This study offers a comprehensive analysis of a male-dominated industry in one jurisdiction rather than a few selected cases and uses a broader rigorous typology for analysis that acknowledges both equal and different treatment options.

Low probability differentials and the cryptanalysis of full-round CLEFIA-128

So far, low probability differentials for the key schedule of block ciphers have been used as a straightforward proof of security against related-key differential analysis. To achieve resistance, it is believed that for cipher with k-bit key it suffices the upper bound on the probability to be 2− k . Surprisingly, we show that this reasonable assumption is incorrect, and the probability should be (much) lower than 2− k . Our counter example is a related-key differential analysis of the well established block cipher CLEFIA-128. We show that although the key schedule of CLEFIA-128 prevents differentials with a probability higher than 2− 128, the linear part of the key schedule that produces the round keys, and the Feistel structure of the cipher, allow to exploit particularly chosen differentials with a probability as low as 2− 128. CLEFIA-128 has 214 such differentials, which translate to 214 pairs of weak keys. The probability of each differential is too low, but the weak keys have a special structure which allows with a divide-and-conquer approach to gain an advantage of 27 over generic analysis. We exploit the advantage and give a membership test for the weak-key class and provide analysis of the hashing modes. The proposed analysis has been tested with computer experiments on small-scale variants of CLEFIA-128. Our results do not threaten the practical use of CLEFIA.

Buy low, sell high

We consider online trading in a single security with the objective of getting rich when its price ever exhibits a large upcrossing, without risking bankruptcy. We investigate payoff guarantees that are expressed in terms of the extremity of the upcrossings. We obtain an exact and elegant characterisation of the guarantees that can be achieved. Moreover, we derive a simple canonical strategy for each attainable guarantee.

Critical literacy finds a 'place': Writing and social action in a low-income Australian grad 2/3 classroom

In a study of socioeconomically disadvantaged children's acquisition of school literacies, a university research team investigated how a group of teachers negotiated critical literacies and explored notions of social power with elementary children in a suburban school located in an area of high poverty. Here we focus on a grade 2/3 classroom where the teacher and children became involved in a local urban renewal project and on how in the process the children wrote about place and power. Using the students' concerns about their neighborhood, the teacher engaged her class in a critical literacy project that not only involved a complex set of literate practices but also taught the children about power and the possibilities for local civic action. In particular, we discuss examples of children's drawing and writing about their neighborhoods and their lives. We explore how children's writing and drawing might be key elements in developing "critical literacies" in elementary school settings. We consider how such classroom writing can be a mediator of emotions, intellectual and academic learning, social practice, and political activism.

The David and Goliath principle: Cultural, ideological, and attitudinal underpinnings of the normative protection of low-status groups from criticism

Two studies documented the “David and Goliath” rule—the tendency for people to perceive criticism of “David” groups (groups with low power and status) as less normatively permissible than criticism of “Goliath” groups (groups with high power and status). The authors confirmed the existence of the David and Goliath rule across Western and Chinese cultures (Study 1). However, the rule was endorsed more strongly in Western than in Chinese cultures, an effect mediated by cultural differences in power distance. Study 2 identified the psychological underpinnings of this rule in an Australian sample. Lower social dominance orientation (SDO) was associated with greater endorsement of the rule, an effect mediated through the differential attribution of stereotypes. Specifically, those low in SDO were more likely to attribute traits of warmth and incompetence to David versus Goliath groups, a pattern of stereotypes that was related to the protection of David groups from criticism.

Options for rehabilitation in interlock programs

This report examines the effectiveness of national and international programs that treat and rehabilitate drivers with alcohol dependence and the criteria used to approve the removal of interlocks. The project recommends a stepped care model which requires all participants to attend education and screening and then requires participants who fail to change their behaviour to attend increasingly intensive rehabilitation programs. Failure to complete an interlock program could result in participants having their licence revoked. This project was designed to inform action 36(d) of the National Road Safety Strategy 2011-2020: Investigate the option of requiring demonstrated rehabilitation from alcohol dependence before removal of interlock conditions.

First-principle engineering magnetism in low-dimensional boron nitride materials

Nanotubes and nanosheets are low-dimensional nanomaterials with unique properties that can be exploited for numerous applications. This book offers a complete overview of their structure, properties, development, modeling approaches, and practical use. It focuses attention on boron nitride (BN) nanotubes, which have had major interest given their special high-temperature properties, as well as graphene nanosheets, BN nanosheets, and metal oxide nanosheets. Key topics include surface functionalization of nanotubes for composite applications, wetting property changes for biocompatible environments, and graphene for energy storage applications

The combination of plant-expressed cellobiohydrolase and low dosages of cellulases for the hydrolysis of sugar cane bagasse

Background The expression of biomass-degrading enzymes (such as cellobiohydrolases) in transgenic plants has the potential to reduce the costs of biomass saccharification by providing a source of enzymes to supplement commercial cellulase mixtures. Cellobiohydrolases are the main enzymes in commercial cellulase mixtures. In the present study, a cellobiohydrolase was expressed in transgenic corn stover leaf and assessed as an additive for two commercial cellulase mixtures for the saccharification of pretreated sugar cane bagasse obtained by different processes. Results Recombinant cellobiohydrolase in the senescent leaves of transgenic corn was extracted using a simple buffer with no concentration step. The extract significantly enhanced the performance of Celluclast 1.5 L (a commercial cellulase mixture) by up to fourfold on sugar cane bagasse pretreated at the pilot scale using a dilute sulfuric acid steam explosion process compared to the commercial cellulase mixture on its own. Also, the extracts were able to enhance the performance of Cellic CTec2 (a commercial cellulase mixture) up to fourfold on a range of residues from sugar cane bagasse pretreated at the laboratory (using acidified ethylene carbonate/ethylene glycol, 1-butyl-3-methylimidazolium chloride, and ball-milling) and pilot (dilute sodium hydroxide and glycerol/hydrochloric acid steam explosion) scales. We have demonstrated using tap water as a solvent (under conditions that mimic an industrial process) extraction of about 90% recombinant cellobiohydrolase from senescent, transgenic corn stover leaf that had minimal tissue disruption. Conclusions The accumulation of recombinant cellobiohydrolase in senescent, transgenic corn stover leaf is a viable strategy to reduce the saccharification cost associated with the production of fermentable sugars from pretreated biomass. We envisage an industrial-scale process in which transgenic plants provide both fibre and biomass-degrading enzymes for pretreatment and enzymatic hydrolysis, respectively.