The structure of analogical reasoning in bioethics.

Casuistry, which involves analogical reasoning, is a popular methodological approach in bioethics. The method has its advantages and challenges, which are widely acknowledged. Meta-philosophical reflection on exactly how bioethical casuistry works and how the challenges can be addressed is limited. In this paper we propose a framework for structuring casuistry and analogical reasoning in bioethics. The framework is developed by incorporating theories and insights from the philosophy of science: Mary Hesse's ideas on horizontal and vertical relations in analogical reasoning in the sciences, Paul Bartha's articulation model of analogical reasoning and Daniel Steel's insights on mechanism-based extrapolation in biomedical research. Adopting our framework results in two practical benefits: it sets methodological standards for analogical reasoning and enables us to compare and evaluate diverging lines of analogical reasoning in a systematic way. Adopting the framework also has theoretical benefits: it helps to understand how analogical reasoning can have moral normativity; it pinpoints exactly where moral principles or theories enter analogical reasoning; and it helps to understand why casuistry is an attractive method in bioethics and in applied ethics more generally.

Preserved periprosthetic bone stock at 5 years post-operatively with uncemented short hip stem in both collared and collarless version.

INTRODUCTION: Previous bone density studies have generally shown bone resorption around both cemented and uncemented total hip arthroplasty (THA) stems. This is presumed to be due to stress shielding. Short stems have been introduced partly to preserve bone in the proximal femur by a more physiological loading of the bone. The purpose of this study was to evaluate bone remodeling around a short, fully hydroxyapatite-coated titanium stem that comes in a collared and collarless version. PATIENTS AND METHODS: A prospective cohort of 50 patients included in a study evaluating the Furlong Evolution stem has been followed for 5 years. Examination was done with dual energy X-ray absorptiometry (DXA) postoperatively, at 1, 2 and 5 years. Clinical outcome was followed with radiography and both general and hip specific outcome measures. RESULTS: The two versions of the stem behaved similarly regarding bone remodeling. After an initial decrease up to 1 year, bone mineral density (BMD) increased in all Gruen zones up to 2 years and at 5 years bone stock was still preserved compared with postoperatively (net BMD + 1.2% (95% CI - 0.4 to 2.8)). Increase in BMD occurred mainly in the greater trochanter and distally around the stem with a decrease in the calcar area. Both versions showed excellent clinical outcome up to 5 years. CONCLUSION: This short stem seems to preserve proximal bone stock up to 5 years, exhibiting similar behaviour both with and without a collar. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov, (identifier: NCT01894854). July 10, 2013.

Micrographic Surgery Allows Fascia Preservation in Dermatofibro-sarcoma Protuberans.

Removal of the deep fascia is recommended in therapy for dermatofibrosarcoma protuberans, but its necessity in the context of micrographic surgery is unclear. A retrospective clinicopathological analysis of 48 patients with dermatofibrosarcoma protuberans treated by micrographic surgery was performed, to determine in which tumours fascia preservation was feasible and safe. Histologically, 93% of tumours on the trunk and extremities and 14% of tumours in the head and neck region were fully located above the fascia. Localization on the head and neck was the only significant risk factor for tumour extension beyond the subcutis (p<0.001). Overall, 44% of tumours were completely excised above the fascia and 56% with deeper excisions. Two deeply infiltrating tumours (4%) on the head recurred, but in none of these lesions was the fascia spared. These results show that micrographic surgery allows fascia preservation in superficial tumours outside the head and neck region.

The Structure of Causal Explanations in Population Biology.

The scope of this paper can be clarified by means of a well-known phenomenon that is usually called 'industrial melanism': the fact that the melanic form of the peppered moth became dominant in industrial areas in England in the second half of the nineteenth century. Such changes in relative phenotype frequencies are important explananda for population biologists. Apart from trying to explain such changes over time, population biologists also often try to explain differences between populations, e.g. why yellow shell colour is dominant in certain colonies of land snails and almost absent in other colonies. The causal explanations that are given to address such explananda are the objects of analysis in this paper. Our primary aim is to explicate their structure: we want to capture the typical ingredients of causal explanations in population biology, and their organisation. Based on this explication, we discuss how natural selection fits into recent mechanical philosophy of science, and engage in the debate on the nature of evolutionary theory.

Is a hollow centralizer necessary when using a polished, tapered, cemented femoral stem?

Background and purpose - A tapered, polished and collarless stem is normally equipped with a hollow centralizer to prevent the stem from becoming end-bearing in the cement as the stem subsides. In a randomized clinical trial, we evaluated such a stem (MS-30), which was initially introduced with a solid centralizer but was later recommended to be fitted with a hollow centralizer. We hypothesized that while the stem would sink more, it would become rotationally stable and have less retroversion with a hollow centralizer than with a solid centralizer. Patients and methods - We randomized 60 patients with primary hip arthritis to receive either a hollow centralizer or a solid centralizer with the stem. The effect was evaluated over a 10-year follow-up period with repeated RSA examinations, conventional radiographs, and clinical follow-ups using the WOMAC and SF-12 questionnaires. Results - At 10-year follow-up, the group with hollow centralizers had subsided more than the group with solid centralizers (1.99 mm (hollow) as opposed to 0.57 mm (solid); p < 0.001). However, rotation was similar at 10-year follow-up (mean retroversion 1.34° (hollow) and 1.30° (solid)). Both groups showed excellent 10-year results, with similar clinical outcome, and none of the stems were radiographically loose or had been revised. Interpretation - As expected, there was more subsidence in the group with hollow centralizers, and with similar magnitude to that reported in earlier RSA studies on conceptually similar prostheses. Interestingly, there was no difference in the rotational behavior of the prostheses. This stem type appears to have a design that, regardless of the type of centralizer and the possibility of subsidence, withstands the rotational forces it is subjected to very well. This study does not support the need for a hollow centralizer for these types of stems.

The role of orientation experiments in discovering mechanisms.

Many types of experiments have been recognized in the literature. One important type we discuss in this article is the orientation experiment. While orientation experiments are like other types of experiments in that they are tests for causal relevance, they also have other qualities. One important (but not the only) goal of these experiments is to offer a rough, qualitative characterization of the mechanism responsible for a capacity of interest, effectively constraining future research. This makes them particularly useful during the early stages of investigation, when an explanandum-phenomenon has just been identified and several (often competing) hypotheses as to the qualitative character of the mechanism responsible for it are proposed. We illustrate our claims, and explicate a number of additional aims that orientation experiments can sometimes serve, by considering three case studies from different era's, namely the discovery of the mechanisms responsible for i) the capacity of eels to produce numbing sensations (17th and 18th century), ii) puerperal fever in Semmelweis' Vienna Maternity Hospital (19th century), and iii) the capacity of pigeons to home (20th century).

Design modifications of the uncemented Furlong hip stem result in minor early subsidence but do not affect further stability: a randomized controlled RSA study with 5-year follow-up.

BACKGROUND AND PURPOSE: Even small design modifications of uncemented hip stems may alter the postoperative 3-D migration pattern. The Furlong Active is an uncemented femoral stem which, in terms of design, is based on its precursor-the well-proven Furlong HAC-but has undergone several design changes. The collar has been removed on the Active stem along with the lateral fin; it is shorter and has more rounded edges in the proximal part. We compared the migration patterns of the uncemented Furlong HAC stem and the modified Furlong Active stem in a randomized, controlled trial over 5 years using radiostereometry (RSA). PATIENTS AND METHODS: 50 patients with primary osteoarthritis were randomized to receive either the HAC stem or the Active stem. The patients underwent repeated RSA examinations (postoperatively, at 3 months, and after 1, 2, and 5 years) and conventional radiography, and they also filled out hip-specific questionnaires. RESULTS: During the first 3 months, the collarless Active stem subsided to a greater extent than the collar-fitted HAC stem (0.99 mm vs. 0.31 mm, p=0.05). There were, however, no other differences in movement measured by RSA or in clinical outcome between the 2 stems. After 3 months, both stem types had stabilized and almost no further migration was seen. INTERPRETATION: The Active stem showed no signs of unfavorable migration. Our results suggest that the osseointegration is not compromised by the new design features.

Distal Flow Diversion with Anti-Thrombotically Coated and Bare Metal Low-Profile Flow Diverters-A Comparison.

BACKGROUND AND PURPOSE: The establishment of low-profile flow diverting stents (FDS), for example, the Silk Vista Baby (SVB) and the p48MW, facilitated endovascular treatment of peripheral cerebral aneurysms. This study therefore aims to compare the performance and outcomes of the SVB with those of the p48MW HPC, with a special focus on hemodynamic aspects of peripheral segments and bifurcations. MATERIALS AND METHODS: The study cohort comprises 108 patients, who were either treated with the SVB or the p48MW HPC between June 2018 and April 2021. RESULTS: Sixty patients received a SVB and forty-eight patients a p48MW HPC. The SVB was used predominantly in the AcomA-complex, and the p48MW HPC in the MCA bifurcation. Immediately after implantation, significant hemodynamic downgrading (OKM A2-A3, B1-B3, C3) was achieved in 60% in the SVB group vs. 75.1% in the p48MW HPC group. At the second follow-up, after an average of 8.8 and 10.9 months, respectively, OKM D1 was observed in 64.4% of the SVB group vs. 27.3% in the p48MW HPC group. Only 1.7% vs. 6.8% of the aneurysms remained morphologically unaltered (OKM A1). Adverse events with persisting neurologic sequalae at last follow-up were largely comparable in both groups (5.0% vs. 4.2%). CONCLUSION: Immediately after implantation, the p48MW HPC had a more profound hemodynamic impact than the SVB; however, early complete occlusions were achieved in a greater proportion of lesions after implantation of the uncoated SVB.

