Guiding principles for evaluating the impacts of conservation interventions on human well-being

Measures of socio-economic impacts of conservation interventions have largely been restricted to externally defined indicators focused on income, which do not reflect people's priorities. Using a holistic, locally grounded conceptualization of human well-being instead provides a way to understand the multi-faceted impacts of conservation on aspects of people's lives that they value. Conservationists are engaging with well-being for both pragmatic and ethical reasons, yet current guidance on how to operationalize the concept is limited. We present nine guiding principles based around a well-being framework incorporating material, relational and subjective components, and focused on gaining knowledge needed for decision-making. The principles relate to four key components of an impact evaluation: (i) defining well-being indicators, giving primacy to the perceptions of those most impacted by interventions through qualitative research, and considering subjective well-being, which can affect engagement with conservation; (ii) attributing impacts to interventions through quasi-experimental designs, or alternative methods such as theory-based, case study and participatory approaches, depending on the setting and evidence required; (iii) understanding the processes of change including evidence of causal linkages, and consideration of trajectories of change and institutional processes; and (iv) data collection with methods selected and applied with sensitivity to research context, consideration of heterogeneity of impacts along relevant societal divisions, and conducted by evaluators with local expertise and independence from the intervention

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI

Prostate tumor attenuation in the nu/nu murine model due to anti-sarcosine antibodies in folate-targeted liposomes

Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa

Informed consent in veterinary medicine: ethical implications for the profession and the animal 'patient'

Informed consent processes are a vital component of both human and veterinary medicine. Current practice encourages veterinarians to learn from insights in the human medical field about how best to achieve valid consent. However, drawing on published literature in veterinary and medical ethics, this paper identifies considerable differences between the purposes of veterinary and human medical consent. Crucially, it is argued that the legal status of animal patients as ‘property’ has implications for the ethical role of veterinary informed consent and the protection of the animal ‘patient’. It is suggested that veterinary informed consent should be viewed as an ethical pivot point where the multiple responsibilities of a veterinary professional converge. In practice, balancing these responsibilities creates considerable ethical challenges. As an example, the paper discusses the renewed call for UK veterinarians to make animal welfare their first priority; we predict that this imperative may increasingly cause veterinary informed consent to become an ethical pressure point due to tensions caused by the often conflicting interests of animals, owners and the veterinary profession. In conclusion, the paper argues that whilst gaining informed consent can often be presented as a robust ethical justification in human medicine, the same cannot be said in veterinary medicine. If the veterinary profession wish to prioritise animal welfare, there is an urgent need to re-evaluate the nature of authority gained through owner informed consent and to consider whether animal patients might need to be better protected outside the consent process in certain circumstances

Resource profile and user guide of the Polygenic Index Repository

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies — some not previously published — from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available

Intensive medical student involvement in short-term surgical trips provides safe and effective patient care: a case review

<p>Abstract</p> <p>Background</p> <p>The hierarchical nature of medical education has been thought necessary for the safe care of patients. In this setting, medical students in particular have limited opportunities for experiential learning. We report on a student-faculty collaboration that has successfully operated an annual, short-term surgical intervention in Haiti for the last three years. Medical students were responsible for logistics and were overseen by faculty members for patient care. Substantial planning with local partners ensured that trip activities supplemented existing surgical services. A case review was performed hypothesizing that such trips could provide effective surgical care while also providing a suitable educational experience.</p> <p>Findings</p> <p>Over three week-long trips, 64 cases were performed without any reported complications, and no immediate perioperative morbidity or mortality. A plurality of cases were complex urological procedures that required surgical skills that were locally unavailable (43%). Surgical productivity was twice that of comparable peer institutions in the region. Student roles in patient care were greatly expanded in comparison to those at U.S. academic medical centers and appropriate supervision was maintained.</p> <p>Discussion</p> <p>This demonstration project suggests that a properly designed surgical trip model can effectively balance the surgical needs of the community with an opportunity to expose young trainees to a clinical and cross-cultural experience rarely provided at this early stage of medical education. Few formalized programs currently exist although the experience above suggests the rewarding potential for broad-based adoption.</p

Ethics, economics and the regulation and adoption of new medical devices: case studies in pelvic floor surgery

<p>Abstract</p> <p>Background</p> <p>Concern has been growing in the academic literature and popular media about the licensing, introduction and adoption of surgical devices before full effectiveness and safety evidence is available to inform clinical practice. Our research will seek empirical survey evidence about the roles, responsibilities, and information and policy needs of the key stakeholders in the introduction into clinical practice of new surgical devices for pelvic floor surgery, in terms of the underlying ethical principals involved in the economic decision-making process, using the example of pelvic floor procedures.</p> <p>Methods/Design</p> <p>Our study involves three linked case studies using, as examples, selected pelvic floor surgery devices representing Health Canada device safety risk classes: low, medium and high risk. Data collection will focus on stakeholder roles and responsibilities, information and policy needs, and perceptions of those of other key stakeholders, in seeking and using evidence about new surgical devices when licensing and adopting them into practice. For each class of device, interviews will be used to seek the opinions of stakeholders. The following stakeholders and ethical and economic principles provide the theoretical framework for the study:</p> <p indent="1"><b>Stakeholders </b>- federal regulatory body, device manufacturers, clinicians, patients, health care institutions, provincial health departments, and professional societies. Clinical settings in two centres (in different provinces) will be included.</p> <p indent="1"><b>Ethics </b>- beneficence, non-maleficence, autonomy, justice.</p> <p indent="1"><b>Economics </b>- scarcity of resources, choices, opportunity costs.</p> <p>For each class of device, responses will be analysed to compare and contrast between stakeholders. Applied ethics and economic theory, analysis and critical interpretation will be used to further illuminate the case study material.</p> <p>Discussion</p> <p>The significance of our research in this new area of ethics will lie in providing recommendations for regulatory bodies, device manufacturers, clinicians, health care institutions, policy makers and professional societies, to ensure surgical patients receive sufficient information before providing consent for pelvic floor surgery. In addition, we shall provide a wealth of information for future study in other areas of surgery and clinical management, and provide suggestions for changes to health policy.</p

Stress-Induced C/EBP Homology Protein (CHOP) Represses MyoD Transcription to Delay Myoblast Differentiation

When mouse myoblasts or satellite cells differentiate in culture, the expression of myogenic regulatory factor, MyoD, is downregulated in a subset of cells that do not differentiate. The mechanism involved in the repression of MyoD expression remains largely unknown. Here we report that a stress-response pathway repressing MyoD transcription is transiently activated in mouse-derived C2C12 myoblasts growing under differentiation-promoting conditions. We show that phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α) is followed by expression of C/EBP homology protein (CHOP) in some myoblasts. ShRNA-driven knockdown of CHOP expression caused earlier and more robust differentiation, whereas its constitutive expression delayed differentiation relative to wild type myoblasts. Cells expressing CHOP did not express the myogenic regulatory factors MyoD and myogenin. These results indicated that CHOP directly repressed the transcription of the MyoD gene. In support of this view, CHOP associated with upstream regulatory region of the MyoD gene and its activity reduced histone acetylation at the enhancer region of MyoD. CHOP interacted with histone deacetylase 1 (HDAC1) in cells. This protein complex may reduce histone acetylation when bound to MyoD regulatory regions. Overall, our results suggest that the activation of a stress pathway in myoblasts transiently downregulate the myogenic program

Non invasive prenatal testing for single gene disorders:Exploring the ethics

Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for ‘information only', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care