MR image-based measurement of rates of change in volumes of brain structures. Part II: Application to a study of Alzheimer's disease and normal aging

We present global and regional rates of brain atrophy measured on serially acquired Tl-weighted brain MR images for a group of Alzheimer's disease (AD) patients and age-matched normal control (NC) subjects using the analysis procedure described in Part I. Three rates of brain atrophy: the rate of atrophy in the cerebrum, the rate of lateral ventricular enlargement and the rate of atrophy in the region of temporal lobes, were evaluated for 14 AD patients and 14 age-matched NC subjects. All three rates showed significant differences between the two groups. However, the greatest separation of the two groups was obtained when the regional rates were combined. This application has demonstrated that rates of brain atrophy, especially in specific regions of the brain, based on MR images can provide sensitive measures for evaluating the progression of AD. These measures will be useful for the evaluation of therapeutic effects of novel therapies for AD.

A reproducible method for automated extraction of brain volumes from 3D human head MR images

An automated method for extracting brain volumes from three commonly acquired three-dimensional (3D) MR images (proton density, T1 weighted, and T2-weighted) of the human head is described. The procedure is divided into four levels: preprocessing, segmentation, scalp removal, and postprocessing. A user-provided reference point is the sole operator-dependent input required. The method's parameters were first optimized and then fixed and applied to 30 repeat data sets from 15 normal older adult subjects to investigate its reproducibility. Percent differences between total brain volumes (TBVs) for the subjects' repeated data sets ranged from .5% to 2.2%. We conclude that the method is both robust and reproducible and has the potential for wide application.

The evolutionary history of termites as inferred from 66 mitochondrial genomes

Termites have colonized many habitats and are among the most abundant animals in tropical ecosystems, which they modify considerably through their actions. The timing of their rise in abundance and of the dispersal events that gave rise to modern termite lineages is not well understood. To shed light on termite origins and diversification, we sequenced the mitochondrial genome of 48 termite species and combined them with 18 previously sequenced termite mitochondrial genomes for phylogenetic and molecular clock analyses using multiple fossil calibrations. The 66 genomes represent most major clades of termites. Unlike previous phylogenetic studies based on fewer molecular data, our phylogenetic tree is fully resolved for the lower termites. The phylogenetic positions of Macrotermitinae and Apicotermitinae are also resolved as the basal groups in the higher termites, but in the crown termitid groups, including Termitinae + Syntermitinae + Nasutitermitinae + Cubitermitinae, the position of some nodes remains uncertain. Our molecular clock tree indicates that the lineages leading to termites and Cryptocercus roaches diverged 170 Ma (153-196 Ma 95% confidence interval [CI]), that modern Termitidae arose 54 Ma (46-66 Ma 95% CI), and that the crown termitid group arose 40 Ma (35-49 Ma 95% CI). This indicates that the distribution of basal termite clades was influenced by the final stages of the breakup of Pangaea. Our inference of ancestral geographic ranges shows that the Termitidae, which includes more than 75% of extant termite species, most likely originated in Africa or Asia, and acquired their pantropical distribution after a series of dispersal and subsequent diversification events.

Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins

Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (∆8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent ∆8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H2O2. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of ∆8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) and UTH1, present on chromosome XI. Coexpression of these genes in ∆8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation of CCP1 and UTH1 via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress.

Vanquishing the'Patent Trolls'

Patent law provides exclusive rights to exploit scientific inventions, which are novel, inventive, and useful. The regime is intended to promote innovation, investment in research and development, and access to scientific information. In recent times, there have been concerns that the patent system has been abused by opportunistic companies known by the phrase “patent trolls”. It has been alleged that such entities have stunted innovation and spurred unnecessary patent litigation. Adam Jaffe and Josh Lerner discuss such pathologies of patent law in their book, Innovation and Its Discontents: How our Broken Patent System is Endangering Innovation and Progress, and What To Do About It. James Bessen and Michael Meurer have addressed such concerns in their recent text, Patent Failure: How Judges, Bureaucrats, and Lawyers Put Innovators at Risk. There have been particular fears about the rise of “patent trolls” in the field of information technology. Peter Dekin, an assistant general counsel at Intel, used the phrase “patent troll” to describe firms, which acquired patents only to extract settlements from companies on dubious infringement claims.

