bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances and Prospects of Small Molecular Organic Thermoelectric Materials
Authors: Zhou Dan , Zhang Hehui , Zheng Haolan , Xu Zhentian , Xu Haitao , Guo Huilong , Li Peining , Tong Yongfen , Hu Bin , Chen Lie
Published: March 2022

Thermoelectric (TE) materials possess unique energy conversion capabilities between heat and electrical energy. Small organic semiconductors have aroused widespread attention for the fabrication of TE devices due to their advantages of low toxicity, large area, light weight, and easy fabrication. However, the low TE properties hinder their large‐scale commercial application. Herein, the basic knowledge about TE materials, including parameters affecting the TE performance and the remaining challenges of the organic thermoelectric (OTE) materials, are initially summarized in detail. Second, the optimization strategies of power factor, including the selection and design of dopants and structural modification of the dope‐host are introduced. Third, some achievements of p‐ and n‐type small molecular OTE materials are highlighted to briefly provide their future developing trend; finally, insights on the future development of OTE materials are also provided in this study.
Inverse Material Search and Synthesis Verification by Hand Drawings via Transfer Learning and Contour Detection
Authors: Serov Nikita , Vinogradov Vladimir
Published: March 2022

Nano‐ and micromaterials of various morphologies and compositions have extensive use in many different areas. However, the search for procedures giving custom nanomaterials with the desired structure, shape, and size remains a challenge and is often implemented by manual article screening. Here, for the first time, scanning and transmission electron microscopy inverse image search and hand drawing‐based search via transfer learning are developed, namely, VGG16 convolution neural network repurposing for image features extraction and image similarity determination. Moreover, the case use of this platform is demonstrated on the calcium carbonate system, where the data are acquired by random high throughput experimental synthesis, and on Au nanoparticles data extracted from the articles. This approach can be used for advanced nanomaterials search, synthesis procedure verification, and can be further combined with machine learning solutions to provide data‐driven nanomaterials discovery.
Extraordinary Ordovician trilobite Fantasticolithus gen. nov. from Peru and its bearing on the trinucleimorph hypothesis
Authors: Fortey Richard A. , Gutiérrez‐Marco Juan C.
Published: March 2022

Fantasticolithus isabelae, a new genus and species of trinucleid trilobite from the Lower Ordovician of Peru, developed anterior ventral cephalic ‘props’ that are unique in the Trilobita. Its broad and finely pitted genal prolongations are unlike those of any previously known trinucleid, and closely resemble those invariably present in the unrelated Family Harpetidae, supporting the hypothesis that the two families shared a similar mode of life, as ‘trinucleimorphs’. Fantasticolithus was probably derived from an early trinucleid with a marginal girder, although it resembles younger genera such as Marrolithus in its enlarged anterolateral pits. The new genus provides a natural experiment to test the hypothesis of trinucleimorphs as filter feeders that used a ventral feeding chamber. The role of the pitted marginal fringe as an egress for feeding currents is discussed. Fantasticolithus had an unusual anterior vent that provided a simpler exit mechanism for feeding currents than the pitted fringe. However, the pits were probably important for trinucleids that lacked an anterior arch.
Effects of mokuboito, a Japanese Kampo medicine, on long‐term clinical outcomes in patients with heart failure
Authors: Ezaki Hirotaka , Ayaori Makoto , Sato Hiroki , Sakurada Masami
Published: March 2022

Aim

We previously reported that oral administration of mokuboito (a Japanese Kampo medicine) significantly improved symptoms in hospitalized patients with heart failure (HF). However, it remains unclear whether mokuboito treatment affects the long‐term clinical prognosis in patients with HF.

Methods

We retrospectively investigated the long‐term prognosis in 40 patients who participated in our previous study. Patients were allocated randomly to Group S (standard therapy alone) or Group M (oral administration of mokuboito plus standard therapy). The primary outcome was the composite endpoint of major adverse cardiovascular events (MACE; death from any cause, myocardial infarction or unstable angina, and readmission due to worsening HF) during 2 years.

Results

MACE were respectively observed in 13 and 5 patients in Group S and Group M (incidence rate per 100 person‐years, 57.7 versus 17.3; P = 0.02), and the hazard ratio (HR) was 0.32 (95% CI 0.12–0.91; P = 0.02). Death from any cause was respectively observed in seven and three patients in Group S and Group M (incidence rate per 100 person‐years, 22.6 versus 9.00; P = 0.18), and the HR was 0.41 (95% CI 0.11–1.58; P = 0.18). Readmission due to worsening HF was respectively observed in 11 and 5 in Group S and Group M (incidence rate per 100 person‐years, 44.4 versus 16.8; P = 0.08), and the HR was 0.39 (95% CI 0.13–1.12; P = 0.07).

