Striking a balance: Resolving conflicts between the duty of confidentiality and duties to third parties in genetics

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.Genetic information is relevant not only to the patient, but also to their family. Where a patient refuses to share that information with family members, then their legal rights may conflict. This paper focuses on that conflict between the rights of individuals and the rights of third parties. We first examine the nature of the duty of confidence as it applies in these circumstances, and the extent to which it can appropriately accommodate the familial nature of genetic information. We then consider the situations in which a health care practitioner might owe a third party family member a tortious duty of care. We conclude that in most cases, there will be no duty owed to third parties, but that in certain limited circumstances, a duty of care should arise.The authors are grateful to Professor Anneke Lucassen, Dr Daniele Carrier, Dr Sandi Dheensa and the Recontacting in Mainstreaming Genetics project team, Professor Andrea Lista, Professor Charlotte Waelde, Professor Christian Witting, Dr Paula Boddington and members of the Science, Culture and the Law research group at the University of Exeter Law School for comments on earlier drafts of this paper. Naomi Hawkins is supported by the ESRC (grant codes ES/K009575/1 and ES/L002868/1)

Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycolaldehyde-modified low-density lipoproteins

Aims/hypothesis: Previous studies have shown that glycation of LDL by methylglyoxal and glycolaldehyde, in the absence of significant oxidation, results in lipid accumulation in macrophage cells. Such 'foam cells' are a hallmark of atherosclerosis. In this study we examined whether LDL glycation by methylglyoxal or glycolaldehyde, and subsequent lipid loading of cells, can be inhibited by agents that scavenge reactive carbonyls. Such compounds may have therapeutic potential in diabetes-associated atherosclerosis. Materials and methods: LDL was glycated with methylglyoxal or glycolaldehyde in the absence or presence of metformin, aminoguanidine, Girard's reagents P and T, or hydralazine. LDL modification was characterised by changes in mobility (agarose gel electrophoresis), cross-linking (SDS-PAGE) and loss of amino acid residues (HPLC). Accumulation of cholesterol and cholesteryl esters in murine macrophages was assessed by HPLC. Results: Inhibition of LDL glycation was detected with equimolar or greater concentrations of the scavengers over the reactive carbonyl. This inhibition was structure-dependent and accompanied by a modulation of cholesterol and cholesteryl ester accumulation. With aminoguanidine, Girard's reagent P and hydralazine, cellular sterol levels returned to control levels despite incomplete inhibition of LDL modification. Conclusions/ interpretation: Inhibition of LDL glycation by interception of the reactive aldehydes that induce LDL modification prevents lipid loading and model foam cell formation in murine macrophage cells. Carbonyl-scavenging reagents, such as hydrazines, may therefore help inhibit LDL glycation in vivo and prevent diabetes-induced atherosclerosis. © Springer-Verlag 2006

An Australian longitudinal pilot study examining health determinants of cardiac outcomes 12 months post percutaneous coronary intervention

Background Percutaneous coronary intervention (PCI) is a very common revascularisation procedure for coronary artery disease (CAD). The purpose of this study was to evaluate cardiac outcomes, health related quality of life (HRQoL), resilience and adherence behaviours in patients who have undergone a PCI at two time points (6 and 12 months) following their procedure. Methods A longitudinal pilot study was conducted to observe the cardiac outcomes across a cohort of patients who had undergone a percutaneous coronary intervention (PCI). Participants who had undergone PCI 6 months prior were invited. Those participants who met the inclusion criteria and provided consent then completed a telephone survey (time point 1). These participants were then contacted 6 months later (i.e. 12 months post-intervention, time point 2) and the measures were repeated. Results All patients (n = 51) were recorded as being alive at time point 1. The multiple model indicated that controlling for other factors, gender was significantly associated with a linear combination of outcome measures (p = 0.004). The effect was moderate in magnitude (partial-η2 = 0.303), where males performed significantly better than females 6 months after the PCI procedure physically and with mood. Follow-up univariate ANOVAs indicated that gender differences were grounded in the scale measuring depression (PHQ9) (p = 0.005) and the physical component score of the short form measuring HRQoL (SF12-PCS) (p = 0.003). Thirteen patients were lost to follow-up between time points 1 and 2. One patient was confirmed to have passed away. The pattern of correlations between outcome measures at time point 2 revealed statistically significant negative correlation between the PHQ instrument and the resilience scale (CD-RISC) (r = -0.611; p < 0.001); and the physical component score of the SF-12 instrument (r = -0.437; p = 0.054). Conclusions Men were performing better than women in the 6 months post-PCI, particularly in the areas of mood (depression) and physical health. This pilot results indicate gender-sensitive practices are recommended particularly up to 6 months post-PCI. Any gender differences observed at 6 month appear to disappear at 12 months post-PCI. Further research into the management of mood particularly for women post-PCI is warranted. A more detailed inquiry related to access/attendance to secondary prevention is also warranted

A review of assessment methods for river hydromorphology

The work leading to this paper has received funding for the EU’s FP7 under Grant Agreement No. 282656 (REFORM

The epiphyseal scar: changing perceptions in relation to skeletal age estimation.

