Editorial: The Human Fertilisation and Embryology Act 2008

This editorial first describes the workshop out of which the present special issue arose. The editors then identify the need for a multidisciplinary collection examining the Human Fertilisation and Embryology Act 2008 from both legal and political perspectives, including the consultation process, campaigning and parliamentary debates leading to its passage, and the concluded legislation and its effects. The editorial provides an overview of the legislative reform process, key legislative changes, and the various contributions to the special issue. Cross-cutting themes include the value of a qualitative, discourse-based approach to research in this area; the need to understand the 2008 Act in historical context; unforeseen practical implications of the legislative provisions; and silences and missed opportunities in the legislation. Finally, a postscript covers the changing landscape of hybrid embryo research since the passage of the Act, and the uncertain future of the Human Fertilisation and Embryology Authority at the time of writing.

Determination of vertical hydraulic conductivity of aquitards in a multilayered leaky system using water-level signals in adjacent aquifers

This paper presents a methodology for determining the vertical hydraulic conductivity (Kv) of an aquitard, in a multilayered leaky system, based on the harmonic analysis of arbitrary water-level fluctuations in aquifers. As a result, Kv of the aquitard is expressed as a function of the phase-shift of water-level signals measured in the two adjacent aquifers. Based on this expression, we propose a robust method to calculate Kv by employing linear regression analysis of logarithm transformed frequencies and phases. The frequencies, where the Kv are calculated, are identified by coherence analysis. The proposed methods are validated by a synthetic case study and are then applied to the Westbourne and Birkhead aquitards, which form part of a five-layered leaky system in the Eromanga Basin, Australia.

The difficulty of establishing causation in medical negligence cases : two recent Australian decisions

This editorial on health and guardianship law provides an overview of the causation issues that precluded the recovery of two medical negligence claims in the cases of Wallace v Kam [2013] HCA 19 and Waller v James [2013] NSWSC 497.

Double standards in special medical research : questioning the discrepancy between requirements for medical research involving incompetent adults and medical research involving children

Medical research represents a substantial departure from conventional medical care. Medical care is patient-orientated, with decisions based on the best interests and/or wishes of the person receiving the care. In contrast, medical research is future-directed. Primarily it aims to contribute new knowledge about illness or disease, or new knowledge about interventions, such as drugs, that impact upon some human condition. Current State and Territory laws and research ethics guidelines in Australia relating to the review of medical research appropriately acknowledge that the functions of medical care and medical research differ. Prior to a medical research project commencing, the study must be reviewed and approved by a Human Research Ethics Committee (HREC). For medical research involving incompetent adults, some jurisdictions require an additional, independent safeguard by way of tribunal or court approval of medical research protocols. This extra review process reflects the uncertainty of medical research involvement, and the difficulties surrogate decision-makers of incompetent adults face in making decisions about others, and deliberating about the risks and benefits of research involvement. Parents of children also face the same difficulties when making decisions about their child’s research involvement. However, unlike the position concerning incompetent adults, there are no similar safeguards under Australian law in relation to the approval of medical research involving children. This column questions why this discrepancy exists with a view to generating further dialogue on the topic.

Alcohol-related violence presenting to the emergency department : is ‘glassing’ the big issue?

Objective Describe the characteristics of patients presenting to Emergency Departments (EDs) within Queensland, Australia with injuries due to assault with a glass implement (‘glassing’) and to set this within the broader context of presentations due to alcohol-related violence. Methods Analysis of prospectively collected ED injury surveillance data collated by the Queensland Injury Surveillance Unit (QISU) between 1999 and 2011. Cases of injury due to alcohol-related violence were identified and analysed using coded fields supplemented with qualitative data contained within the injury description text. Descriptive statistics were used to assess the characteristics of injury presentations due to alcohol-related violence. Violence included interpersonal violence and aggression (verbal aggression and object violence). Results A total of 4629 cases were studied. The study population was predominantly male (72%) and aged 18 to 24 (36%), with males in this age group comprising more than a quarter of the study population (28%). Nine percent of alcohol-related assault injuries were a consequence of ‘glassing’. The home was the most common location for alcohol-related violence (31%) and alcohol-related ‘glassings’ (33%). Overall, the most common glass object involved was a bottle (75%), however, within licensed venues an even mix of a drinking glass (44%) and glass bottle (45%) were identified. Conclusions Contrary to public perception generated by media, ‘glassing’ incidents, particularly at licensed venues, constitute a relatively small proportion of all alcohol-related violence. The current study highlights the predominance of young men injured following alcohol-related violence, demonstrating a key focus area within the population for aiming prevention strategies.