Crowning of dibenzosilole with a naphthalenediimide functional group to prepare an electron acceptor for organic solar cells

A novel, solution-processable non-fullerene electron acceptor 9,9′-(5,5-dioctyl-5H-dibenzo [b,d]silole-3,7-diyl)bis(2,7-dioctyl-4-(octylamino)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone) (B3) based on dibenzosilole and naphthalenediimide building blocks was designed, synthesized, characterized and successfully used in a bulk-heterojunction organic solar cell. B3 displayed excellent solubility, thermal stability and acquired electron energy levels matching with those of archetypal donor polymer poly(3-hexylthiophene). Solution-processable bulk-heterojunction devices afforded 1.16% power conversion efficiency with a high fill factor of 53%. B3 is the first example in the literature using this design principle, where mild donor units at the peripheries of end-capped naphthalenediimide units tune solubility and optical energy levels simultaneously.

Knowledge transfer through a transnational program partnership between Indonesian and Australian universities

As transnational programs are often advocated as a knowledge transfer opportunity between the partner universities, this case study investigated the knowledge transfer (KT) processes between Indonesian and Australian universities through an undergraduate transnational program partnership (TPP). An inter-organisational KT theoretical framework from the business sector was adapted and used to guide the study. The data were generated through semi-structured interviews with key university officers and document analysis from two partner universities. Based on the thematic analysis of the data, the findings demonstrated that the curriculum mapping process facilitated KT. However, different intentions of the partner universities in establishing the program led to declining interest to conduct more KT when expectations were not met. The Indonesian university’s existing knowledge, acquired from other sources through processes that were serendipitous and based on individual lecturers’ personal experience, meant that KT opportunities through the TPP were not always pursued despite written agreement to exchange knowledge with the Australian partner. While KT most evidently resulted in institutional capacity development for the Indonesian university’s school that managed the TPP, dissemination of knowledge to other units within the university was more challenging due to communication problems between the units. Hence, other universities seeking to conduct KT through TPPs need to understand each partner university's intention in establishing the partnerships, identify the institutions' needs before seeking knowledge input from the partner university and improve the communication between and within the universities for sustainable benefits.

Deathbed instructions and the assessment of capacity: A practical perspective

The assessment of capacity in the context of wills and advance care planning is a challenging task for modern practitioners with the increase in mentally disabling conditions, such as acquired brain injury. This challenge is only heightened in the situation where the assessment occurs at the client’s deathbed as there are the added elements of urgency, and emotional upheaval at the impending death of a loved one. This situation poses a minefield of problems a legal practitioner should be aware of, involving not only the assessment process but also potential professional liability issues. This presentation will address the practical considerations a legal professional should take into account when in this situation. We will focus on two discrete situations and the issues arising from them: first, where there has been an acquired brain injury and legal capacity is in question; and second, where a spinal injury has occurred which does not affect capacity, rather results in the inability to use conventional forms of communication to communicate his/her instructions. We will examine these case studies with a view to proposing a best practice model for legal practitioners when assessing capacity in this context.

The doctrine of necessity and the detention and restraint of people with intellectual impairment: Is there any justification?

In Australia, the legal basis for the detention and restraint of people with intellectual impairment is ad hoc and unclear. There is no comprehensive legal framework that authorises and regulates the detention of, for example, older people with dementia in locked wards or in residential aged care, people with disability in residential services or people with acquired brain injury in hospital and rehabilitation services. This paper focuses on whether the common law doctrine of necessity (or its statutory equivalents) should have a role in permitting the detention and restraint of people with disabilities. Traditionally, the defence of necessity has been recognised as an excuse, where the defendant, faced by a situation of imminent peril, is excused from the criminal or civil liability because of the extraordinary circumstances they find themselves in. In the United Kingdom, however, in In re F (Mental Patient: Sterilisation) and R v Bournewood Community and Mental Health NHS Trust, ex parte L, the House of Lords broadened the defence so that it operated as a justification for treatment, detention and restraint outside of the emergency context. This paper outlines the distinction between necessity as an excuse and as a defence, and identifies a number of concerns with the latter formulation: problems of democracy, integrity, obedience, objectivity and safeguards. Australian courts are urged to reject the United Kingdom approach and retain an excuse-based defence, as the risks of permitting the essentially utilitarian model of necessity as a justification are too great.

Regional and seasonal variation in airborne grass pollen levels between cities of Australia and New Zealand

Although grass pollen is widely regarded as the major outdoor aeroallergen source in Australia and New Zealand (NZ), no assemblage of airborne pollen data for the region has been previously compiled. Grass pollen count data collected at 14 urban sites in Australia and NZ over periods ranging from 1 to 17 years were acquired, assembled and compared, revealing considerable spatiotemporal variability. Although direct comparison between these data is problematic due to methodological differences between monitoring sites, the following patterns are apparent. Grass pollen seasons tended to have more than one peak from tropics to latitudes of 37°S and single peaks at sites south of this latitude. A longer grass pollen season was therefore found at sites below 37°S, driven by later seasonal end dates for grass growth and flowering. Daily pollen counts increased with latitude; subtropical regions had seasons of both high intensity and long duration. At higher latitude sites, the single springtime grass pollen peak is potentially due to a cooler growing season and a predominance of pollen from C3 grasses. The multiple peaks at lower latitude sites may be due to a warmer season and the predominance of pollen from C4 grasses. Prevalence and duration of seasonal allergies may reflect the differing pollen seasons across Australia and NZ. It must be emphasized that these findings are tentative due to limitations in the available data, reinforcing the need to implement standardized pollen-monitoring methods across Australasia. Furthermore, spatiotemporal differences in grass pollen counts indicate that local, current, standardized pollen monitoring would assist with the management of pollen allergen exposure for patients at risk of allergic rhinitis and asthma. © 2015 Springer Science+Business Media Dordrecht

Molecular mimicry: Can epitope mimicry induce autoimmune disease?

Mimicry of host antigens by infectious agents may induce cross-reactive autoimmune responses to epitopes within host proteins which, in susceptible individuals, may tip the balance of immunological response versus tolerance toward response and subsequently lead to autoimmune disease. Epitope mimicry may indeed be involved in the pathogenesis of several diseases such as post-viral myocarditis or Chagas disease, but for many other diseases in which it has been implicated, such as insulin-dependent diabetes mellitis or rheumatoid arthritis, convincing evidence is still lacking. Even if an epitope mimic can support a cross-reactive T or B cell response in vitro, its ability to induce an autoimmune disease in vivo will depend upon the appropriate presentation of the mimicked host antigen in the target tissue and, in the case of T cell mimics, the ability of the mimicking epitope to induce a proliferative rather than anergizing response upon engagement of the MHC-peptide complex with the T cell receptor. B cell presentation of mimicking foreign antigen to T cells is a possible mechanism for instigating an autoimmune response to self antigens that in turn can lead to autoimmune disease under particular conditions of antigen presentation, secondary signalling and effector cell repertoire. In this review evidence in support of epitope mimicry is examined in the light of the necessary immunological considerations of the theory.

