Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy in KRAS Wild-Type Patients

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit. KRAS mutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction of KRAS wild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation of BRAF, NRAS, PIK3CA, and PTEN status could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

A right to respond? Monopolisation of 'voice' in CMS

This paper explores the power effects of, and possible justifications for, the differential 'voice' and 'silence' accorded to academic and non-academic subjects within Critical Management Studies (CMS). I explore these issues through a discussion of the practice of 'giving voice' to some subjects critiqued in CMS journal articles by providing them with the opportunity to publish a 'response'. I question the justification for extending this right only to academic subjects, and use this example to provoke CMS to question further its institutional orientation to issues of voice and silence in relation to the non-academic research subject.

Individual differences in inhibitory control - relationship between baseline activation in lateral PFC and an electrophysiological index of response inhibition

The capacity to inhibit inappropriate responses is crucial for goal-directed behavior. Inhibiting such responses seems to come more easily to some of us than others, however. From where do these individual differences originate? Here, we measured 263 participants' neural baseline activation using resting electroencephalogram. Then, we used this stable neural marker to predict a reliable electrophysiological index of response inhibition capacity in the cued Continuous Performance Test, the NoGo-Anteriorization (NGA). Using a source-localization technique, we found that resting delta, theta, and alpha1 activity in the left middle frontal gyrus and resting alpha1 activity in the right inferior frontal gyrus were negatively correlated with the NGA. As a larger NGA is thought to represent better response inhibition capacity, our findings demonstrate that lower levels of resting slow-wave oscillations in the lateral prefrontal cortex, bilaterally, are associated with a better response inhibition capacity.

Applying integrated resource and environmental management to transmission right-of-way maintenance

The concept of a substantive integrator is introduced as a method for integrated resource and environmental management as a means to assimilate different resource values at the operational or field level. A substantive integrator is a strategic management tool for integrating multiple uses into coprorate management regimes that traditionally manage for single values. Wildlife habitat management is presented as a substantive integrator for managing vegetation on electric utility power line corridors. A case study from northern British Columbia provides an example of wildlife habitat management as a means to integrate other resource values such as aesthetics, access and subsistence along British Columbia Hydro and Power Authority's transmission rights-of-way.

Cranes, claims and a statutory right of user

In larger developments there is potential for construction cranes to encroach into the airspace of neighbouring properties. To resolve issues of this nature, a statutory right of user may be sought under s 180 of the Property Law Act 1974 (Qld). Section 180 allows the court to impose a statutory right of user on servient land where it is reasonably necessary in the interests of effective use in any reasonable manner of the dominant land. Such an order will not be made unless the court is satisfied that it is consistent with public interest, the owner of the servient land can be adequately recompensed for any loss or disadvantage which may be suffered from the imposition and the owner of the servient land has refused unreasonably to agree to accept the imposition of that obligation. In applying the statutory provision, a key practical concern for legal advisers will be the basis for assessment of compensation. A recent decision of the Queensland Supreme Court (Douglas J) provides guidance concerning matters relevant to this assessment. The decision is Lang Parade Pty Ltd v Peluso [2005] QSC 112.

Statutory right of user imposed for landlocked land

The decision of McMurdo J in Pacific Coast Investments Pty Ltd v Cowlishaw [2005] QSC 259 concerned an application under s 180 of the Property Law Act 1974 (Qld) for a statutory right of user.

Stop whining and make the best of it: a cross-national comparison of response to regional disadvantage in the wine industry

Our cross-national field study of wine entrepreneurship in the “wrong” places provides some redress to the focus of the “regional advantage” literature on places that have already won and on the firms that benefit from “clusters” and other centers of industry advantage. Regional “disadvantage” is at best a shadowy afterthought to this literature. By poking around in these shadows, we help to synthesize and extend the incipient yet burgeoning literature on entrepreneurial “resourcefulness” and we contribute to the developing body of insights and theory pertinent to the numerous but often ignored firms and startups that mostly need to worry about how they will compete at all now if they are ever to have of chance of “winning” in the future. The core of our findings suggests that understandable – though contested – processes of ingenuity underlie entrepreneurial responses to regional disadvantage. Because we study entrepreneurship that from many angles simply does not make sense, we are also able to proffer a novel perspective on entrepreneurial sensemaking.

The divine right of ...judges

Poem published in Free Speech segment of NTEU Newletter.

Statutory right of user - its impact in practice?

Scenario 1 A buys a two storey commercial building built along the only street frontage to the property. Vehicles cannot reach the rear of the property as the building extends across the entire width of the land. A bought the building with full knowledge that vehicular access to the rest of the property had been compromised by a desire to obtain maximum street frontage for the building which was occupied by a commercial tenant. On street parking is scarce in the surrounding area. A (to the knowledge of the adjoining owner B) constructs a carpark at the rear of the building. The employees of A’s tenant have been using the carpark obtaining access via a driveway on B’s land. To formalise this arrangement, A seeks a right of way for vehicles to travel down B’s driveway to access the carpark...

Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

The ability to inhibit unwanted actions is a heritable executive function that may confer risk to disorders such as attention deficit hyperactivity disorder (ADHD). Converging evidence from pharmacology and cognitive neuroscience suggests that response inhibition is instantiated within frontostriatal circuits of the brain with patterns of activity that are modulated by the catecholamines dopamine and noradrenaline. A total of 405 healthy adult participants performed the stop-signal task, a paradigmatic measure of response inhibition that yields an index of the latency of inhibition, termed the stop-signal reaction time (SSRT). Using this phenotype, we tested for genetic association, performing high-density single-nucleotide polymorphism mapping across the full range of autosomal catecholamine genes. Fifty participants also underwent functional magnetic resonance imaging to establish the impact of associated alleles on brain and behaviour. Allelic variation in polymorphisms of the dopamine transporter gene (SLC6A3: rs37020; rs460000) predicted individual differences in SSRT, after corrections for multiple comparisons. Furthermore, activity in frontal regions (anterior frontal, superior frontal and superior medial gyri) and caudate varied additively with the T-allele of rs37020. The influence of genetic variation in SLC6A3 on the development of frontostriatal inhibition networks may represent a key risk mechanism for disorders of behavioural inhibition.

Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults

CONTEXT AND OBJECTIVE: Suboptimal vitamin D status can be corrected by vitamin D supplementation, but individual responses to supplementation vary. We aimed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D (25(OH)D) after supplementation. DESIGN AND PARTICIPANTS: We used data from a pilot randomized controlled trial in which 644 adults aged 60 to 84 years were randomly assigned to monthly doses of placebo, 30 000 IU, or 60 000 IU vitamin D3 for 12 months. Baseline characteristics were obtained from a self-administered questionnaire. Eighty-eight single-nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray technology. Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay. We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels. RESULTS: Supplement dose and baseline 25(OH)D level explained 24% of the variability in response to supplementation. Body mass index, self-reported health status, and ambient UV radiation made a small additional contribution. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6, and HERC2 were associated with change in 25(OH)D level, although only CYP2R1 was significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors. CONCLUSION: Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation, perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of 25(OH)D.

Compensation or consideration for a statutory right of user?

Section 180 of the Property Law Act 1974 (Qld) makes provision for an applicant to seek a statutory right of user over a neighbour’s property where such right of use is reasonably necessary in the interests of effective use in any reasonable manner of the dominant land. A key issue in an application under s 180 is compensation. Unfortunately, while s 180 expressly contemplates that an order for compensation will include provision for payment of compensation to the owner of servient land there are certain issues that are less clear. One of these is the basis for determination of the amount of compensation. In this regard, s 180(4)(a) provides that, in making an order for a statutory right of user, the court: (a) shall, except in special circumstances, include provision for payment by the applicant to such person or persons as may be specified in the order of such amount by way of compensation or consideration as in the circumstances appears to the court to be just The operation of this statutory provision was considered by de Jersey CJ (as he then was) in Peulen v Agius [2015] QSC 137.

A right of resale? Indigenous art under the hammer

This week, Sotheby's sold the late Clifford Possum Tjapaltjarri's painting, Warlugulong. The auction-house's spokesman, Tim Klingender, was enthusiastic about the high price commanded by the art work: "The painting was a really great painting and it deserved to make a really fantastic price, and it made that price."

Finite element analysis investigation of response of pumpkin tissue under uniaxial loading

Finite element analysis (FEA) models of uniaxial loading of pumpkin peel and flesh tissues were developed and validated using experimental results. The tensile model was developed for both linear elastic and plastic material models, the compression model was develop d only with the plastic material model. The outcomes of force versus time curves obtained from FEA models followed similar pattern to the experimental curves however the curve resulted with linear elastic material properties had a higher difference with the experimental curves. The values of predicted forces were determined and compared with the experimental curve. An error indicator was introduced and computed for each case and compared. Additionally Root Mean Square Error (RMSE) values were also calculated for each model and compared. The results of modelling were used to develop material model for peel and flesh tissues in FEA modelling of mechanical peeling of tough skinned vegetables.