Mass spectrometry of polymers: A tutorial review.

Ever since the inception of synthetic polymeric materials in the late 19th century, the number of studies on polymers as well as the complexity of their structures have only increased. The development and commercialization of new polymers with properties fine-tuned for specific technological, environmental, consumer, or biomedical applications requires powerful analytical techniques that permit the in-depth characterization of these materials. One such method with the ability to provide chemical composition and structure information with high sensitivity, selectivity, specificity, and speed is mass spectrometry (MS). This tutorial review presents and exemplifies the various MS techniques available for the elucidation of specific structural features in a synthetic polymer, including compositional complexity, primary structure, architecture, topology, and surface properties. Key to every MS analysis is sample conversion to gas-phase ions. This review describes the fundamentals of the most suitable ionization methods for synthetic materials and provides relevant sample preparation protocols. Most importantly, structural characterizations via one-step as well as hyphenated or multidimensional approaches are introduced and demonstrated with specific applications, including surface sensitive and imaging techniques. The aim of this tutorial review is to illustrate the capabilities of MS for the characterization of large, complex polymers and emphasize its potential as a powerful compositional and structural elucidation tool in polymer chemistry.

Factors Influencing PROMIS Scores and Patient Reported Outcomes Following Surgical Intervention of Isolated Lisfranc Injury: Minimum 2 Year Follow-up.

Lisfranc injuries are rare but significant foot injuries, as they often result from polytrauma patients, and are often misdiagnosed, which further complicate their evaluation and contribute to their propensity towards disability. It is recommended that, on diagnosis, Lisfranc injuries be treated as soon as possible to decrease the risk of future chronic pain, disability, or osteoarthritis. Our study evaluated patients who completed the patient reported outcome measurement information systems (PROMIS) along with the foot function index (FFI) following operative fixation for Lisfranc injury. Fifty-one patients between 2010 and 2020 met inclusion criteria and were selected for this study, with completion. Utilizing the electronic medical record (EMR), patient charts were reviewed to obtain basic patient demographic information and comorbidities. Operative reports were reviewed to determine which procedure was performed for definitive fixation. Primary arthrodesis was associated with a significant decrease in complication rates (p = .025) when compared to ORIF. Females, arthrodesis, and procedures using a home run (HR) screw were independent risk factors for significantly higher reports of PROMIS pain interference. Arthrodesis also was associated with lower PROMIS pain interference scores. Arthrodesis and males exhibited higher scores in all FFI categories. Our results provide evidence that patient reported outcomes following Lisfranc surgery reported via PROMIS, FFI and VAS scores are independently influenced by patient demographics, comorbidities, and surgical variables. Analysis of potential associations between these patient characteristics and PROMIS and FFI scores provides evidence for physicians to manage patient expectations prior to operative treatment of a nonpolytraumatic Lisfranc injury.

A New Defense of Brain Death as the Death of the Human Organism.

This paper provides a new rationale for equating brain death with the death of the human organism, in light of well-known criticisms made by Alan D Shewmon, Franklin Miller and Robert Truog and a number of other writers. We claim that these criticisms can be answered, but only if we accept that we have slightly redefined the concept of death when equating brain death with death simpliciter. Accordingly, much of the paper defends the legitimacy of redefining death against objections, before turning to the specific task of defending a new rationale for equating brain death with death as slightly redefined.

Guiding Genomic Research: Australia's National Statement on Ethical Conduct in Human Research.

With advances in genomic research playing an important role in the development of clinical applications, it is important that ethical guidance for researchers is contemporary and relevant. In this article we analyse the relevant provisions in Australia's National Statement on Ethical Conduct in Human Research (revised in 2018) and consider the guidance it provides for contemporary genomics research. We analyse four key areas: genomic information; biobanking and use of human tissue; consent to participation in genomic research, including specific issues related to participation by children; and return of findings. We conclude that Australia's National Statement is well-placed to provide guidance to Australian researchers on issues relating to genomics, although there is scope for additional guidance on some issues related to consent.

Using the therapy and enhancement distinction in law and policy.

In a first major study, the UK's Royal Society found that 76% of people in the UK are in favour of therapeutic germline genomic editing to correct genetic diseases in human embryos, but found there was little appetite for germline genomic editing for non-therapeutic purposes. Assuming the UK and other governments acted on these findings, can lawmakers and policymakers coherently regulate the use of biomedical innovations by permitting their use for therapeutic purposes but prohibiting their use for enhancement purposes? This paper examines the very common claim in the enhancement literature that the therapy v enhancement distinction does little meaningful work in helping us think through the ethical issues, a claim that has significant implications for these lawmakers and policymakers who may wish to regulate genomic editing techniques to reflect the findings of this important study. The focus of this paper is on germline genomic editing as one of the main themes in this special issue.

Outcomes of knee replacement in patients with posttraumatic arthritis due to previous tibial plateau fracture.

INTRODUCTION: Tibial plateau fractures are routinely treated with open reduction internal fixation (ORIF); however, the long-term results of ORIF are unclear. The purpose of the current study is to evaluate outcomes in these patients, including: the rate of conversion of ORIF to total knee arthroplasty (TKA), the relationship between elevated inflammatory markers after the initial ORIF and subsequent infection in TKA, and the rationale behind performing the conversion to TKA in one step versus two steps. METHODS: Using current procedural terminology (CPT) codes, we assembled a cohort of 891 patients (933 knees) who underwent ORIF for a tibial plateau fracture from 2007 to 2017 at the investigating institution. The patients were then reviewed for pertinent demographic information and for the outcomes of interest. RESULTS: Of the 933 knees, a total of 20 knees (2.15%) required conversion from ORIF to TKA. Of the 20 knees that underwent conversion to TKA, three were performed as a two-stage conversion. Of the 20 knees that underwent TKA, seven experienced postoperative arthrofibrosis, four experienced postoperative infection, and four required revision. CONCLUSION: Our retrospective study suggests that the need for conversion to TKA is uncommon following ORIF of a tibial plateau fracture. Furthermore, the conversion to TKA can be performed as a one- or two-stage procedure, and based on our study, we suggest that there may be higher rates of infection with the single stage conversion. LEVEL OF EVIDENCE: Level III, Retrospective study.

Evaluation of fluorescence-guided surgery agents in a murine model of soft tissue fibrosarcoma.

BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence-guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection-associated morbidity while improving local tumor control. METHODS: We evaluate the tumor-targeting specificity and utility of fluorescence-imaging agents to provide disease-specific contrast. Mice with HT1080 fibrosarcoma tumors received one of five probes: cetuximab-IRDye800CW (anti-EGFR), DC101-IRDye800CW (anti-VEGFR-2), IgG-IRDye800CW, the cathepsin-activated probe Prosense750EX, or the small molecule probe IntegriSense750. Tumors were imaged daily using open- and closed-field fluorescence imaging systems. Tumor-to-background ratios (TBR) were evaluated. On peak TBR days, probe sensitivity was evaluated. Tumors were stained and imaged microscopically. RESULTS: At peak, closed-field imaging TBR of cetuximab-IRDye800CW (16.8) was significantly greater (P < 0.0001) than Integrisense750 (7.0), Prosense750EX (5.8), and DC101-IRDye800CW (3.7). All agents successfully localized as little as 1.0 mg of tumor tissue in the post-resection bed; cetuximab-IRDye800CW generated the greatest contrast (2.5). Cetuximab-IRDye800CW revealed strong tumor affinity microscopically; tumor fluorescence intensity was significantly greater (P < 0.0004) than 0.2 mm away from tumor border. CONCLUSION: This study demonstrates cetuximab-IRDye800CW superiority. FGS has the potential to improve post-resection morbidity and mortality by improving disease detection.

Abortion law reform: Why ethical intractability and maternal morbidity are grounds for decriminalisation.

In this paper, we present two grounds for arguing that abortion should be decriminalised. First, we consider the implications of the fact that the long-standing ethical debate concerning the morality of abortion has to date proven intractable. We maintain that because the philosophical literature has failed to demonstrate conclusively that views either for or against abortion's moral acceptability are false, the matter remains at a stalemate in terms of rational debate, contributing to the ongoing absence of political and popular consensus about the issue in our society. In these circumstances, we argue, the law should adopt a minimalist position by not imposing criminal sanctions for abortion. Second, we present evidence, often neglected in the moral debates about abortion, that the risks of carrying a fetus to term and of delivery are substantial for a woman. Most laws recognise that, should her life be endangered by her pregnancy, a woman's right to life shall prevail. However, the impacts of carrying a fetus to term and delivery on a woman are not restricted to the risks to her life, but extend to significant permanent changes to her body, and include risks of injury that are not negligible. We argue that a woman should not be compelled to take these risks by laws prohibiting abortion, when no conclusive argument exists against the morality of abortion. We also address, albeit briefly, the issue of late-term abortion.

Donation After the Circulatory Determination of Death: Some Responses to Recent Criticisms.

This article defends the criterion of permanence as a valid criterion for declaring death against some well-known recent objections. We argue that it is reasonable to adopt the criterion of permanence for declaring death, given how difficult it is to know when the point of irreversibility is actually reached. We claim that this point applies in all contexts, including the donation after circulatory determination of death context. We also examine some of the potentially unpalatable ramifications, for current death declaration practices, of adopting the irreversibility criterion.

Determination of death in donation after circulatory death: an ethical propriety.

PURPOSE OF REVIEW: The recently developed donation after circulatory death (DCD) heart transplant technique, pioneered by Papworth Hospital in the UK, involves the use of extracorporeal perfusion technologies to restart the donor heart in situ and thereby restore the donor's own circulation, after first isolating the donor's cerebral circulation. By restoring the circulation in the deceased donor, even if the cerebral circulation is excluded, the Papworth technique challenges the acceptability of death determination in DCD. RECENT FINDINGS: This study uses as its exemplar case the Papworth DCD heart technique to review and make wider comment about death determination in DCD. We seek to answer three challenges to ethical propriety raised by the Papworth technique: death determination using the permanence standard (common to all DCD practice); restoration of heart contractility and circulation in the body; and active prevention of the restoration of brain circulation by use of a cross-clamp to isolate the cerebral circulation. SUMMARY: The Papworth technique for heart DCD does not compromise the permanence standard for declaring death and therefore respects the dead donor rule in the UK, but perhaps elsewhere the law would need to change to refer to the cessation of circulation in the brain.

Advice and care for patients who die by voluntarily stopping eating and drinking is not assisted suicide.

BACKGROUND: A competent patient has the right to refuse foods and fluids even if the patient will die. The exercise of this right, known as voluntarily stopping eating and drinking (VSED), is sometimes proposed as an alternative to physician assisted suicide. However, there is ethical and legal uncertainty about physician involvement in VSED. Are physicians advising of this option, or making patients comfortable while they undertake VSED, assisting suicide? This paper attempts to resolve this ethical and legal uncertainty. DISCUSSION: The standard approach to resolving this conundrum has been to determine whether VSED itself is suicide. Those who claim that VSED is suicide invariably claim that physician involvement in VSED amounts to assisting suicide. Those who claim that VSED is not suicide claim that physician involvement in VSED does not amount to assisting suicide. We reject this standard approach. CONCLUSION: We instead argue that, even if VSED is classified as a kind of suicide, physician involvement in VSED is not a form of assisted suicide. Physician involvement in VSED does not therefore fall within legal provisions that prohibit VSED.

Permanence can be Defended.

In donation after the circulatory-respiratory determination of death (DCDD), the dead donor rule requires that the donor be dead before organ procurement can proceed. Under the relevant limb of the Uniform Determination of Death Act 1981 (USA), a person is dead when the cessation of circulatory-respiratory function is 'irreversible'. Critics of current practice in DCDD have argued that the donor is not dead at the time organs are procured, and so the procurement of organs from these donors violates the dead donor rule. We offer a new argument here in defence of current DCDD practice, and, in particular, of the interpretation of the requirement of 'irreversibility' as permanence.

Numbing of Positive, Negative, and General Emotions: Associations With Trauma Exposure, Posttraumatic Stress, and Depressive Symptoms Among Justice-Involved Youth.

Increasing attention has been drawn to the symptom of emotional numbing in the phenomenology of posttraumatic stress disorder (PTSD), particularly regarding its implications for maladaptive outcomes in adolescence such as delinquent behavior. One change in the definition of emotional numbing according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) was the limitation to the numbing of positive emotions. Previous research with youth, however, has implicated general numbing or numbing of negative emotions in PTSD, whereas numbing of positive emotions may overlap with other disorders, particularly depression. Consequently, the goal of this study was to investigate whether numbing of positive emotions was associated with PTSD symptoms above and beyond numbing of negative emotions, general emotional numbing, or depressive symptoms among at-risk adolescents. In a sample of 221 detained youth (mean age = 15.98 years, SD = 1.25; 50.7% ethnic minority), results of hierarchical multiple regressions indicated that only general emotional numbing and numbing of anger accounted for significant variance in PTSD symptoms (total R(2) = .37). In contrast, numbing of sadness and positive emotions were statistical correlates of depressive symptoms (total R(2) = .24). Further tests using Hayes' Process macro showed that general numbing, 95% CI [.02, .45], and numbing of anger, 95% CI [.01, .42], demonstrated indirect effects on the association between trauma exposure and PTSD symptoms.

We Are Human Beings.

In this paper, I examine Jeff McMahan's arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients.

Acting to let someone die.

This paper examines the recent prominent view in medical ethics that withdrawing life-sustaining treatment (LST) is an act of killing. I trace this view to the rejection of the traditional claim that withdrawing LST is an omission rather than an act. Although that traditional claim is not as problematic as this recent prominent view suggests, my main claim is that even if we accepted that withdrawing LST should be classified as an act rather than as an omission, it could still be classified as letting die rather than killing. Even though omissions are contrasted with acts, letting die need not be, for one can let die by means of acts. The remainder of the paper is devoted to establishing this claim and addresses certain objections to it.

Does withdrawing life-sustaining treatment cause death or allow the patient to die?

This article discusses recent arguments of Franklin Miller and Robert Truog about withdrawal of life-sustaining treatment and causation. The authors argue that traditional medical ethics, and the law, are mistaken to take the view that withdrawal merely allows the patient to die, rather than causing the patient's death, describing such a view as 'patently false'. They argue that the law's continued position to the contrary stems from a moral bias, resulting in the moral and legal fiction that withdrawal does not cause death but lets the patient die. In so arguing, Miller and Truog join a long line of academic criticism of the law that extends back to the seminal decision of Airedale NHS Trust v Bland [1993] AC 789 (HL) and beyond. In this article, I take issue with these claims. I argue that there are reasonable grounds upon which traditional medical ethics and the law can regard withdrawal of life-sustaining treatment as allowing the patient to die rather than causing death, and so the authors' claims that such a view is patently false cannot be sustained. I then tease out the implications of my conclusions for the authors' claim that there is not such a great distinction between withdrawal of life-sustaining treatment, euthanasia, and assisted dying. I conclude by discussing some possible objections to my own view.

The moral status of babies.

In their controversial paper 'After-birth abortion', Alberto Giubilini and Francesca Minerva argue that there is no rational basis for allowing abortion but prohibiting infanticide ('after-birth abortion'). We ought in all consistency either to allow both or prohibit both. This paper rejects their claim, arguing that much-neglected considerations in philosophical discussions of this issue are capable of explaining why we currently permit abortion in some circumstances, while prohibiting infanticide.