BACKGROUND: It is imperative that all methods applied in skeletal age estimation and the criteria on which they are based have a strong evidential basis. The relationship between the persistence of epiphyseal scars and chronological age, however, has remained largely untested. AIMS: To assess the relationships between the level of persistence of the epiphyseal scar and chronological age, biological sex and side of the body in relation to the interpretation of epiphyseal scars in methods of skeletal age estimation. SUBJECTS AND METHODS: A sample of radiographic images was obtained from the Tayside NHS Trust, Ninewells Hospital, Dundee, UK. This included images of four anatomical regions from living female and male individuals aged between 20-50 years. RESULTS: Some remnant of an epiphyseal scar was found in 78-99% of individuals examined in this study. The level of persistence of epiphyseal scars was also found to vary between anatomical regions. CONCLUSION: The overall relationship between chronological age and the level of persistence or obliteration of the epiphyseal scar was found to be of insufficient strength to support a causative link. It is, therefore, necessary that caution is employed in their interpretation in relation to skeletal age estimation practices

The AGNIFS survey: spatially resolved observations of hot molecular and ionized outflows in nearby active galaxies

\ua9 2023 The Author(s). We present the hot molecular and warm ionized gas kinematics for 33 nearby (0.001 ≲ z ≲ 0.056) X-ray selected active galaxies using the H2 2.1218 μm and Br γ emission lines observed in the K band with the Gemini near-infrared integral field spectrograph. The observations cover the inner 0.04–2 kpc of each active galactic nucleus at spatial resolutions of 4–250 pc with a velocity resolution of σinst ≈ 20 km s-1. We find that 31 objects (94 per cent) present a kinematically disturbed region (KDR) seen in ionized gas, while such regions are observed in hot molecular gas for 25 galaxies (76 per cent). We interpret the KDR as being due to outflows with masses of 102–107 and 100–104 M☉ for the ionized and hot molecular gas, respectively. The ranges of mass-outflow rates (M\ub7out) and kinetic power (ĖK) of the outflows are 10-3–101 M☉ yr-1 and ∼1037–1043 erg s-1 for the ionized gas outflows, and 10-5–10-2 M☉ yr-1 and 1035–1039 erg s-1 for the hot molecular gas outflows. The median coupling efficiency in our sample is ĖK/Lbol ≈ 1.8 7 10-3 and the estimated momentum fluxes of the outflows suggest they are produced by radiation-pressure in low-density environment, with possible contribution from shocks

Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

Endocrine therapy and related issues in hormone receptor-positive early breast cancer: a roundtable discussion by the breast cancer therapy expert group (BCTEG)

Purpose: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient’s comorbid conditions, actual versus perceived benefit of treatments, patient’s compliance as well as financial/reimbursement issues, and long-term tolerability of therapy. Methods: A meeting of global oncology experts was convened in January 2017 with the belief that there is a gap in clinical practice guidance on several fundamental issues in breast cancer care, particularly in the community setting, where oncologists may encounter multiple tumor types. The goal was to discuss some of the most important questions in this area and provide some guidance for practicing oncologists. Results: Topics addressed included risk of contralateral breast cancer recurrence in patients with estrogen receptor-positive early breast cancer who have undergone 5 years of adjuvant endocrine therapy, adverse events associated with endocrine therapy and their management, emergent data on adjuvant bisphosphonate therapy and its apparent benefit in reducing breast cancer recurrence, recent findings of extended adjuvant endocrine therapy trials, and the use of currently available genomic biomarker tests as a means of further informing treatment decisions. Conclusions: A summary of the discussion on these topics and several ‘expert opinion statements’ are provided herein in an effort to convey the collective insights of the panel as it relates to current standard practice

The development of novel LTA4H modulators to selectively target LTB4 generation

The pro-inflammatory mediator leukotriene B4 (LTB4) is implicated in the pathologies of an array of diseases and thus represents an attractive therapeutic target. The enzyme leukotriene A4 hydrolase (LTA4H) catalyses the distal step in LTB4 synthesis and hence inhibitors of this enzyme have been actively pursued. Despite potent LTA4H inhibitors entering clinical trials all have failed to show efficacy. We recently identified a secondary anti-inflammatory role for LTA4H in degrading the neutrophil chemoattractant Pro-Gly-Pro (PGP) and rationalized that the failure of conventional LTA4H inhibitors may be that they inadvertently prevented PGP degradation. We demonstrate that these inhibitors do indeed fail to discriminate between the dual activities of LTA4H, and enable PGP accumulation in mice. Accordingly, we have developed novel compounds that potently inhibit LTB4 generation whilst leaving PGP degradation unperturbed. These novel compounds could represent a safer and superior class of LTA4H inhibitors for translation into the clinic

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue