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Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

This article discusses the importance of implementing emergency vitrification protocols in IVF laboratories to manage crises and ensure the safety of patients and reproductive material. The article highlights the vulnerability of medical-assisted reproduction due to its dependence on technology, transportation, and a substantial workforce. It also presents a case study from a laboratory in China that successfully implemented emergency vitrification during a flood. The article emphasizes the need for comprehensive emergency disaster management plans, adequate resources, and the skills and adaptability of embryologists in navigating emergencies. It also raises ethical considerations and the importance of proactive planning and collaboration to mitigate risks and uphold the highest standards of care in reproductive medicine. [Extracted from the article]

Large language model (LLM) chatbots possess a remarkable capacity to synthesize complex information into concise, digestible summaries across a wide range of orthopedic subject matter. As LLM chatbots become widely available they will serve as a powerful, accessible resource that patients, clinicians, and researchers may reference to obtain information about orthopedic science and clinical management. Here, we examined the performance of three well‐known and easily accessible chatbots–ChatGPT, Bard, and Bing AI–in responding to inquiries relating to clinical management and orthopedic concepts. Although all three chatbots were found to be capable of generating relevant responses, ChatGPT outperformed Bard and BingAI in each category due to its ability to provide accurate and complete responses to orthopedic queries. Despite their promising applications in clinical management, shortcomings observed included incomplete responses, lack of context, and outdated information. Nonetheless, the ability for these LLM chatbots to address these inquires has largely yet to be evaluated and will be critical for understanding the risks and opportunities of LLM chatbots in orthopedics. [ABSTRACT FROM AUTHOR]

The reaction of protein-bound iron-sulfur (Fe-S) clusters with nitric oxide (NO) plays key roles in NO-mediated toxicity and signaling. Elucidation of the mechanism of the reaction of NO with DNA regulatory proteins that contain Fe-S clusters has been hampered by a lack of information about the nature of the iron-nitrosyl products formed. Herein, we report nuclear resonance vibrational spectroscopy (NRVS) and density functional theory (DFT) calculations that identify NO reaction products in WhiD and NsrR, regulatory proteins that use a [4Fe-4S] cluster to sense NO. This work reveals that nitrosylation yields multiple products structurally related to Roussin's Red Ester (RRE, [Fe2 (NO)4 (Cys)2 ]) and Roussin's Black Salt (RBS, [Fe4 (NO)7 S3 ]. In the latter case, the absence of 32 S/34 S shifts in the Fe-S region of the NRVS spectra suggest that a new species, Roussin's Black Ester (RBE), may be formed, in which one or more of the sulfide ligands is replaced by Cys thiolates.

While video is recognised as an important medium for teaching and learning in the digital age, many video resources are not as effective as they might be, because they do not adequately exploit the strengths of the medium. Presented here are some case studies of video learning resources produced for various undergraduate courses in a university environment. This ongoing project attempts to identify pedagogic strategies for the use of video; learning situations in which video has the most efficacy; and what production techniques can be employed to make effective video learning resources.

Periprosthetic joint infections occur in about 2% of patients who undergo primary total joint arthroplasty, a procedure performed over 1 million times in the United States. The gold standard of treatment is a two‐stage revision. This study aimed to establish a two‐stage procedure in a preclinical small animal model (rat) to test and compare the efficacy of an antibiotic‐eluting material in managing infection. Joint replacement was simulated by transchondylarly implanting a polyethylene (PE) plug into the distal femur and a titanium screw in the proximal tibia. Methicillin‐sensitive Staphylococcus aureus (MSSA) 108 CFU/mL was injected into the tibial canal and the joint space before wound closure. The control groups were killed on postoperative day (POD) 18 (n = 12) and on POD 42 (n = 4) to assess both early and later‐stage outcomes in the control group. The test group underwent revision surgery on POD 18 for treatment using gentamicin‐eluting polyethylene (GPE, n = 4) and was observed until POD 42 to evaluate the efficacy of treatment. Our results showed that the bone loss for the treatment group receiving GPE was significantly less than that of the control (p < 0.05), which was supported by the histology images and an AI‐tool assisted infection rate evaluation. Gait metrics duty factor imbalance and hindlimb temporal symmetry were significantly different between the treatment and control groups on Day 42. This animal model was feasible for evaluating treatments for peri‐prosthetic joint infections (PJI) with a revision surgery and specifically that revision surgery and local antibiotic treatment largely hindered the peri‐prosthetic bone loss. Statement of clinical significance: This revision model of peri‐prosthetic infection has the potential of comparatively evaluating prophylaxis and treatment strategies and devices. Antibiotic‐eluting UHMWPE is devised as at tool in treating PJI while providing weight bearing and joint space preservation. [ABSTRACT FROM AUTHOR]

Bayesian methods have been proposed as a natural fit for pediatric extrapolation, as they allow the incorporation of relevant external data to reduce the required sample size and hence trial burden for the pediatric patient population. In this paper we will discuss our experience and perspectives with these methods in pediatric trials. We will present some of the background and thinking underlying pediatric extrapolation and discuss the use of Bayesian methods within this context. We will present two recent case examples illustrating the value of a Bayesian approach in this setting and present perspectives on some of the issues that we have encountered in these and other cases. [ABSTRACT FROM AUTHOR]

Death metal is the most brutal music in existence. It is a subgenre of music that seeks pure heaviness punctuated by guttural vocalizations more akin to a wounded beast than a human singing lyrics. To the mainstream world, death metal is sometimes misunderstood and enigmatic: how do people listen to such harsh, aggressive music? Death metal fans create a unique corner of fandom, an insular group joined together by a passion for music that is frequently rejected and feared by normative society. This fandom has developed into much more for many fans: it has become a community that has further developed into a world-view. This research aims to argue the theoretical connections between the fandom of death metal music and the studies undertaken through terror management theory (TMT). The central idea of TMT is that our fear of death serves as the primary driver of our actions. The primary aim of this article is to explore the question of how a genre of music that is focused primarily on death serves as a buffer against existentialist dread and considerations of our own mortality? Death metal fandom occupies a unique, dichotomous territory within TMT, as it serves as both a mortality salient (MS) (a threat to the world-views of the mainstream) and a preventative measure against Death Thought Accessibility (thoughts and considerations of our own deaths). Death metal fandom, often vilified by mainstream culture and frequently perceived as a monstrous and violent outlier to normative society, is ironically non-political and not a true threat to the establishment and its tenets. The death metal community does not attack the mainstream, but it is attacked by the mainstream. Threatened by the rejection of beauty and musical normativity exhibited by death metal, the world-view of the mainstream is threatened, causing it to lash out at that which differs from it. This research intends to explore potential assemblages through a mapping of connectives untethered by methodological expectations. It will explore this irony through a developed exploration of death metal fans, the music and the brutality that has helped create a community of fandom that is more supportive and effective at warding off fears of mortality than might initially be expected. [ABSTRACT FROM AUTHOR]

The viscosity of hexagonal close‐packed (hcp) Fe is a fundamental property controlling the dynamics of the Earth's inner core. We studied the rheology of hcp‐Fe using high‐pressure and ‐temperature deformation experiments with in situ stress and strain measurements. Experiments were conducted using D111‐type and deformation‐DIA apparatuses at pressures of 16.3–22.6 GPa, temperatures of 423–923 K, and uniaxial strain rates of 1.52 × 10−6 to 8.81 × 10−5 s−1 in conjunction with synchrotron radiation. Experimental results showed that power‐law dislocation creep with a stress exponent of n = 4.0 ± 0.3, activation energy of E* = 240 ± 20 kJ/mol, and activation volume of V* = 1.4 ± 0.2 cm3/mol is dominant deformation mechanism at >∼800 K, whereas a mechanism with power‐law breakdown prevails at lower temperatures. An extrapolation of the power‐law dislocation creep flow law based on homologous temperature scaling suggests the viscosity of hcp‐Fe under inner core conditions is ≥∼1019 Pa s. If this power‐law dislocation creep mechanism is assumed to be the dominant mechanism in the Earth's inner core, the equatorial growth or translation mode mechanism may be the dominant geodynamical mechanism causing the observed inner core structure. Plain Language Summary: Although many geodynamic mechanisms have been proposed regarding the origin of the observed complex structure of Earth's inner core, no clear consensus has been reached. This is partly owing to the lack of accurate knowledge of the viscosity in the inner core, which is believed to mostly comprise of hexagonal close‐packed Fe (hcp‐Fe). Here, we studied the viscosity of hcp‐Fe using high‐pressure and high‐temperature deformation experiments. The results showed that the dominant deformation mechanism in hcp‐Fe changes depending on the temperature, with power‐law dislocation creep and low‐temperature creep being most important above and below ∼800 K, respectively. Based on extrapolation of these experimental results we estimate the inner core viscosity to be ≥1019 Pa s. This inner core viscosity suggests the equatorial growth or translation mode model as the dominant geodynamical mechanism in the Earth's inner core. Key Points: We studied rheology of hexagonal close‐packed Fe based on high‐pressure and high‐temperature deformation experimentsDominant deformation mechanism was power‐law dislocation creep at temperatures above ∼800 KWe estimated the viscosity of hexagonal close‐packed Fe under inner core conditions as ≥∼1019 Pa s [ABSTRACT FROM AUTHOR]