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

TLR2, but Not TLR4, is required for effective host defence against Chlamydia respiratory tract infection in early life

Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.

Chlamydia muridarum lung infection in infants alters hematopoietic cells to promote allergic airway disease in mice

Background Viral and bacterial respiratory tract infections in early-life are linked to the development of allergic airway inflammation and asthma. However, the mechanisms involved are not well understood. We have previously shown that neonatal and infant, but not adult, chlamydial lung infections in mice permanently alter inflammatory phenotype and physiology to increase the severity of allergic airway disease by increasing lung interleukin (IL)-13 expression, mucus hyper-secretion and airway hyper-responsiveness. This occurred through different mechanisms with infection at different ages. Neonatal infection suppressed inflammatory responses but enhanced systemic dendritic cell:T-cell IL-13 release and induced permanent alterations in lung structure (i.e., increased the size of alveoli). Infant infection enhanced inflammatory responses but had no effect on lung structure. Here we investigated the role of hematopoietic cells in these processes using bone marrow chimera studies. Methodology/Principal Findings Neonatal (<24-hours-old), infant (3-weeks-old) and adult (6-weeks-old) mice were infected with C. muridarum. Nine weeks after infection bone marrow was collected and transferred into recipient age-matched irradiated naïve mice. Allergic airway disease was induced (8 weeks after adoptive transfer) by sensitization and challenge with ovalbumin. Reconstitution of irradiated naïve mice with bone marrow from mice infected as neonates resulted in the suppression of the hallmark features of allergic airway disease including mucus hyper-secretion and airway hyper-responsiveness, which was associated with decreased IL-13 levels in the lung. In stark contrast, reconstitution with bone marrow from mice infected as infants increased the severity of allergic airway disease by increasing T helper type-2 cell cytokine release (IL-5 and IL-13), mucus hyper-secretion, airway hyper-responsiveness and IL-13 levels in the lung. Reconstitution with bone marrow from infected adult mice had no effects. Conclusions These results suggest that an infant chlamydial lung infection results in long lasting alterations in hematopoietic cells that increases the severity of allergic airway disease in later-life.

Relationship between CEO salaries and performance of banks in Australia and Germany

Purpose: The purpose of this paper was to examine the relationship between CEO salaries and firm performance in the banking sector. Design/methodology/approach: The data relating to a six year period (2007 - 2012) was gathered from databases and the websites of the major banks in Australia and Germany. The data was subjected to Regression and Pearson Correlation Analysis to test if there was a positive correlation between total salary including incentive bonuses against the variables indicating the performance of the firm. Findings: The tests indicate a weak relationship between the CEO salary package and the key indicators of a firm's performance in Australian banks but a strong relationship in the German banks. Research limitations/implications: This study was limited in that it only covers the major banks in Australia and Germany and may therefore not be relevant to different countries with different economic climates. Practical implications: This study provides additional evidence to support the continued debate regarding the need to have greater accountability for CEO salary packages linked to actual performance measures of firms. Originality/value: This paper adds to the literature in so far as it compares two different Countries of the banking sector in a global market

Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non-small-cell lung cancer

Purpose: In non-small-cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play major roles in tumorigenesis. This phase I/II study evaluated combined therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib and the COX-2 inhibitor rofecoxib in platinum-pretreated, relapsed, metastatic NSCLC (n = 45). Patients and Methods: Gefitinib 250 mg/d was combined with rofecoxib (dose escalated from 12.5 to 25 to 50 mg/d through three cohorts, each n = 6). Because the rofecoxib maximum-tolerated dose was not reached, the 50 mg/d cohort was expanded for efficacy evaluation (n = 33). Results: Among the 42 assessable patients, there was one complete response (CR) and two partial responses (PRs) and 12 patients with stable disease (SD); disease control rate was 35.7% (95% CI, 21.6% to 52.0%). Median time to tumor progression was 55 days (95% CI, 47 to 70 days), and median survival was 144 days (95% CI, 103 to 190 days). In a pilot study, matrix-assisted laser desorption/ionization (MALDI) proteomics analysis of baseline serum samples could distinguish patients with an objective response from those with SD or progressive disease (PD), and those with disease control (CR, PR, and SD) from those with PD. The regimen was generally well tolerated, with predictable toxicities including skin rash and diarrhea. Conclusion: Gefitinib combined with rofecoxib provided disease control equivalent to that expected with single-agent gefitinib and was generally well tolerated. Baseline serum proteomics may help identify those patients most likely to benefit from EGFR TKIs. © 2007 by American Society of Clinical Oncology.