Conclusions

Oral administration of mokuboito significantly improved long‐term clinical outcomes in patients hospitalized for HF during 2 years after discharge.
MicroRNA‐455‐3p functions as a tumor suppressor by targeting HDAC2 to regulate cell cycle in hepatocellular carcinoma
Authors: Ma Fuquan , Huang Jin , Li Weizhi , Li Peijie , Liu Mengying , Xue Hui
Published: March 2022

Hepatocellular carcinoma (HCC) is one of the most common cancers. MicroRNA has been studied more and more deeply and may become a new target for the treatment of HCC. Here, we investigated the role of miR‐455‐3p in HCC progression. Compared with non‐tumor tissues and normal human hepatic cells, miR‐455‐3p expression was significantly downregulated in HCC tissues and cell lines. And overexpression of miR‐455‐3p inhibited cell proliferation and migration but promoted cell apoptosis in HCC cell lines HepG2 and Huh7. Mechanism studies displayed that miR‐455‐3p targeted HDAC2 and negatively regulated HDAC2 expression. Moreover, HDAC2 was highly expressed in HCC tissues and cell lines. Overexpression of HDAC2 reversed the inhibitory effects of miR‐455‐3p on cell proliferation, migration and cell cycle protein (CDK6 and cyclin D1) expression, and neutralized the promotion effects of miR‐455‐3p on cell apoptosis and the activation of p53 pathway. Furthermore, a p53 inhibitor Pifithrin‐α (PFT‐α) effectively abolished the effects of miR‐455‐3p on HCC cell behaviors. Additionally, the role of miR‐455‐3p in tumorigenesis was evaluated by using a mouse xenograft model, and the data showed that miR‐455‐3p suppressed tumor growth in vivo. In summary, our results suggested that miR‐455‐3p targeted HDAC2 to inhibit cell proliferation, migration and promote cell apoptosis via the activation of p53 pathway.
Application of predictive models in boosting power of Alzheimer's disease clinical trials: A post hoc analysis of phase 3 solanezumab trials
Authors: Ezzati Ali , Davatzikos Christos , Wolk David A. , Hall Charles B. , Habeck Christian , Lipton Richard B.
Published: March 2022

Background

The ideal participants for Alzheimer's disease (AD) clinical trials would show cognitive decline in the absence of treatment (i.e., placebo arm) and would also respond to the therapeutic intervention.

Objective

To investigate if predictive models can be an effective tool for identifying and excluding people unlikely to show cognitive decline as an enrichment strategy in AD trials.

Method

We used data from the placebo arms of two phase 3, double‐blind trials, EXPEDITION and EXPEDITION2. Patients had 18 months of follow‐up. Based on the longitudinal data from the placebo arm, we classified participants into two groups: one showed cognitive decline (any negative slope) and the other showed no cognitive decline (slope is zero or positive) on the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS‐cog). We used baseline data for EXPEDITION to train regression‐based classifiers and machine learning classifiers to estimate probability of cognitive decline. Models were applied to EXPEDITION2 data to assess predicted performance in an independent sample. Features used in predictive models included baseline demographics, apolipoprotein E ε4 genotype, neuropsychological scores, functional scores, and volumetric magnetic resonance imaging.

Result

In EXPEDITION, 46.3% of placebo‐treated patients showed no cognitive decline and the proportion was similar in EXPEDITION2 (45.6%). Models had high sensitivity and modest specificity in both the training (EXPEDITION) and replication samples (EXPEDITION2) for detecting the stable group. Positive predictive value of models was higher than the base prevalence of cognitive decline, and negative predictive value of models were higher than the base rate of participants who had stable cognition.

Conclusion

Excluding persons with AD unlikely to decline from the active and placebo arms of clinical trials using predictive models may boost the power of AD trials through selective inclusion of participants expected to decline.
Faecal microbiota transplantation for the treatment of acute haemorrhagic diarrhoea syndrome in two dogs
Authors: Wen Tsung Fei , Cho Ying Chu , Li Chia Yin
Published: March 2022

A 2‐year‐old, male, entire mixed breed dog and a 10‐year‐old, spayed, female mixed breed dog were presented for acute onset of bloody diarrhoea and hypovolaemic shock. Faecal microbiota transplantation was introduced in addition to antibiotics and supportive care after resuscitation. Faecal condition improved after treatment, and both dogs recovered within 3 weeks.
Identifying potential paraben transformation products and evaluating changes in toxicity as a result of transformation
Authors: Penrose Michael T. , Cobb George P.
Published: March 2022

Parabens are a class of compounds often used as preservatives in personal care products, pharmaceuticals, and food. They have received attention recently due to findings that demonstrate estrogenic impacts and other adverse effects of parabens. Release into wastewater effluent is considered a major contributor to the spread of parabens into surface water. Current regulations in areas such as Japan, Europe, and Southeast Asia limit the concentrations of parabens that can be used in formulations but do not address concentrations discharged into waterbodies. Recent studies suggest that parent parabens are effectively eliminated by transformation during the wastewater treatment processes. Common tertiary treatments include ultrafiltration, chlorination, UV disinfection and ozonation. Ultrafiltration is used to remove solids before a disinfection step. Of the disinfection steps, ozonation is often the most effective at removing parabens. Not much is known about the toxicities of paraben transformation products. Of the transformation products, chlorinated parabens and PHBA are the most studied. Previous studies have shown that chlorinated parabens have greatly reduced estrogen agonistic activity when compared with the activity of parents. However, more recent studies have found that halogenated parabens actually have estrogen antagonistic activity. Further research involving chlorinated parabens could include other toxic endpoints. No known studies have evaluated adverse effects of oxygenated parabens. Parabens can interact with chlorine residues in the environment and form chlorinated products, this will occur at a faster rate during chlorination. Ozonation will oxidize parabens and UV disinfection can both oxidize and halogenate parabens. All studies determining potential transformation products have been done in laboratory settings or specific conditions. Further research is needed to determine if these transformations occur in situ.

Practitioner Points

Common chemical processes utilized by wastewater treatment facilities are effective at transforming parabens.

Paraben transformation products are released in greater concentration in effluent than parent paraben compounds.

Halogenated transformation products have been identified as estrogen receptor antagonists.
Time-Domain Fluorescence Lifetime Imaging of cAMP Levels with EPAC-Based FRET Sensors
Authors: Kukk Olga , Klarenbeek Jeffrey , Jalink Kees
Published: March 2022

Second messenger molecules in eukaryotic cells relay the signals from activated cell surface receptors to intracellular effector proteins. FRET-based sensors are ideal to visualize and measure the often rapid changes of second messenger concentrations in time and place. Fluorescence Lifetime Imaging (FLIM) is an intrinsically quantitative technique for measuring FRET. Given the recent development of commercially available, sensitive and photon-efficient FLIM instrumentation, it is becoming the method of choice for FRET detection in signaling studies. Here, we describe a detailed protocol for time domain FLIM, using the EPAC-based FRET sensor to measure changes in cellular cAMP levels with high spatiotemporal resolution as an example.
Recent Directions in the Regulation of Insurance Claims Handling in the United Kingdom and Australia: A Model for Other Jurisdictions to Consider?
Authors: Bowley Robin
Published: March 2022

This chapter examines recent developments in the regulation of insurance claims handling in the United Kingdom and in Australia. It commences by reviewing the relevant Insurance Core Principles developed by the International Association of Insurance Supervisors which articulate the standards that national supervisors should implement to effectively regulate the handling of claims and the resolution of disputes with policyholders. From this basis, it then examines the various rules developed by the Financial Conduct Authority to regulate claims handling in the United Kingdom, and through the use of case studies discusses how compliance with these rules has been monitored and enforced. The chapter then examines the legal framework for regulating insurance claims handling in Australia, which has been significantly expanded following the implementation of the reforms recommended by the 2019 Royal Commission into Misconduct in the Banking, Superannuation and Financial Services Industry. The chapter concludes that the approaches adopted in these two jurisdictions could provide a model for similar jurisdictions considering similar regulatory challenges.
The Role of the Compliance Function in the Process of Managing the Risk of Non-Compliance in an Insurance Undertaking
Authors: Paś Wojciech
Published: March 2022

This chapter is devoted to the role and significance of the compliance function in an insurance undertaking. This chapter presents selected models of compliance functions in European insurance undertakings. The main assumption of the chapter was an attempt to determine the importance of the compliance function in the process of managing the risk of non-compliance by means of the functioning and organisation of this unit within the structures of an insurance undertaking.
Insurance Outsourcing: A Legal Analysis
Authors: Szaraniec Monika
Published: March 2022

Outsourcing plays an important role in the operation of insurance and reinsurance companies. This article aims to define the legal conditions of insurance outsourcing and their evaluation by the author. The example of limiting the scope of outsourcing in the activities of insurance and reinsurance companies in the Polish law shows its specificity compared to other outsourcing in business. This specificity lies primarily in the need to control insurance outsourcing by the EU and national supervisory authorities. There is a tendency in the law to extend the regulations related to insurance outsourcing to the further performance of a process, service or activity by insurance companies, particularly in the field of cooperation of traditional distributors withInsurtech. The lack of legal regulations forces EIOPA to look for appropriate and effective legal solutions in the field of supervision over insurance outsourcing. This process is mainly based on self-regulation of the market through ‘soft law’—this practice sets new tasks for the EU and national regulators.
Corporate Governance Standards for Insurers in Singapore
Authors: Chen Christopher
Published: March 2022

This chapter examines the corporate governance regime for insurers in Singapore. Singapore aims to be a global hub for insurance and reinsurance in the Asia Pacific region, and as an international financial centre it currently hosts a mixture of local and international insurers and reinsurers serving different market sectors. However, the domestic insurance market is small, and insurers registered in Singapore come from many countries and provide products and services to many businesses and individuals outside the city-state. This presents challenges to the sole financial regulator, the Monetary Authority of Singapore (MAS), in implementing and enforcing corporate governance standards on various (re)insurers, many of which are part of larger overseas insurance groups. What should be the way to impose corporate governance standards on various types of (re)insurers? This chapter addresses these questions in the context of Singapore. The general regulatory concerns over corporate governance standards and Singapore’s corporate governance regimes for insurers are first introduced. Specific corporate governance issues are then examined, including the implementation of standards for non-domestic insurers or a branch or subsidiary of a larger insurance group from overseas, and the governance of captive insurers and reinsurers. Singapore’s approach is then discussed and the effectiveness of corporate governance regulations for insurers is assessed. Empirical evidence is presented when data are available.
Recovery and Resolution of Insurance Companies and Director’s Duties
Authors: Siri Michele , Van den Hurk Arthur
Published: March 2022

In this chapter, largely finalised before the presentation of a legislative proposal for a European Insurance Recovery and Resolution Directive, on September 2021, recovery and resolution frameworks of insurance companies and insurance groups are discussed. Currently, the insurance regulatory framework at the European level (Solvency II) does not contain a fully developed framework with respect to recovery and (orderly) resolution such as the Bank Recovery & Resolution Directive and the Single Resolution Mechanism. Recent developments at the international level on the initiative of the Financial Stability Board and International Association of Insurance Supervisors are discussed. It is the expectation that the Solvency II 2020 review will introduce minimum harmonising regulatory standards at the European level with respect to the recovery and resolution of insurers. In this chapter, the assumption is made that the legislative proposal of the European Commission will be based on the technical advice, provided by EIOPA in the context of the Solvency II 2020 review. Therefore, this chapter discusses this technical advice in some detail. Recovery and resolution frameworks, particularly ex-ante planning, requires insurance companies and insurance groups to expand their focus from the regular going concern focus to adverse circumstances, including the ability to recover and to be resolved in orderly manner. The chapter assesses the consequences this change of focus might have on the governance of insurance companies and groups.
Restructuring, Winding-Up & Portfolio Transfer of Insurance Companies in Distress
Authors: Noussia Kyriaki , Underwood Peter , Frastanlis Stergios
Published: March 2022

Insurance companies often need to go through restructuring for various reasons. Such restructuring can happen in company law through the mechanism of M&A, or under EU legislation via portfolio transfer (see e.g. Article 14 of Directive 2002/83/EC and Article 12 of Directive 92/49/EEC in the field of non-life insurance). This chapter discusses reorganising, restructuring and winding-up of insurance companies, as well as insurance portfolio transfers by means of company law mechanisms (M&A) and under the Cross-Border Mergers Directive, as well as under the Solvency II Directive. It then goes on to discuss the position under Greek law, and uses as a case study the winding-up of Aspis Pronia in 2009 and the transfer of the insurance undertakings’ portfolios. The analysis will allow us to identify that the level of insurance portfolio transfers harmonisation in the EU is not as high as expected, and that a common framework and harmonisation is needed.
Insurance in M&A Transactions
Authors: Borselli Angelo
Published: March 2022

Mergers and acquisitions (M&A) involve transactional risks, no matter how extensive and accurate the due diligence process is. This raises the question as to how transacting parties can be protected. Representations and warranties and indemnification provisions as well as escrow requirements, typically included in the acquisition agreement, may often prove to be inefficient and inadequate to this end. When negotiating these terms, transacting parties clearly have contrasting interests, and there could also be cases, especially in public company transactions or distressed sales, where the buyer may have no effective remedies against the seller after the closing.

To overcome problems associated with seller’s indemnities, transacting parties increasingly avail themselves of some innovative insurance products, generally known under the catch-all name of “transactional insurance,” that provide coverage for risks arising out of extraordinary corporate transactions, including risks related to breaches of representations and warranties, tax liabilities, pending or potential litigation and other contingent liabilities.

This chapter explores the role that insurance can play in managing transactional risk, discussing whether it may represent an efficient alternative to more traditional, contractual solutions like indemnity and escrow requirements. The discussion suggests that transactional insurance can serve as an effective risk-transfer tool in M&A, which may act as a supplement or also a substitute for seller indemnity obligations. By spreading transactional risk, insurance can facilitate M&A transactions and enhance the overall social benefit, providing economic security at a fraction of the cost that it would take for transacting parties to protect themselves. No problems of adverse selection or moral hazard peculiar to the M&A context seem to arise and a steadily increasing use of insurance in M&A can be expected.
Conceptual Background
Authors: Pfoser Sarah
Published: March 2022

The following chapter establishes the conceptual background for this thesis. First, the construct acceptance will be defined in Subchapter 0 since this term is used ambiguously in the literature. Studying the acceptance of sustainable freight transport revealed that there are different stages of acceptance which involve a varying degree of commitment by transport users. In context of this thesis, acceptance refers to the stages of willingness to use or the actual use of sustainable freight transport strategies. Afterwards, a definition and classification of policy measures is given in Subchapter 2.2. The common sticks-carrots-sermons typology is presented, which involves three main types of measures, namely regulation (“sticks”), economic incentives (“carrots”) and information instruments (“sermons”).
Strategies for Sustainable Freight Transport
Authors: Pfoser Sarah
Published: March 2022

The case of three different strategies for sustainable freight transport is studied in the thesis: (1) horizontal collaboration in a Physical Internet network, (2) multimodal freight transport and (3) liquefied natural gas (LNG) as alternative truck fuel. Each of these three strategies falls within a different pillar of the avoid-shift-reduce framework. Chapter 4 introduces the ASI (avoid-shift-improve) framework and gives an overview of existing strategies for sustainable freight transport. In particular, horizontal collaboration in a PI network, multimodality and LNG as an alternative fuel will be presented and differentiated from similar concepts. It will be justified why these three particular strategies have been chosen as the subject of this thesis.
Policy Measures to Promote Sustainable Freight Transport
Authors: Pfoser Sarah
Published: March 2022

In the following chapter, policy measures are developed which encourage transport users to implement sustainable freight transport. First, organizational theories are used to provide theoretical insights on how to stimulate the use of sustainable practices in Subchapter 6.1. These organizational theories are merged into a theoretical framework which supports the development of policy measures for sustainable freight transport. A fundamental goal of policy measures is to eliminate market failures. Subchapter 6.2 explains which market failures occur in the area of sustainable freight transport and should be addressed by policy measures. Afterwards, a set of user-centric policy measures is presented in Subchapter 6.3 to promote sustainable freight transport. A new classification scheme is suggested to categorize the user-centric policy measures, namely carrots, means and sermons.
White and brown adipose tissue functionality is impaired by fine particulate matter (PM2.5) exposure
Authors: Della Guardia Lucio , Shin Andrew C.
Published: March 2022

Chronic exposure to high levels of particulate matter (PM) is correlated to a higher prevalence of cardio-metabolic disturbances. Adipose tissue represents a pivotal regulator of metabolic homeostasis, and its dysfunction is associated with health issues in PM-exposed models. This review discusses the adaptive changes of white (WAT) and brown (BAT) adipose tissue in response to fine particulate matter (PM2.5), investigating the underlying pathophysiology. In exposed models, PM2.5 increases oxidative stress and impairs mitochondria functionality and biogenesis in WAT and BAT. Chronic exposure also upregulates the main apoptotic/pro-inflammatory pathways and promotes the infiltration of monocytes and the accumulation of activated macrophages. Oxidative stress and inflammation are responsible for the inhibition of insulin signal transduction and glucose uptake in both the adipose tissues. The increased inflammatory status also suppresses the metabolic activity of brown adipocytes, promoting the whitening. Altogether, this evidence suggests the shift of WAT and BAT toward an inflammatory and metabolic dysfunctional phenotype. Although the underlying mechanisms remain to be clarified, the development of inflammation in lungs, gut, and hypothalamus seems to have a pivotal role in the alteration of adipose tissue homeostasis. The potential consequences on systemic cardio-metabolic health render the relationship PM-adipose tissue a key issue to investigate.

Graphical abstract
Fluorescence-coupled micropipette aspiration assay to examine calcium mobilization caused by red blood cell mechanosensing
Authors: Wang Haoqing , Obeidy Peyman , Wang Zihao , Zhao Yunduo , Wang Yao , Su Qian Peter , Cox Charles D. , Ju Lining Arnold
Published: March 2022

Mechanical stimuli such as tension, compression, and shear stress play critical roles in the physiological functions of red blood cells (RBCs) and their homeostasis, ATP release, and rheological properties. Intracellular calcium (Ca2+) mobilization reflects RBC mechanosensing as they transverse the complex vasculature. Emerging studies have demonstrated the presence of mechanosensitive Ca2+ permeable ion channels and their function has been implicated in the regulation of RBC volume and deformability. However, how these mechanoreceptors trigger Ca2+ influx and subsequent cellular responses are still unclear. Here, we introduce a fluorescence-coupled micropipette aspiration assay to examine RBC mechanosensing at the single-cell level. To achieve a wide range of cell aspirations, we implemented and compared two negative pressure adjusting apparatuses: a homemade water manometer (− 2.94 to 0 mmH2O) and a pneumatic high-speed pressure clamp (− 25 to 0 mmHg). To visualize Ca2+ influx, RBCs were pre-loaded with an intensiometric probe Cal-520 AM, then imaged under a confocal microscope with concurrent bright-field and fluorescent imaging at acquisition rates of 10 frames per second. Remarkably, we observed the related changes in intracellular Ca2+ levels immediately after aspirating individual RBCs in a pressure-dependent manner. The RBC aspirated by the water manometer only displayed 1.1-fold increase in fluorescence intensity, whereas the RBC aspirated by the pneumatic clamp showed up to threefold increase. These results demonstrated the water manometer as a gentle tool for cell manipulation with minimal pre-activation, while the high-speed pneumatic clamp as a much stronger pressure actuator to examine cell mechanosensing directly. Together, this multimodal platform enables us to precisely control aspiration and membrane tension, and subsequently correlate this with intracellular calcium concentration dynamics in a robust and reproducible manner.
Achievement of Key Performance Indicators in Initial Assessment and Care of Injured Patients in Ghanaian Non‐tertiary Hospitals: An Observational Study
Authors: Gyedu Adam , Quainoo Emmanuel , Nakua Emmanuel , Donkor Peter , Mock Charles
Published: March 2022

Introduction

We aimed to determine the level of achievement of key performance indicators (KPIs) during initial assessment and management of injured persons, as assessed by independent observers, at district and regional hospitals in Ghana.

Methods

Trained observers were stationed at emergency units of six district (first level) and two regional (referral) hospitals, from October 2020 to February 2021, to observe management of injured patients by health service providers. Achievement of KPIs was assessed for all injured patients and for seriously injured patients (admitted for ≥ 24 h, referred, or died).

Results

Management of 1006 injured patients was observed. Road traffic crash was the most common mechanism (63%). Completion of initial triage ranged from 65% for oxygen saturation to 92% for mobility assessment. For primary survey, airway was assessed in 77% of patients, chest examination performed in 66%, and internal abdominal bleeding assessed in 43%. Reassessment rates were low, ranging from 16% for respiratory rate to 23% for level of consciousness. Thirty‐one percent of patients were seriously injured. Completion of KPIs was higher for these patients, but reassessment remained low, ranging from 25% for respiratory rate to 33% for level of consciousness.

Conclusion

KPIs were performed at a high level, but several specific elements should be performed more frequently, such as oxygen saturation and assessment for internal abdominal bleeding. Reassessment needs to be performed more frequently, especially for seriously injured patients. Overall, care for the injured at non‐tertiary hospitals in Ghana could be improved with a more systematic approach.
Stratification of multiple sclerosis patients using unsupervised machine learning: a single-visit MRI-driven approach
Authors: Pontillo Giuseppe , Penna Simone , Cocozza Sirio , Quarantelli Mario , Gravina Michela , Lanzillo Roberta , Marrone Stefano , Costabile Teresa , Inglese Matilde , Morra Vincenzo Brescia , Riccio Daniele , Elefante Andrea , Petracca Maria , Sansone Carlo , Brunetti Arturo
Published: March 2022

Objectives

To stratify patients with multiple sclerosis (pwMS) based on brain MRI-derived volumetric features using unsupervised machine learning.

Methods

The 3-T brain MRIs of relapsing-remitting pwMS including 3D-T1w and FLAIR-T2w sequences were retrospectively collected, along with Expanded Disability Status Scale (EDSS) scores and long-term (10 ± 2 years) clinical outcomes (EDSS, cognition, and progressive course). From the MRIs, volumes of demyelinating lesions and 116 atlas-defined gray matter regions were automatically segmented and expressed as z-scores referenced to external populations. Following feature selection, baseline MRI-derived biomarkers entered the Subtype and Stage Inference (SuStaIn) algorithm, which estimates subgroups characterized by distinct patterns of biomarker evolution and stages within subgroups. The trained model was then applied to longitudinal MRIs. Stability of subtypes and stage change over time were assessed via Krippendorf’s α and multilevel linear regression models, respectively. The prognostic relevance of SuStaIn classification was assessed with ordinal/logistic regression analyses.

Results

We selected 425 pwMS (35.9 ± 9.9 years; F/M: 301/124), corresponding to 1129 MRI scans, along with healthy controls (N = 148; 35.9 ± 13.0 years; F/M: 77/71) and external pwMS (N = 80; 40.4 ± 11.9 years; F/M: 56/24) as reference populations. Based on 11 biomarkers surviving feature selection, two subtypes were identified, designated as “deep gray matter (DGM)-first” subtype (N = 238) and “cortex-first” subtype (N = 187) according to the atrophy pattern. Subtypes were consistent over time (α = 0.806), with significant annual stage increase (b = 0.20; p < 0.001). EDSS was associated with stage and DGM-first subtype (p ≤ 0.02). Baseline stage predicted long-term disability, transition to progressive course, and cognitive impairment (p ≤ 0.03), with the latter also associated with DGM-first subtype (p = 0.005).

Conclusions

Unsupervised learning modelling of brain MRI-derived volumetric features provides a biologically reliable and prognostically meaningful stratification of pwMS.

Key Points

• The unsupervised modelling of brain MRI-derived volumetric features can provide a single-visit stratification of multiple sclerosis patients.

• The so-obtained classification tends to be consistent over time and captures disease-related brain damage progression, supporting the biological reliability of the model.

• Baseline stratification predicts long-term clinical disability, cognition, and transition to secondary progressive course.
Sea level changes mechanisms in the MPI-ESM under FAFMIP forcing conditions
Authors: Zhang Xiaolin , Ojha Sayantani , Köhl Armin , Haak Helmuth , Jungclaus Johann H. , Stammer Detlef
Published: March 2022

Mechanistic causes for sea level (SL) change patterns are analyzed as they emerge from the Coupled Model Intercomparison Project Phase 6 (CMIP6) endorsed Flux-Anomaly-Forced Model Intercomparison Project (FAFMIP) coupled climate experiments imposing individual forcing anomalies in wind stress, heatflux and freshwater flux to the Max-Planck-Institute Earth System Model (MPI-ESM). It appears that the heat flux perturbations have the largest effect on the sea level. In contrast, the direct impact of momentum and freshwater flux anomalies on SL anomalies appear to be limited to some region e.g. the Southern Ocean, Arctic Ocean and to some extent the North Pacific and North Atlantic Ocean. We find that thermosteric changes dominate the total SL change over large parts of the global ocean, except north of 60 °N where halosteric changes prevail. An analysis of added and redistributed components of heat and freshwater further suggests that the added component dominates the thermosteric SL and the redistributed component dominates the halosteric SL. Due to feedback processes a superposition of all forcing components together leads to the simulated sea level changes in each individual experiment. As a result, large surface heat flux anomalies over the Atlantic lead to wind stress change outside of the Atlantic through teleconnections, which in turn appear to be the primary driving agent for changes of sea level outside of the Atlantic in all three experiments. The associated wind driven Sverdrup stream function implicates that outside of the Atlantic most of the feedback can be explained by changes in the Sverdrup circulation.
A novel bilateral anterior sacrospinous hysteropexy technique for apical pelvic organ prolapse repair via the vaginal route: a cohort study
Authors: Naumann Gert , Börner Clara , Naumann Lena-Johanna , Schröder Sebastian , Hüsch Tanja
Published: March 2022

Background

Uterine-preserving techniques are becoming increasingly popular in the last decade. This investigation evaluates a novel hysteropexy technique using a mesh in sling-alike configuration [Splentis (Promedon, Argentina)] which is attached anteriorly to the cervix and suspended to the sacrospinous ligaments bilaterally via the vaginal route in women undergoing surgery for uterine prolapse.

Methods

This was a single-center cohort study, evaluating women who underwent transvaginal hysteropexy with Splentis for primary uterine descent. Data have been collected prospectively as part of the quality assurance system. Primary endpoint was treatment success, defined as a combined endpoint including the absence of a vaginal bulge symptom and no retreatment of apical prolapse. A validated questionnaire to evaluate quality-of-life and prolapse symptoms was utilized. Descriptive analysis was applied. Wilcoxon signed-rank test was performed to compare paired samples. The significance level was set at 5%.

Results

A total of 103 women with a median age of 68.0 [IQR 11.5] years with a median apical POP-Q stage of 3 were included. The median surgery time was 22 [IQR 12] minutes and no intraoperative complication occurred. After a median follow-up time of 17 months, treatment success was achieved in 91 (89.2%) patients and quality of life and patient report outcomes improved significantly (p < 0.001). Mesh exposure occurred in 3 (2.9%) patients. Of these, two patients required surgical revision, and one patient was treated conservatively. One patient required partial mesh removal due to dyspareunia.

Conclusion

Bilateral sacrospinous hysteropexy with Splentis offers an efficacious and safe alternative for apical compartment repair, incorporating the advantages of pelvic floor reconstruction via the vaginal route.
Fatal diving: could it be an immersion pulmonary edema? Case report
Authors: Evain France , Louge Pierre , Pignel Rodrigue , Fracasso Tony , Rouyer Frédéric
Published: March 2022

Immersion pulmonary edema is a rare, underrecognized, and potentially lethal pathology developing during scuba diving and other immersion-related activities (swimming or apnoea). Physiopathology is complex and not fully understood, but its mechanisms involve an alteration of the alveolo-capillary barrier caused by transcapillary pressure elevation during immersion, leading to an accumulation of fluid and blood in the alveolar space. Diagnosis remains a challenge for clinicians and forensic practionner. The symptoms begin during ascent, with cough, frothy sputum, and hemoptysis. Auscultation reveals signs of pulmonary edema. Pulmonary CT scan, which is the radiological exam of choice, shows ground glass opacities and interlobular thickening, eventually demonstrating a patterned distribution, likely in the anterior segments of both lungs. Apart from the support of vital functions, there is no specific treatment and hyperbaric oxygen therapy is not systematically recommended. We present a case of fatal IPE occurring in a recreational diver who unfortunately died shortly after his last dive. Diagnosis was made after complete forensic investigations including post-mortem-computed tomography, complete forensic autopsy, histological examination, and toxicological analysis.
Impact on daily mobility and risk of falling in bilateral vestibulopathy
Authors: Wuehr M. , Decker J. , Schenkel F. , Jahn K. , Schniepp R.
Published: March 2022

Objective

To study the behavioral relevance of postural and ocular-motor deficits on daily activity and risk of falling in patients with bilateral vestibular hypofunction (BVH).

Methods

Thirty patients with BVH and 30 age- and gender-matched healthy controls participated in a continuous 2-week assessment of daily activities and mobility using a body-worn inertial sensor and a 6-month prospective fall risk assessment. At inclusion, patients and controls further underwent a multi-modal clinical, score- and instrument-based assessment of general health and balance status. We analyzed the relationship between clinical, lab-, and sensor-based measures and their validity to identify those patients at a risk of general, frequent, and severe falling.

Results

Patients exhibited impairments in daily activity in particular in terms of reduced ambulatory activity (p = 0.009). 43% of patients experienced falls (13% in controls, p = 0.008) and 70% of these patients reported recurrent falling (0% in controls, p = 0.001) during prospective assessment. Severe fall-related injuries that would require medical attention neither occurred in patients nor in controls. Classificatory models based on multi-modal clinical, lab-, and sensor-based measures of balance and mobility identified patients who fell with an accuracy of 93% and patients who recurrently fell with an accuracy of 89%.

Conclusion

BVH is linked to particular impairments of patients’ daily activities which in turn are related to patients’ fall risk. Hence, off-laboratory measures of daily mobility may supplement standard clinical assessment in BVH to more adequately capture the burden of disease and to reliably identify those patients at a specific risk of falling.
The repetition of errors in recall: a review of four ‘fragmentation’ experiments
Authors: Laming Donald
Published: March 2022

This review reanalyses the data from four experiments originally designed to test the fragmentation hypothesis. Participants were asked to recall triple or quadruple associates, cued by each of their components in turn, and to guess if they could not remember. There were many errors in recall and many of those errors were repetitions of previous errors. This reanalysis focuses, not on the fragmentation hypothesis, but on the repetition of errors. It works backwards through sequences of test trials to discover the best prior match to the responses on each trial. It reports frequencies of different categories of repetition, conditional probabilities of repetition, correct recalls, and the probability of repetition in relation to the lag between trial and match in the test sequence. These results may be summarised as (1) every event (a stimulus or a response or just a retrieval) to which the participant attends is separately recorded in memory, creating an ordered record of those events that have engaged the participant’s attention; (2) the compilation of the record is automatic; while attention to a stimulus is at the participant’s disposal, the consequent entry into memory is not, and (3) the retrieval of a potential response from memory is spontaneous; that retrieval becomes an overt response if it is compatible with the cue. This makes sense of a number of historic anomalies in the study of recall and informs some contemporary problems in the study of short-term memory.
Structural connectivity in ventral language pathways characterizes non-verbal autism
Authors: Olivé Guillem , Slušná Dominika , Vaquero Lucía , Muchart-López Jordi , Rodríguez-Fornells Antoni , Hinzen Wolfram
Published: March 2022

Language capacities in autism spectrum disorders (ASD) range from normal scores on standardized language tests to absence of functional language in a substantial minority of 30% of individuals with ASD. Due to practical difficulties of scanning at this severe end of the spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the first time, the integrity of the core white matter tracts defining the language connectivity network in non-verbal ASD (nvASD): the three segments of the arcuate (AF), the inferior fronto-occipital (IFOF), the inferior longitudinal (ILF) and the uncinate (UF) fasciculi, and the frontal aslant tract (FAT). A multiple case series of nine individuals with nvASD were compared to matched individuals with verbal ASD (vASD) and typical development (TD). Bonferroni-corrected repeated measure ANOVAs were performed separately for each tract—Hemisphere (2:Left/Right) × Group (3:TD/vASD/nvASD). Main results revealed (i) a main effect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a main effect of group revealing lower values of radial diffusivity (RD) in the long segment of the AF in nvASD compared to vASD group; and (iii) a reduced volume in the left hemisphere of the UF when compared to the right, in the vASD group only. These results do not replicate volumetric differences of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, in line with semantic deficits observed behaviourally in this group.
Chronischer Schmerz als existenzielle Herausforderung
Authors: Kieselbach Kristin , Koesling Dominik , Wabel Thomas , Frede Ursula , Bozzaro Claudia
Published: March 2022

Das biopsychosoziale Schmerzkonzept stellt gegenwärtig den Schwerpunkt schmerztherapeutischer Behandlungsprogramme dar. Jedoch kann damit die Komplexität chronischer Schmerzen, insbesondere ihre Bedeutung für die Betroffenen, nur unzureichend erfasst werden. Denn ein Kernaspekt des Phänomens chronischer Schmerz wird bislang nur in Einzelfällen berücksichtigt: sein existenzieller Charakter. Chronische Schmerzen können das Selbst- und Weltverständnis, die Lebenswünsche und -ziele, letztlich die gesamte Integrität der Betroffenen bedrohen. Selbstaussagen Erkrankter zeigen, dass chronischer Schmerz immer ein existenzielles Widerfahrnis darstellt und den Menschen in seiner Gesamtheit erfasst. Dies wird durch zwei Aspekte deutlich: zum einen durch die existenzielle Verzweiflung am Schmerz, zum anderen durch Fragen der Sinngebung und Neuorientierung. Allerdings berücksichtigen gängige Therapiekonzepte den existenziellen Charakter mit derartigen Herausforderungen bislang nicht adäquat. Chronischer Schmerz sollte daher stets unter einer umfassenden Perspektive wahrgenommen und behandelt werden. Hierbei sind die Aspekte Einzigartigkeit anerkennen, zum Ausdruck verhelfen und dem Er-leben Raum geben zur Unterstützung Erkrankter in ihrer Auseinandersetzung mit dem Schmerz besonders zu berücksichtigen.
Effectiveness of laminectomy with fusion and laminectomy alone in degenerative cervical myelopathy
Authors: Revesz David Fröjd , Charalampidis Anastasios , Gerdhem Paul
Published: March 2022

Purpose

The effectiveness of laminectomy with fusion and laminectomy alone in degenerative cervical myelopathy was compared.

Methods

Individuals treated with laminectomy with fusion or laminectomy alone at or below the second cervical vertebra were identified in the Swedish spine registry. 66 individuals treated with laminectomy and instrumented fusion were age matched to 132 individuals treated with laminectomy alone. The European Myelopathy Scale (EMS), the Neck Disability Index (NDI), the Numeric Rating Scale (NRS) for neck pain and the EQ-5D index were available at baseline, and at 1 and 2 year follow-ups. Statistical analyses were performed with Mann–Whitney U tests and paired T tests. Effect sizes were described with Cohen’s D.

Results

Data at baseline did not differ significantly between the groups with the exception of a longer laminectomy in the fusion group (4.2 vs 3.4 vertebras; p < 0.001). Both groups improved EMS, NDI, NRS and EQ-5D from baseline to 1 year (p ≤ 0.011), with no additional improvement between 1 and 2 years (all p ≥ 0.09). Effect sizes for change from baseline were small to medium in both groups. At 2 years the laminectomy with fusion group and the laminectomy alone group had a median (25th;75th percentile) EMS of 13 (11;13) and 13 (11;15) (p = 0.77), NDI of 39 (24;54) and 27 (10;41) (p = 0.045), NRS of 4 (1;2) and 2 (0;5) (p = 0.048), and EQ-5D index of 0.67 (0.25;0.73) and 0.66 (0.17;0.76) (p = 0.96).

Conclusion

The results of this study suggest similar effectiveness of laminectomy with instrumented fusion and laminectomy alone in degenerative cervical myelopathy.

Level of evidence

III.