The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood

Bone mass acquired during childhood is the primary determinant of adult bone mineral density (BMD) and osteoporosis risk. Bone accrual is subject to genetic influences. Activating and inactivating LRP5 gene mutations elicit extreme bone phenotypes, while more common LRP5 polymorphisms are associated with normal variation of BMD. Our aim was to test the hypothesis that LRP5 gene polymorphisms influence bone mass acquisition during childhood. The association between LRP5 gene polymorphisms and bone size and mineralization was examined in 819 unrelated British Caucasian children (n = 429 boys) aged 9 years. Height, weight, pubertal status (where available), total-body and spinal bone area, bone mineral content (BMC), BMD, and area-adjusted BMC (aBMC) were assessed. Dual-energy X-ray absorptiometry (DXA)-gene associations were assessed by linear regression, with adjustment for age, gender, pubertal status, and body size parameters. There were 140, 79, 12, and 2 girls who achieved Tanner stages I-IV, respectively, and 179 and 32 boys who achieved Tanner stages I and II, respectively. The rs2306862 (N740N) coding polymorphism in exon 10 of the LRP5 gene was associated with spinal BMD and aBMC (each P = 0.01) and total-body BMD and aBMC (P = 0.04 and 0.03, respectively). Adjusting for pubertal stage strengthened associations between this polymorphism and spinal BMD and aBMC (P = 0.01 and 0.002, respectively). Individuals homozygous for the T allele had greater spinal BMD and aBMC scores than those homozygous for the C allele. A dose effect was apparent as the mean spinal BMD and aBMC of heterozygous TC individuals were intermediate between those of their TT and CC counterparts. The N740N polymorphism in exon 10 of LRP5 was associated with spinal BMD and aBMC in pre- and early pubertal children. These results indicate that LRP5 influences volumetric bone density in childhood, possibly through effects on trabecular bone formation.

Critical risk factors affecting the implementation of PPP waste-to-energy projects in China

Since 2003, Mainland China has been promoting the public–private partnership (PPP) procurement model in the waste-to-energy incineration sector to reduce the waste burying rate and improve environmental quality. Five critical risk factors (CRFs) that affect the construction and operation of waste-to-energy incineration projects have been identified from real-life risk events of 14 PPP waste-to-energy incineration plants through content analysis. These risk factors are insufficient waste supply, disposal of non-licensed waste, environmental risk, payment risk, and lack of supporting infrastructure. A recently completed PPP waste-to-energy incineration plant, the Shanghai Tianma project, was investigated to learn from the effective management of CRFs. First-hand data about the Shanghai Tianma project was collected, with a focus on project negotiation and concession agreement. Lessons learned about risk management were acquired. This paper presents a detailed study of the contractual structure, risk sharing scheme, risk response measures to CRFs, and project transfer of a PPP project. The study results will provide governments with management implications to prepare equitable concession agreements and benefit private investors by effectively mitigating and managing risks in future PPP waste-to-energy incineration projects.

Multiview gait biometrics for human identity recognition

We propose a novel multiview fusion scheme for recognizing human identity based on gait biometric data. The gait biometric data is acquired from video surveillance datasets from multiple cameras. Experiments on publicly available CASIA dataset show the potential of proposed scheme based on fusion towards development and implementation of automatic identity recognition systems.

Direct photocatalytic conversion of aldehydes to esters using supported gold nanoparticles under visible light irradiation at room temperature

Visible light can drive esteri fi cation from aldehydes and alcohols using supported gold nanoparticles (Au/Al 2 O 3 ) as photo- catalysts at ambient temperatures. The gold nanoparticles (AuNPs) absorb visible light due to the localized surface plasmon resonance (LSPR) e ff ect, and the conduction electrons of the AuNPs gain the energy of the incident light. The energetic electrons, which concentrate at the NP surface, facilitate the activation of a range of aldehyde and alcohol substrates. The photocatalytic e ffi ciencies strongly depend on the Au loading, particle sizes of the AuNPs, irradiance, and wavelength of the light irradiation. Finally, a plausible reaction mechanism was proposed, and the Au/Al 2 O 3 catalysts can be reused several times without signi fi cantly losing activity. The knowledge acquired in this study may inspire further studies in new e ffi cient recyclable photocatalysts and a wide range of organic synthesis driven by sunlight.