A Think Aloud Study Comparing the Validity and Acceptability of Discrete Choice and Best Worst Scaling Methods

Objectives This study provides insights into the validity and acceptability of Discrete Choice Experiment (DCE) and profile-case Best Worst Scaling (BWS) methods for eliciting preferences for health care in a priority-setting context. Methods An adult sample (N = 24) undertook a traditional DCE and a BWS choice task as part of a wider survey on Health Technology Assessment decision criteria. A ‘think aloud’ protocol was applied, whereby participants verbalized their thinking while making choices. Internal validity and acceptability were assessed through a thematic analysis of the decision-making process emerging from the qualitative data and a repeated choice task. Results A thematic analysis of the decision-making process demonstrated clear evidence of ‘trading’ between multiple attribute/levels for the DCE, and to a lesser extent for the BWS task. Limited evidence consistent with a sequential decision-making model was observed for the BWS task. For the BWS task, some participants found choosing the worst attribute/level conceptually challenging. A desire to provide a complete ranking from best to worst was observed. The majority (18,75%) of participants indicated a preference for DCE, as they felt this enabled comparison of alternative full profiles. Those preferring BWS were averse to choosing an undesirable characteristic that was part of a ‘package’, or perceived BWS to be less ethically conflicting or burdensome. In a repeated choice task, more participants were consistent for the DCE (22,92%) than BWS (10,42%) (p = 0.002). Conclusions This study supports the validity and acceptability of the traditional DCE format. Findings relating to the application of BWS profile methods are less definitive. Research avenues to further clarify the comparative merits of these preference elicitation methods are identified

Differential Regulation of Growth-Promoting Signalling Pathways by E-Cadherin

Background: Despite the well-documented association between loss of E-cadherin and carcinogenesis, as well as the link between restoration of its expression and suppression of proliferation in carcinoma cells, the ability of E-cadherin to modulate growth-promoting cell signalling in normal epithelial cells is less well understood and frequently contradictory. The potential for E-cadherin to co-ordinate different proliferation-associated signalling pathways has yet to be fully explored. Methodology/Principal Findings: Using a normal human urothelial (NHU) cell culture system and following a calcium-switch approach, we demonstrate that the stability of NHU cell-cell contacts differentially regulates the Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-Regulated Kinase (ERK) and Phosphatidylinositol 3-Kinase (PI3-K)/AKT pathways. We show that stable cell contacts down-modulate the EGFR/ERK pathway, whilst inducing PI3-K/AKT activity, which transiently enhances cell growth at low density. Functional inactivation of E-cadherin interferes with the capacity of NHU cells to form stable calcium-mediated contacts, attenuates E-cadherin-mediated PI3-K/AKT induction and enhances NHU cell proliferation by allowing de-repression of the EGFR/ERK pathway and constitutive activation of beta-catenin-TCF signalling. Conclusions/Significance: Our findings provide evidence that E-cadherin can differentially and concurrently regulate specific growth-related signalling pathways in a context-specific fashion, with direct, functional consequences for cell proliferation and population growth. Our observations not only reveal a novel, complex role for E-cadherin in normal epithelial cell homeostasis and tissue regeneration, but also provide the basis for a more complete understanding of the consequences of E-cadherin loss on malignant transformation

Development and function of group 2 innate lymphoid cells

The innate lymphoid cell (ILC) family has recently expanded with the discovery of type-2 innate lymphoid cells (ILC2). These cells arise from lymphoid progenitors in the bone marrow and, under the control of the transcriptional regulators RORα and Gata3, they mature to give rise to IL-5, IL-9 and IL-13 producing ILC2. These cells are critical components of the innate immune response to parasitic worm infections and have also been implicated in the pathogenesis of asthma and allergy. Recent advances in our understanding of the molecular regulation of ILC2 development and function now present the opportunity to develop new genetic models to assess ILC2 immune function and to investigate possible therapeutic interventions

An Unusual Case of Acute Scrotal Pain

Patients frequently present to the emergency department with complaints of scrotal or testicular pain. Generally, there is an algorithmic approach to workup, which includes assessment for torsion, infection, or vascular causes, and musculoskeletal causes of pain are also sometimes considered. Spinal cord pathology, however, is less often explored as a cause of testicular pain. Here, we present a case of a 45-year-old man with end-stage renal disease and hypertension who presented with acute testicular pain. After a comprehensive workup, however, the source of pain was not initially found. Progression of the patient\u27s symptoms led to the diagnosis of spontaneous spinal subdural hematoma. This atypical presentation of a rare diagnosis is also interesting due to the patient\u27s concomitant diagnosis of an otherwise asymptomatic COVID-19 infection. While our case represents an atypical combination of clinical features, it also illustrates the importance of continued vigilance and ongoing workup when patients present with severe pain and unclear causes of their symptoms

Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening

Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library preparation have restrictive and/or expensive licenses. Freely available alternatives, though often effective, do not fully account for all possible ionization, tautomeric, and ring-conformational variants. We here present Gypsum-DL, a free, robust open-source program that addresses these challenges. As input, Gypsum-DL accepts virtual compound libraries in SMILES or flat SDF formats. For each molecule in the virtual library, it enumerates appropriate ionization, tautomeric, chiral, cis/trans isomeric, and ring-conformational forms. As output, Gypsum-DL produces an SDF file containing each molecular form, with 3D coordinates assigned. To demonstrate its utility, we processed 1558 molecules taken from the NCI Diversity Set VI and 56,608 molecules taken from a Distributed Drug Discovery (D3) combinatorial virtual library. We also used 4463 high-quality protein-ligand complexes from the PDBBind database to show that Gypsum-DL processing can improve virtual-screening pose prediction. Gypsum-DL is available free of charge under the terms of the Apache License, Version 2.0

The Role of Emotions in Fieldwork: A Self-Study of Family Research in a Corrections Setting

In this study, we document a reflexive process via bracketing techniques and the development of a conceptual map in order to better understand how emotions that arise in the field can inform research design, implementation, and results. We conducted a content analysis of field notes written by a team of researchers who administered an interview to caregivers bringing children to visit an incarcerated family member at a local jail. Our self-examination revealed themes around the team\u27s discomfort connected to the institutional jail setting and intense emotions regarding the life situations of study participants, their treatment by jail staff, and our own concerns about leaving the research setting. We offer recommendations for scholars conducting research in similar environments with vulnerable participants

Rethinking the benefits and costs of childhood vaccination: the example of the Haemophilus influenzae type b vaccine

Economic evaluations of health interventions, such as vaccinations, are important tools for informing health policy. Approaching the analysis from the appropriate perspective is critical to ensuring the validity of evaluation results for particular policy decisions. Using the example of benefit-cost analysis (BCA) of Haemophilus influenzae type b (Hib) vaccination, we demonstrate that past economic evaluations have mostly adopted narrow evaluation perspectives, focusing primarily on health gains, health care cost savings, and reductions in the time costs of caring, while ignoring other important benefits including outcome-related productivity gains (prevention of mental and physical disabilities), behavior-related productivity gains (economic growth due to fertility reductions as vaccination improves child survival), and community externalities (prevention of antibiotic resistance and herd immunity). We further show that the potential cost reductions that could be attained through changes in the delivery of the Hib vaccine have also usually been ignored in economic evaluations. Future economic evaluations of childhood vaccinations should take full account of benefits and costs, so that policy makers have sufficient information to make well-informed decisions on vaccination implementation.Economic evaluation, review, Haemophilus influenzae type b vaccine

Programming Protocol-Independent Packet Processors

P4 is a high-level language for programming protocol-independent packet processors. P4 works in conjunction with SDN control protocols like OpenFlow. In its current form, OpenFlow explicitly specifies protocol headers on which it operates. This set has grown from 12 to 41 fields in a few years, increasing the complexity of the specification while still not providing the flexibility to add new headers. In this paper we propose P4 as a strawman proposal for how OpenFlow should evolve in the future. We have three goals: (1) Reconfigurability in the field: Programmers should be able to change the way switches process packets once they are deployed. (2) Protocol independence: Switches should not be tied to any specific network protocols. (3) Target independence: Programmers should be able to describe packet-processing functionality independently of the specifics of the underlying hardware. As an example, we describe how to use P4 to configure a switch to add a new hierarchical label