Migration pattern of a short uncemented stem with or without collar: a randomised RSA-study with 2 years follow-up.

BACKGROUND: There is an increasing interest in shorter, proximally loading, uncemented femoral stems. The aim of this study was to evaluate a new short stem type, its design based on a well-proven precursor, but with several new design features to facilitate easier insertion and possible preservation of proximal bone stock. It is available with or without a collar. METHODS: The study includes 50 patients with primary osteoarthritis, mean age 59 (range 36-75) years, randomised to receive either the collar-fitted or the collarless stem. The patients underwent repeated radiostereometry (RSA) examinations (0, 0.5, 3, 12, 24 months), conventional radiography and filled out both hip-specific (HOOS) and general health (EQ-5D) questionnaires. RESULTS: There was no statistically significant difference between the collared and collarless stems regarding migration and clinical outcome. Both stem types exhibit a similar pattern of initial subsidence (collared 0.63 mm vs. collarless 0.75 mm [p = 0.50]) and retroversion (collared 0.71° vs. collarless 0.97° [p = 0.36]) up to 3 months followed by stabilisation, in similarity with its precursors, suggesting good osseointegration. No stem has been revised or considered loose. CONCLUSIONS: The new design features, including shortening the stem, do not compromise migration pattern or osseointegration, regardless collar or not.

Endovascular Treatment of Intracranial Aneurysms in Small Peripheral Vessel Segments-Efficacy and Intermediate Follow-Up Results of Flow Diversion With the Silk Vista Baby Low-Profile Flow Diverter.

Background and Purpose: Low-profile flow diverter stents (FDS) quite recently amended peripheral segments as targets for hemodynamic aneurysm treatment; however, reports on outcomes, especially later than 3 months, are scarce. This study therefore reports our experience with the novel silk vista baby (SVB) FDS and respective outcomes after 8 and 11 months with special respect to specific adverse events. Materials and Methods: Forty-four patients (mean age, 53 years) harboring 47 aneurysms treated with the SVB between June 2018 and December 2019 were included in our study. Clinical, procedural, and angiographic data were collected. Follow-ups were performed on average after 3, 8, and 11 months, respectively. Treatment effect was assessed using the O'Kelly Marotta (OKM) grading system. Results: Overall, angiographic follow-ups were available for 41 patients/45 aneurysms. Occlusion or significant reduction in aneurysmal perfusion (OKM: D1, B1-B3 and A2-A3) was observed in 98% of all aneurysms after 8 months. Only 2% of the treated aneurysms remained morphologically unaltered and without an apparent change in perfusion (OKM A1). Adverse events in the early post-interventional course occurred in seven patients; out of them, mRS-relevant morbidity at 90 days related to FDS treatment was observable in two patients. One death occurred in the context of severe SAH related to an acutely ruptured dissecting aneurysm of the vertebral artery. Conclusion: The SVB achieves sufficient occlusion rates of intracranial aneurysms originating from peripheral segments, which are comparable to prior established conventional FDS with acceptably low complication rates. However, alteration of a hemodynamic equilibrium in distal localizations requires special attention to prevent ischemic events.

Inferential explanations in biology.

Among philosophers of science, there is now a widespread agreement that the DN model of explanation is poorly equipped to account for explanations in biology. Rather than identifying laws, so the consensus goes, researchers explain biological capacities by constructing a model of the underlying mechanism. We think that the dichotomy between DN explanations and mechanistic explanations is misleading. In this article, we argue that there are cases in which biological capacities are explained without constructing a model of the underlying mechanism. Although these explanations do not conform to Hempel's DN model (they do not deduce the explanandum from laws of nature), they do invoke more or less stable generalisations. Because they invoke generalisations and have the form of an argument, we call them inferential explanations. We support this claim by considering two examples of explanations of biological capacities: pigeon navigation and photoperiodism. Next, we will argue that these non-mechanistic explanations are crucial to biology in three ways: (i) sometimes, they are the only thing we have (there is no alternative available), (ii) they are heuristically useful, and (iii) they provide genuine understanding and so are interesting in their own right. In the last sections we discuss the relation between types of explanations and types of experiments and situate our views within some relevant debates on explanatory power and explanatory virtues.

Explanatory pluralism in the medical sciences: theory and practice.

Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise.