Building Our Savings: Reduced infrastructure costs from improving building energy efficiency

Meeting Australia's energy needs sustainably will be a major challenge for the next decade. Electricity consumption is forecast to increase by over 20 percent in the next 10 years, while peak electrical demand is increasing even more rapidly, with almost 30 percent growth forecast from 2010 to 2020. Natural gas consumption is forecast to rise by almost 50 percent and gas peak demand is set to increase by around 40 percent by 2020. An unprecedented level of energy sector capital expenditure has been proposed to meet this growth in total and peak demand. Over $46 billion in electricity network infrastructure alone is planned over just the next five years. Electricity generation and gas infrastructure will add significantly to this figure. This unprecedented expenditure is resulting in dramatic increases in consumer energy tariff

The effect of technique on tackle gainline success outcomes in elite level rugby union

Tackling is a major component of rugby union and effective attacking and defensive play are essential for game outcomes. In this study, a number of pre-contact, contact and post-contact tackle characteristics that had an influence on tackle gainline success for the ball carrier and tackler were identified using match video evidence from European Rugby Champions Cup games. A total of 122 front-on tackles and 111 side-on tackles were analysed. For each ball carrier and tackler characteristic, the Odds Ratio and 95% Confidence Interval were calculated based on a gainline success outcome. A Chi-Square and Phi and Cramer’s V calculation was also conducted. A Chi-Square test then identified any statistically significant differences (p < 0.05) for proficiency characteristics between playing position. For both the ball carrier and tackler, tackle characteristics that were indicative of strong and powerful tackle technique such as ‘explosiveness on contact’ and ‘leg drive on contact’ were effective for achieving the desired gainline outcome. Playing position had an influence on only two proficiency characteristics that were statistically significant for gainline success: ‘fending into contact’ for ball carriers and ‘straight back, centre of gravity forward of support base’ for tacklers

Identification of the PS1 Thr147Ile Variant in a Family with Very Early Onset Dementia and Expressive Aphasia

Background: Early onset dementias have variable clinical presentations and are often difficult to diagnose. We established a family pedigree that demonstrated consistent recurrence of very early onset dementia in successive generations. Objective and Method: In order to refine the diagnosis in this family, we sequenced the exomes of two affected family members and relied on discrete filtering to identify disease genes and the corresponding causal variants. Results: Among the 720 nonsynonymous single nucleotide polymorphisms (SNPs) shared by two affected members, we found a C to T transition that gives rise to a Thr147Ile missense substitution in the presenilin 1 (PS1) protein. The presence of this same mutation in a French early-onset Alzheimer’s disease family, other affected members of the family, and the predicted high pathogenicity of the substitution strongly suggest that it is the causal variant. In addition to exceptionally young age of onset, we also observed significant limb spasticity and early loss of speech, concurrent with progression of dementia in affected family members. These findings extend the clinical presentation associated with the Thr147Ile variant. Lastly, one member with the Thr147Ile variant was treated with the PKC epsilon activator, bryostatin, in a compassionate use trial after successful FDA review. Initial improvements with this treatment were unexpectedly clear, including return of some speech, increased attentional focus, ability to swallow, and some apparent decrease in limb spasticity. Conclusions: Our findings confirm the role of the PS1 Thr147Ile substitution in Alzheimer’s disease and expand the clinical phenotype to include expressive aphasia and very early onset of dementia

Global governance approaches to addressing illegal logging: Uptake and lessons learned

One of the most challenging tasks facing development agencies, trade ministries, environmental groups, social activists and forest-focused business interests seeking to ameliorate illegal logging and related timber trade is to identify and nurture promising global governance interventions capable of helping improve compliance to governmental policies and laws at national, subnational and local levels. This question is especially acute for developing countries constrained by capacity challenges and “weak states” (Risse, 2011). This chapter seeks to shed light on this task by asking four related questions: How do we understand the emergence of illegal logging as a matter of global interest? What are the types of global interventions designed to improve domestic legal compliance? How have individual states responded to these global efforts? What are the prospects for future impacts and evolution? We proceed in the following steps. Following this introduction, step two reviews how the problem of “illegal logging” emerged on the international agenda. Step three reviews leading policy interventions that resulted from this policy framing. Step four reviews developments in selected countries/regions around the world according to their place on the global forest products supply chain: consumers (United States, Europe and Australia); middle of supply chain manufacturers (China and South Korea) and producers (Russia; Indonesia; Brazil and Peru; Ghana, Cameroon and the Republic of Congo). We conclude by reflecting on key trends that emerge from this review relevant for understanding the conditions through which legality might make a difference in addressing critical challenges

Live imaging of the immune response to heart injury in larval zebrafish reveals a multi-stage model of neutrophil and macrophage migration

Neutrophils and macrophages are crucial effectors and modulators of repair and regeneration following myocardial infarction, but they cannot be easily observed in vivo in mammalian models. Hence many studies have utilized larval zebrafish injury models to examine neutrophils and macrophages in their tissue of interest. However, to date the migratory patterns and ontogeny of these recruited cells is unknown. In this study, we address this need by comparing our larval zebrafish model of cardiac injury to the archetypal tail fin injury model. Our in vivo imaging allowed comprehensive mapping of neutrophil and macrophage migration from primary hematopoietic sites, to the wound. Early following injury there is an acute phase of neutrophil recruitment that is followed by sustained macrophage recruitment. Both cell types are initially recruited locally and subsequently from distal sites, primarily the caudal hematopoietic tissue (CHT). Once liberated from the CHT, some neutrophils and macrophages enter circulation, but most use abluminal vascular endothelium to crawl through the larva. In both injury models the innate immune response resolves by reverse migration, with very little apoptosis or efferocytosis of neutrophils. Furthermore, our in vivo imaging led to the finding of a novel wound responsive mpeg1+ neutrophil subset, highlighting previously unrecognized heterogeneity in neutrophils. Our study provides a detailed analysis of the modes of immune cell migration in larval zebrafish, paving the way for future studies examining tissue injury and inflammation

Back-illuminated electron multiplying technology: The world&apos;s most sensitive CCD for ultra low-light microscopy

ABSTRACT The back-illuminated Electron Multiplying Charge Coupled Device (EMCCD) camera stands to be one the most revolutionary contributions ever to the burgeoning fields of low-light dynamic cellular microscopy and single molecule detection, combining extremely high photon conversion efficiency with the ability to eliminate the readout noise detection limit. Here, we present some preliminary measurements recorded by a very rapid frame rate version of this camera technology, incorporated into a spinning disk confocal microscopy set-up that is used for fast intracellular calcium flux measurements. The results presented demonstrate the united effects of: (a) EMCCD technology in amplifying the very weak signal from these fluorescently labelled cells above the readout noise detection limit, that they would otherwise be completely lost in; (b) back-thinned CCD technology in maximizing the signal/shot noise ratio from such weak photon fluxes. It has also been shown how this innovative development can offer significant signal improvements over that afforded by ICCD technology. Practically, this marked advancement in detector sensitivity affords benefits such as shorter exposure times (therefore faster frame rates), lower dye concentrations and reduced excitation powers and will remove some of the barriers that have been restricting the development of new innovative low-light microscopy techniques

The broad phenotypic spectrum of 17α-hydroxylase/17,20-lyase (CYP17A1) deficiency: a case series

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterised by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. OBJECTIVE: To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. DESIGN: Case series. PATIENTS AND RESULTS: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr) and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of WT activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. CONCLUSION: Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol has not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity. SIGNIFICANCE STATEMENT: Here we report, supported by careful phenotyping, genotyping and functional analysis, a prismatic case series of patients with congenital adrenal hyperplasia due to 17α-hydroxylase (CYP17A1) deficiency (17OHD). These range in severity from the abolition of function, presenting in early infancy, and unusually mild with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients. These findings will guide improved diagnostic detection of CYP17A1 deficiency

Prevalence of concomitant rheumatologic diseases and autoantibody specificities among racial and ethnic groups in SLE patients

Objective: Leveraging the Manhattan Lupus Surveillance Program (MLSP), a population-based registry of cases of systemic lupus erythematosus (SLE) and related diseases, we investigated the proportion of SLE with concomitant rheumatic diseases, including Sjögren’s disease (SjD), antiphospholipid syndrome (APLS), and fibromyalgia (FM), as well as the prevalence of autoantibodies in SLE by sex and race/ethnicity. Methods: Prevalent SLE cases fulfilled one of three sets of classification criteria. Additional rheumatic diseases were defined using modified criteria based on data available in the MLSP: SjD (anti-SSA/Ro positive and evidence of keratoconjunctivitis sicca and/or xerostomia), APLS (antiphospholipid antibody positive and evidence of a blood clot), and FM (diagnosis in the chart). Results: 1,342 patients fulfilled SLE classification criteria. Of these, SjD was identified in 147 (11.0%, 95% CI 9.2–12.7%) patients with women and non-Latino Asian patients being the most highly represented. APLS was diagnosed in 119 (8.9%, 95% CI 7.3–10.5%) patients with the highest frequency in Latino patients. FM was present in 120 (8.9%, 95% CI 7.3–10.5) patients with non-Latino White and Latino patients having the highest frequency. Anti-dsDNA antibodies were most prevalent in non-Latino Asian, Black, and Latino patients while anti-Sm antibodies showed the highest proportion in non-Latino Black and Asian patients. Anti-SSA/Ro and anti-SSB/La antibodies were most prevalent in non-Latino Asian patients and least prevalent in non-Latino White patients. Men were more likely to be anti-Sm positive. Conclusion: Data from the MLSP revealed differences among patients classified as SLE in the prevalence of concomitant rheumatic diseases and autoantibody profiles by sex and race/ethnicity underscoring comorbidities associated with SLE

Augmentation index assessed by applanation tonometry is elevated in Marfan Syndrome

<p>Abstract</p> <p>Background</p> <p>To examine whether augmentation index (AIx) is increased in Marfan syndrome (MFS) and associated with increased aortic root size, and whether a peripheral-to-central generalised transfer function (GTF) can be applied usefully in MFS.</p> <p>Methods</p> <p>10 MFS patients and 10 healthy controls (matched for sex, age and height) were studied before and after 400 μg sub-lingual GTN. Arterial waveforms were recorded using applanation tonometry. AIx and pulse pressure (PP) were determined for the radial and carotid arteries. Pulse wave velocity (PWV) was measured between carotid and femoral arteries. GTFs were generated to examine the relationship between radial and carotid waveforms.</p> <p>Results</p> <p>AIx was greater in MFS compared to controls at radial (mean -31.4 (SD 14.3)% v -50.2(15.6)%, p = 0.003) and carotid (-7.6(11.2)% v -23.7(12.7)%, p = 0.004) sites. Baseline PP at all measurement sites, and PWV, did not differ between subject groups. Multivariate analysis demonstrated that PWV and carotid AIx were positively correlated with aortic root size (p < 0.001 and p = 0.012 respectively), independent of the presence of MFS. PP was not associated with aortic root size. GTN caused similar decreases in AIx in both controls and patients. Significant differences were found in GTFs between MFS and control subjects, which changed following GTN administration. However, when an independent GTF was used to derive carotid waves from radial waves, no differences were found in the degree of error between MFS and controls.</p> <p>Conclusion</p> <p>AIx is sensitive to the vascular abnormalities present in MFS, and may have a role as an adjunct to measurement of central PP and PWV. Differences between MFS and controls in the nature of the peripheral-to-central GTF are present, although have little effect on the pulse contour.</p