Food availability, cost disparity and improvement in relation to accessibility and remoteness in Queensland

This study is the first to describe disparity and change in the food supply between metropolitan, rural and remote stores by Accessibility/Remoteness Index of Australia (ARIA)1 category. A total of 92 stores (97% response rate) within five aggregate ARIA categories participated throughout Queensland in 2000. There was a strong association between ARIA category and the cost of the basket of basic foods, with prices being significantly higher (20% and 31% respectively) in the ‘remote’ and ‘very remote’ categories than in the ‘highly accessible’ category. The association with ARIA was less marked for fruit and vegetables than for other food groups, but not for tobacco and take-away food items. Basic food items were less available in the more remote stores. Over the past two years, relative improvements in food prices have been seen in stores in the ‘very remote’ category, with observed increases less than the consumer price index (CPI) for food. Some factors which may have contributed to this improvement are discussed.

Health and guardianship law : the decision of X v the Sydney Children's Hospitals Network [2013] NSWCA 320 : mature minors and the refusal of blood products

This recent decision of the New South Wales Court of Appeal considers the scope of the parens patriae jurisdiction in cases where the jurisdiction is invoked for the protection of a Gillick competent minor. As outlined below, in certain circumstances the law recognises that mature minors are able to make their own decisions concerning medical treatment. However, there have been a number of Commonwealth decisions which have addressed the issue of whether mature minors are able to refuse medical procedures in circumstances where refusal will result in the minor dying. Ultimately, this case confirms that the minor does not necessarily have a right to make autonomous decisions; the minor’s right to exercise his or her autonomous decision only exists when such decision accords with what is deemed to be in his or her best interests.

Vascular remodeling in the internal mammary artery graft and association with in situ endothelin-1 and receptor expression

BACKGROUND: The vasoconstricting peptide endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, vascular smooth muscle cell (VSMC) growth stimulation, and intimal thickening. ET-1 binds 2 receptor subtypes, endothelin A and B, and the ETA receptor mediates vasoconstriction and VSMC growth. This study aims to quantitatively assess arterial remodeling variables and compare them with changes in ET-1, ETA, and ETB expression in the internal mammary artery (IMA). METHODS AND RESULTS: Specimens from 55 coronary artery disease (CAD) patients (45 men, 10 women; mean age 65 years) and 14 control IMA specimens (from 7 men and 7 women; mean age 45 years) were collected. IMA cross sections were assessed by histochemical and immunohistochemical staining methods to quantify the levels of medionecrosis, fibrosis, VSMC growth, ET-1, ETA, ETB, and macrophage infiltration. The percentage area of medionecrosis in the patients was almost double that in the controls (31.85+/-14.52% versus 17.10+/-9.96%, P=0.0006). Total and type 1 collagen was significantly increased compared with controls (65.8+/-18.3% versus 33.7+/-13.7%, P=0.07, and 14.2+/-10.0% versus 4.8+/-2.8%, P=0.01, respectively). Despite ACE and/or statin therapy, ET-1 expression and cell cycling were significantly elevated in the patient IMAs relative to the controls (46.27+/-18.46 versus 8.56+/-8.42, P=0.0001, and 37.29+/-12.88 versus 11.06+/-8.18, P=0.0001, respectively). ETA and ETB staining was elevated in the patient vessels (46.88+/-11.52% versus 18.58+/-7.65%, P=0.0001, and 42.98+/-7.08% versus 34.73+/-5.20%, P=0.0067, respectively). A mild presence of macrophages was noted in all sections. CONCLUSIONS: Elevated distribution of collagen indicative of fibrosis coupled with increased cell cycling and high levels of ET-1 and ETA expression in the absence of chronic inflammation suggests altered IMA VSMC regulation is fundamental to the remodeling process.

'Explain in plain English' questions revisited : data structures problems

Recent studies have linked the ability of novice (CS1) programmers to read and explain code with their ability to write code. This study extends earlier work by asking CS2 students to explain object-oriented data structures problems that involve recursion. Results show a strong correlation between ability to explain code at an abstract level and performance on code writing and code reading test problems for these object-oriented data structures problems. The authors postulate that there is a common set of skills concerned with reasoning about programs that explains the correlation between writing code and explaining code. The authors suggest that an overly exclusive emphasis on code writing may be detrimental to learning to program. Non-code writing learning activities (e.g., reading and explaining code) are likely to improve student ability to reason about code and, by extension, improve student ability to write code. A judicious mix of code-writing and code-reading activities is recommended.