bluuebunny/crossref_metadata_2025 huggingface dataset:
The background sodium leak channel NALCN is a major controlling factor in pituitary cell excitability
Authors: Belal Marziyeh , Mucha Mariusz , Monteil Arnaud , Winyard Paul G. , Pawlak Robert , Walker Jamie J. , Tabak Joel , Belle Mino D. C.
Published: December 2024

The pituitary gland produces and secretes a variety of hormones that are essential to life, such as for the regulation of growth and development, metabolism, reproduction, and the stress response. This is achieved through an intricate signalling interplay between the brain and peripheral feedback signals that shape pituitary cell excitability by regulating the ion channel properties of these cells. In addition, endocrine anterior pituitary cells spontaneously fire action potentials to regulate the intracellular calcium ([Ca2+]i) level, an essential signalling conduit for hormonal secretion. To this end, pituitary cells must regulate their resting membrane potential (RMP) close to the firing threshold, but the molecular identity of the ionic mechanisms responsible for this remains largely unknown. Here, we revealed that the sodium leak channel NALCN, known to modulate neuronal excitability elsewhere in the brain, regulates excitability in the mouse anterior endocrine pituitary cells. Using viral transduction combined with powerful electrophysiology methods and calcium imaging, we show that NALCN forms the major Na+ leak conductance in these cells, appropriately tuning cellular RMP for sustaining spontaneous firing activity. Genetic depletion of NALCN channel activity drastically hyperpolarised these cells, suppressing their firing and [Ca2+]i oscillations. Remarkably, despite this profound function of NALCN conductance in controlling pituitary cell excitability, it represents a very small fraction of the total cell conductance. Because NALCN responds to hypothalamic hormones, our results also provide a plausible mechanism through which hormonal feedback signals from the brain and body could powerfully affect pituitary activity to influence hormonal function.

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Key points

Pituitary hormones are essential to life as they regulate important physiological processes, such as growth and development, metabolism, reproduction and the stress response.

Pituitary hormonal secretion relies on the spontaneous electrical activity of pituitary cells and co‐ordinated inputs from the brain and periphery. This appropriately regulates intracellular calcium signals in pituitary cells to trigger hormonal release.

Using viral transduction in combination with electrophysiology and calcium imaging, we show that the activity of the background leak channel NALCN is a major controlling factor in eliciting spontaneous electrical activity and intracellular calcium signalling in pituitary cells.

Remarkably, our results revealed that a minute change in NALCN activity could have a major influence on pituitary cell excitability.

Our study provides a plausible mechanism through which the brain and body could intricately control pituitary activity to influence hormonal function.
Water Quality Assessment Using Overall Index of Pollution (OIP) in Upper Godavari River (Maharashtra, India)
Authors: Salunke Vasudev Shivaji , Zaware Pramila Popatrav
Published: December 2024

This study on water quality assessment in Upper Godavari River basin (India) was conducted for a period of one year between 2018 and 2019. An Overall Index of Pollution (OIP) was applied to assess the water quality to determine the water quality. Water samples were collected for post Monsoon season June to September. Physical and chemical parameters such as pH, electrical conductivity, total dissolved solids, turbidity, dissolved oxygen, biological oxygen demand, sulphate, and chloride were investigated for three selected sites. As a result, the OIP values of different sites explains that water quality of Upper Godavari River basin was observed between ‘slightly polluted’ to ‘polluted’. Therefore, surface water quality of upper Godavari basin within the urbanized area and industrial area had high OIP score, and it required urgent management for the mitigation for the ecological sustainability and protection of aquatic life.
Great Excavations: Methodological considerations arising after a major archaeological infrastructure project for the A14 Cambridge to Huntingdon Road Improvement Scheme
Authors:   Headland Archaeology Ltd, Smith Alex , West Emma ,   Headland Archaeology Ltd, Sherlock Stephen ,   A14 Integrated Delivery Team, Gdaniec Kasia ,   Cambridgeshire Historic Environment Team, Bowsher David ,   MOLA
Published: December 2024

This short paper draws together and evaluates some of the main methodologies utilized within the different stages of the A14 project and provides some 'lessons learned' that may be useful for future archaeological projects, particularly those associated with large infrastructure. To deliver a more balanced methodological evaluation, perspectives from different project stakeholders are captured here: those of the client (National Highways and A14 IDT), principal archaeological contractor (MHI) and curator (Cambridgeshire Historic Environment Team; CHET).
Investigating the Influence of Fueling Strategies and Spark on Combustion Instability for a Single Cylinder Two-Stroke Natural Gas Engine
Authors: Pommier Forrest , Stewart Emma , Patterson Mark , Jacobs Timothy
Published: December 2024

Emissions reductions are the primary driver for technological innovation in the gas compression industry with partial-fire and misfire events contributing significantly to the total output of hydrocarbons. A single misfire event in a large-bore two-stroke engine can be equivalent to over a hundred normal firing cycles. With government regulations continuing to restrict an engine’s allowable emissions, equipment manufacturers and operators are in search of solutions that can effectively and reliably reduce combustion instability, and understanding the root causes is an instrumental step towards that goal. Exploring the numerous possible contributors to combustion instability is a large endeavor, so this paper narrows the scope to studying methods of fueling and effects of spark timing on large-bore two-stroke natural gas engines. This investigation into fueling assesses both carburetion and direct injection fueling strategies at a range of spark timings. The direct injection fueling system is also tested at a series of fuel pressures. Typically, direct fuel injection has shown to lower total hydrocarbon emissions by reducing short-circuiting. However, its impact to an engine’s stability has not been thoroughly investigated for large-bore single cylinder two-stroke engines. Studying these fundamental parameters provides insight into potential contributors of engine instability and understanding how to mitigate them and ultimately reduce emissions.
Operation of a Compression Ignition Engine at Idling Load Under Simulated Cold Weather Conditions
Authors: Dev Shouvik , Guo Hongsheng , Liko Brian , Lafrance Simon
Published: December 2024

Heavy-duty compression ignition (CI) engines can be subject to long periods of idling during their duty cycles. In colder climates, getting the engine and exhaust aftertreatment system (EATS) to ideal operating temperatures can be challenging under such idling and low load conditions. This may lead to high emissions of criteria pollutants especially nitrogen oxides (NOx). Increasing the engine load and idling speed may help mitigate NOx emissions but typically leads to higher greenhouse gas (GHG) emissions. Therefore, the objective of this study is to evaluate the performance of a heavy-duty CI engine operating at various idling conditions and determine suitability for EATS operation.

Tests are conducted on a heavy-duty single cylinder CI research engine fueled with diesel. As per the United States’ (US) Code of Federal Regulations (CFR), CI engines can be certified for the optional Clean Idle NOx emission standard. A corresponding two-mode Clean Idle Test (CIT) is specified in CFR which requires the engine to be operating in fully warmed-up condition at two engine speeds. Steady state tests are conducted at these two engine speeds of 650 and 1100 rpm, and cold weather operation is simulated by operating the engine at sub-optimal coolant, lubricant, and intake air temperatures. The steady state tests are used to determine suitable diesel injection timing for performing the CIT under standard and simulated cold weather conditions.

At the lowest load and 650 rpm idling speed, use of multiple injections and exhaust gas recirculation (EGR) are insufficient for raising the exhaust gas temperature above 200°C. A combination of higher load, EGR, and 1100 rpm idling speed can create conditions for light-off selective catalytic reduction (LO-SCR) operation at the expense of higher fuel consumption. The modified CIT results show that the optional Clean Idle NOx emission standards can be met with the use of EGR at both test modes. The Mode 2 conditions at 1100 rpm may allow LO-SCR activation as well. There are also distinct differences between results under fully and partially warmed-up conditions.
Numerical Investigation on Temperature Dependence of Flame Behavior in High Pressure Direct Injection Combustion of Diesel Piloted Liquid Ammonia Sprays
Authors: Pathak Utkarsh , Scharl Valentin , Krnac Dominik , Sattelmayer Thomas
Published: December 2024

Ammonia is a viable carbon-free alternative to fossil fuels used in large internal combustion engines (ICEs). However, it is characterized by its reluctance to combust due to a high heat of vaporization, low flame speeds and high auto-ignition temperature. High-pressure dual-fuel (HPDF) combustion of ammonia, piloted by diesel, has been shown to overcome these unfavorable combustion characteristics. The stability of ammonia diffusion flame under these conditions determines the overall efficiency of combustion and pollutant formation. Nevertheless, the mechanisms governing ammonia flame behavior in HPDF combustion remain under-examined in the scientific literature. This work investigates the temperature dependence of flame behavior in the combustion of diesel-piloted liquid ammonia sprays using detailed chemistry simulations. A three-dimensional computational fluid dynamics (CFD) model is developed to simulate ammonia spray combustion in a rapid compression expansion machine (RCEM). Simulation results for evaporating and combusting sprays are validated against experimentally obtained optical and heat release rate (HRR) data. Subsequently, numerical investigations are conducted using the validated CFD model to isolate the effect of ambient mixture temperature on ammonia flame stability by varying the temperature while maintaining an operating pressure of 125 bar. The resulting structure of the flame is discussed in depth at several stages of combustion for the relevant temperatures. It is shown that ammonia flame does not stabilize up to a temperature of 1100 K and drifts downstream of the flow. The study reveals the mechanism through which a strong spatial and temporal interaction between ammonia spray and diesel combustion products promotes flame stabilization in the HPDF combustion of ammonia at high temperatures. High ambient mixture temperatures lead to increased NOx formation.
Development of an On-Road Stochiometric Heavy Duty Natural Gas Engine
Authors: Kandappadi Sudheesh , Stetter John , Banerjee Pranay , Kandlagunta Ankababu , Shah Jay , Shipp Timothy , Mohr Daniel
Published: December 2024

As the emission regulations are getting more stringent, engine manufacturers are continuously improving engine performance and emissions along with exploring alternative fuel options. Diesel engines dominate the current on highway heavy duty engine market. Compared with diesel, natural gas engines have many advantages like near zero soot emissions, lower CO2 emissions, lower operating cost, quieter operation, and domestic natural gas availability. Natural engines can operate at stoichiometric air fuel ratio and allow for the use of cost effective three-way catalytic converter to achieve emission targets. Moreover, Renewable Natural Gas (RNG) is the only fuel in the market with carbon negative intensity. To improve the overall engine efficiency, new engine design integrates tumble combustion, dual overhead camshaft, variable valve train system, optimized fuel system, pulse Exhaust Gas Recirculation (EGR) system and optimized turbocharger. Integration and optimization of new technologies has improved the peak Brake Thermal Efficiency (BTE) by 12% above the current Cummins heavy-duty production engine. Average transient cycle BTE is improved by 16% on Ramped Mode Cycle Supplemental Emissions Test (RMCSET) and 17% on Federal Test Procedure (FTP) cycles. Optimized architecture has demonstrated system out emission capability of 0.02 g/hp-hr. on both the FTP and RMCSET cycles.
Emissions, Performance and Vibro-Acoustic Analysis of a Compression-Ignition Engine Running on Hydrotreated Vegetable Oil (HVO)
Authors: Colangeli Claudio , d’Ambrosio Stefano , Mancarella Alessandro , Marello Omar , Salamone Nicolò
Published: December 2024

To meet future energy sustainability and carbon neutrality requirements, disruptive changes to the current energy mix are expected. Renewable fuels, such as hydrotreated vegetable oil (HVO), could play an important role in this context. To assess the potential of HVO, further quantitative research analyses are still required in order to emphasize the benefits (and drawbacks, if any) from a global perspective, rather than limiting the investigation to a single topic (e.g., emissions).

For this purpose, HVO and conventional diesel were compared, in this study, running initially the engine with the same (diesel-oriented) calibration, before being optimized using purposely developed fuel-specific calibrations.

In terms of exhaust pollutant emissions, HVO showed the potential to substantially reduce engine-out emissions of soot, HC and CO at low loads, while differences in exhaust emissions at higher loads proved to be mainly determined by the amount of oxygen available in the combustion chamber, rather than the specific characteristics of the fuels. HVO also demonstrated reductions in tank-to-wheel CO2 emissions, due to lower fuel consumption, even though the primary benefit of renewable fuels should be highlighted in a larger well-to-wheel analysis.

In addition to emission analyses, since extensive investigations on the area of vibroacoustic behavior of engines running on renewable fuels are rare in the literature, a thorough comparison between regular diesel and HVO was carried out on this aspect. In this preliminary activity, the acoustic analysis focused solely on combustion noise, which was extracted by using dedicated signal processing techniques. This approach allowed the authors to focus on the noise contribution that is specifically influenced by the fuel characteristics. Furthermore, the vibrations of the engine block were evaluated. The results showed slightly lower levels of HVO in terms of both noise and vibrations.
Assessment of Performance and Emissions of an RCCI-Diesel Dual Combustion Mode Engine During a Vehicle Duty Cycle
Authors: Khedkar Nikhil , Marwaha Tejasva , Sarangi Asish Kumar , Sreedhara Sheshadri , Singh Arvind Kumar
Published: December 2024

Dual fuel reactivity controlled compression ignition (RCCI) engines are capable of operating on both renewable and conventional fuels. They produce ultra-low nitrogen oxides (NOx) and particulate matter (PM) emissions while maintaining thermal efficiency similar to that of conventional diesel engine operating at part load conditions. However, the engine needs to transition to the conventional diesel combustion (CDC) mode during high speed and high load operation due to the limited operating range of the engine in the RCCI mode. This study aims to compare a virtual vehicle level drive cycle-based fuel economy and emissions data for the RCCI (operating with both gasoline-diesel and compressed natural gas (CNG)-diesel) and CDC dual combustion mode engine. In this work a combination of engine experimental data and a vehicle powertrain simulation tool (AVL CRUISE) is employed to determine the vehicle level emissions and performance of a light-duty commercial vehicle on the world-wide harmonized light-duty test cycle (WLTC). The vehicle duty cycle results demonstrate ∼62% decrease in NOx and ∼36% reduction in soot emissions with the gasoline-diesel RCCI-CDC engine compared to conventional diesel only operation. A further 26% reduction of soot emission is observed with the CNG-diesel RCCI-CDC dual combustion mode engine. However, the combustion efficiency decreased in the RCCI mode resulting in a significant increase in total hydrocarbon (THC) and carbon monoxide (CO) emissions. Despite the poor combustion efficiency and marginally reduced thermal efficiency of the RCCI mode, the fuel economy of the vehicle, with the RCCI-CDC dual combustion mode engine, undergoing the WLTC drive cycle is comparable with the diesel only vehicle. Fuel economy of 21.2 km/l (diesel equivalent) and 21.6 km/l (diesel equivalent) are estimated with the gasoline-diesel and CNG-diesel RCCI-CDC modes, respectively, compared to 22.3 km/l (diesel) of conventional diesel only operation. Engine-out CO2 reduced by 7% in case of gasoline-diesel RCCI-CDC engine whereas, due to the lower carbon to hydrogen ratio in the CNG-diesel RCCI-CDC dual combustion mode engine, engine-out CO2 reduced by 16% as compared to CDC only operation. However, when the global warming potential of methane was considered, the CO2 equivalent emissions for the CNG-diesel RCCI-CDC dual combustion mode engine were 1.67 times higher than that for CDC.
Enhancement of the Ammonia Kinetic Mechanism for Nitrogen-Based Pollutant Chemistry
Authors: Ou Juan , Yan Yuchao , Yang Ruomiao , Liu Zhentao , Liu Jinlong
Published: December 2024

Ammonia is a promising carbon-neutral fuel for internal combustion engines. However, its widespread application requires accurate ammonia kinetic models for numerical simulations used in engine development. Current development of ammonia kinetics mainly focuses on predicting fundamental combustion parameters such as ignition delay and laminar flame speed. Yet, significant discrepancies remain among different kinetics in predicting nitrogen-based pollutants (such as NOx and N2O). To improve the immature ammonia kinetics, especially for nitrogen-based pollutant chemistry, this study applies the Reaction Mechanism Generator (RMG) tool to enhance existing kinetics from the literature. Additionally, the kinetics is further optimized by incorporating advanced theoretical calculations of key reaction rates from the latest literature. The results show that the RMG-derived models excel in predicting species concentrations, ignition delay times, and laminar flame speeds. Moreover, the RMG-improved kinetics significantly enhances model robustness and applicability by automatically generating and expanding chemical reaction networks and iteratively adding new reactions and species that are essential according to the flux analysis. Further, kinetic analysis reveals the presence of an important species, HN2O, missing in the chemical mechanism from existing literature, which shows high sensitivity in the ammonia oxidation pathway. Overall, these findings highlight the need for more fundamental studies to improve immature ammonia oxidation kinetics by identifying new oxidation pathways and key species under a wider range of conditions representative of engine in-cylinder conditions, which is vital for predicting ammonia engine nitrogen-based emissions and finding strategies to control them.
A Study on Factors Affecting Oil Film Thickness on Sliding Surface of Three-Piece Oil Control Ring
Authors: Miura Ken , Kikuhara Koji , Tsukamoto Kazuki , Kumar Ayush , Ito Akemi
Published: December 2024

Oil consumption of an engine causes particulate matter generation, catalyst poisoning in an aftertreatment device, and abnormal combustion such as pre-ignition. Oil control rings (OCRs) play a role of controlling amount of oil on the sliding surface and are important engine components in reducing oil consumption. Since the OCR has the highest ring tensions in the piston ring pack, the OCR is expected to fit into the cylinder bore. However, measurement data of the oil film thickness on the sliding surface of the OCR has shown that the actual oil film was thicker than the theoretical value.

In this study, factors which affect the oil film thickness on the sliding surface of a three-piece oil control ring (TPOCR) were investigated by the direct measurement of the oil film thickness on the sliding surface and the lower flank of the TPOCR. Piston secondary motion in the actual engine was also measured to analyze the effect of lateral and tilting motion of the piston on the oil film thickness. Those effects were also analyzed using a rig tester. Posture of the OCR rails were also considered to analyze oil film thickness data.

It was found that the lateral and the tilting motion of the piston affects the oil film thickness. It was shown that a certain posture of the OCR rail restrained expander movement and also caused a thicker oil film. The bore distortion in the circumferential direction was one of factors. Those findings suggest that piston, OCR motion and bore shape must be considered in the case of calculation of oil film thickness for TPOCR.
Experimental Characterization of Superheated Ammonia Spray From a Single-Hole ECN Spray M Injector
Authors: Bjørgen Karl Oskar , Desclaux Anthony , Mounaïm-Rousselle Christine , Hespel Camille
Published: December 2024

The growing recognition of ammonia as a carbon-free alternative fuel for both transportation and power generation is underscored by numerous studies. While the use of gaseous ammonia injection has been extensively considered, research on the direct injection of liquid ammonia remains relatively scarce, especially in the case of internal combustion engines (ICE). The application of liquid ammonia in gas turbines offers economic and size-related advantages over gaseous ammonia injection. But the liquid ammonia’s instantaneous spray flash-boiling and its high latent heat of vaporization induce the necessity of employing preheated swirling air to enhance flame stability, mitigating the strong cooling effect induced. The preference for direct injection of liquid ammonia is driven by its efficacy in controlling in-cylinder air-fuel ratios and optimizing thermal efficiency. This study presents macroscopic and near-field Schlieren measurements of a 1-hole ECN Spray M, representative of direct liquid injector for engine, with ammonia for different degrees of super-heating. Spray angles and penetration length are provided as a function of the superheat degree with also a focus near the injector nozzle. Additionally, in-spray temperature measurements are presented, providing the first valuable information for modeling purposes.
Demonstrating Diesel Pilot Combustion of Methane-Hydrogen Blends in a Single-Cylinder Compression Ignition Research Engine
Authors: Sirna Amanda , Ristow Hadlich Rodrigo , Loprete Jason , Yamalis Stelios , Trelles Juan Pablo , Van Dam Noah , Mack J. Hunter , Assanis Dimitris
Published: December 2024

Medium and heavy-duty (MHD) diesel engine applications are currently facing technical challenges in accomplishing decarbonization goals due to the lack of readily available technological solutions that can meet the large power density requirements needed. For example, while electrification may show promise for certain light-duty vehicle applications, the benefits are greatly reduced in energy-dense MHD vehicle applications and thus additional decarbonization pathways need to be considered. A promising strategy is the adoption of low/zero carbon fuels that can make use of the abundant number of traditional engine architectures available (and corresponding manufacturing supply chains) to meet both power requirements and decreased emissions requirements. Gaseous fuels of this type include green hydrogen and renewable methane, both of which exhibit characteristics that make them difficult to auto-ignite and combust through increased compression alone. For engines equipped with a direct injector, it is possible to fumigate these engines mainly with gaseous fuel blends in the cylinder head port and use a small volume of renewable diesel directly injected in the combustion chamber (i.e., a pilot injection) to ignite the fumigated gaseous blend mixture. This study builds upon previous work focusing on methane combustion with diesel pilot injection and introduces hydrogen blending, exploring the effects of such fumigated blends at varying start of injection timings and at a constant equivalence ratio. The fuel blend used in this investigation was a diesel pilot injection accounting for ≃2% of the total fuel volume; the other 98% was split between the gaseous fuels, methane and hydrogen, in varying volume blend ratios. The study found that the introduction of any amount of hydrogen reduced carbon dioxide and unburned hydrocarbon concentrations in the exhausted emissions stream when compared to a diesel pilot with pure methane. The presence of hydrogen overall also increased combustion efficiency, peak pressures, and shortened ignition delay time. All blend ratios with hydrogen saw advanced CA50 and shorted CA10 to CA90 duration. This study concluded that tri-fuel blends can be run in a compression ignition engine and a combination of the start of injection timings and volume fraction of hydrogen can be used to control efficiencies and emissions.
Psychological interventions for weight reduction and sustained weight reduction in adults with overweight and obesity: a scoping review
Authors: Hamer Oliver , Kuroski Jennifer A , Bray Emma P , Harris Cath , Blundell Amy , Schneider Emma , Watkins Caroline
Published: December 2024

Introduction

Overweight and obesity are growing public health problems worldwide. Both diet and physical activity have been the primary interventions for weight reduction over the past decade. With increasing rates of overweight and obesity, it is evident that a primary focus on diet and exercise has not resulted in sustained obesity reduction within the global population. There is now a case to explore other weight management strategies such as psychological therapies. However, there is a dearth of literature that has mapped the types of psychological interventions and the characteristics of these interventions as a means of achieving weight reduction.

Objectives

The key objectives focused on mapping the types and characteristics of psychological interventions versus usual care for weight reduction and sustained weight reduction in adults with overweight or obesity. The study followed the scoping review methodology by Arksey and O’Malley and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Eligibility criteria

Intervention studies were included if participants were 18 years and over, classified as overweight or obese (body mass index ≥25 kg/m2) and had received a psychological therapy intervention. Studies were excluded if they included a comparison with other active lifestyle interventions (unless classified as usual care), were not available in English, were not full-text articles or were non-peer-reviewed articles.

Sources of evidence

Six electronic databases were searched from inception to April 2023 to identify relevant articles.

Charting methods

The study employed a systematic charting method and narrative synthesis to organise and synthesise the data.

Results

A total of 31 studies met the eligibility criteria and were included in the review. 13 unique psychological interventions for weight reduction in adults with overweight or obesity were identified, with cognitive–behavioural therapy and motivational interviewing being the most common. Eight types of usual care were identified, which largely included education and training on nutrition and physical activity. Gaps in the current research were also identified.

Conclusion

The findings highlighted several gaps within the existing literature, largely due to a lack of evidence relating to adults with low socioeconomic status, non-white participants, individuals under 40 years of age and the integration of digital health technologies.
Phase I/II trial of intracerebral transplantation of autologous bone marrow stem cells combined with recombinant peptide scaffold for patients with chronic intracerebral haemorrhage: a study protocol
Authors: Kawabori Masahito , Shichinohe Hideo , Kahata Kaoru , Miura Arisa , Maeda Kenichiro , Ito Yoichi M , Mukaino Masahiko , Kogawa Ryo , Nakamura Kentaro , Gotoh Shuho , Kurisu Kota , Fujimura Miki
Published: December 2024

Introduction

Intracerebral haemorrhage (ICH) stands as a leading global cause of death and disability, posing a significant challenge with limited treatment options, especially for chronic patients. Recent advances in stem cell therapies have opened new avenues for therapeutic potential. Our previous preclinical research has demonstrated that intracerebral transplantation of bone marrow stromal cells (BMSCs) combined with a recombinant human collagen type I scaffold enables higher cell survival and engraftment and holds promising potential. In this article, we present the protocol for a novel clinical trial, named ‘Research on Advanced Intervention using Novel Bone MarrOW stem cells for chronic intracerebral haemorrhage’ (RAINBOW-Hx).

Methods and analysis

RAINBOW-Hx is a phase I/II, open-label, uncontrolled study with the primary objective of assessing the safety and efficacy of intracerebral transplantation of autologous BMSCs combined with the scaffold (HUFF-01) in patients with chronic ICH. Eight patients, experiencing moderate to severe neurological deficits for 12 months or longer, will be enrolled. The haemorrhage location will be limited to the basal ganglia and thalamus. Approximately 50 mL of bone marrow will be extracted from the iliac bone of each patient, and BMSCs will be cultured using autologous platelet lysate. 3 days before transplantation, BMSCs will be combined with the scaffold to generate HUFF-01. Each patient will receive a 50 000 HUFF-01 dose, containing approximately 50 million BMSCs, through stereotactic transplantation into the haemorrhagic cavity. Neurological assessments, MRI,18F-fluorodeoxyglucose positron emission tomography and123I-Iomazenil single-photon emission CT will be performed for 1 year after administration.

Ethics and dissemination

The trial protocols were reviewed and approved by the Institutional Review Board of the Hokkaido University Hospital (R5-11), and this study is conducted according to Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The results of this trial will be submitted for publication in a peer-reviewed scientific journal.

Trial registration number

jRCT2013230053, Japan Registry of Clinical Trials.
Defining within-host SARS-CoV-2 RNA viral load kinetics during acute COVID-19 infection within different respiratory compartments and their respective associations with host infectiousness: a protocol for a systematic review and meta-analysis
Authors: Pan Daniel , Martin Christopher A , Nazareth Joshua , Sze Shirley , Al-Oraibi Amani , Gogoi Mayuri , Grolmusova Natalia , Divall Pip , Decker Jonathan , Fletcher Eve , Williams Caroline , Hay James , Baggaley Rebecca F. , Wyllie Anne L , Stephenson Iain , Gaillard Erol , Nellums Laura B , Clark Tristan William , Van-Tam Jonathan Nguyen , Cowling Benjamin J , Hollingsworth T. Déirdre , Gray Laura , Barer Michael , Pareek Manish
Published: December 2024

Introduction

Understanding how RNA viral load changes (viral load kinetics) during acute infection in SARS-CoV-2 can help to identify when and which patients are most infectious. We seek to summarise existing data on the longitudinal RNA viral load kinetics of SARS-CoV-2 sampled from different parts of the respiratory tract (nose, nasopharynx, oropharynx, saliva and exhaled breath) and how this may vary with age, sex, ethnicity, immune status, disease severity, vaccination, treatment and virus variant.

Methods and analysis

We will conduct a systematic review and meta-analysis, using studies identified through MEDLINE and EMBASE (via Ovid). All research studies reporting primary data on longitudinal RNA viral load kinetics of infected patients with SARS-CoV-2 will be included. Methodological quality will be assessed using a validated checklist for longitudinal studies as well as predefined quality criteria for assessment of individual-level RNA viral load. Should the data allow, we will aim to perform individual patient-level meta-analysis. Our primary outcomes are duration to, and quantity of peak RNA viral load, and total duration of viral load shedding within different respiratory compartments. Secondary outcomes include duration of lateral flow antigen and virus culture positivity and variation of RNA viral load by age, immune status, disease severity, vaccination, treatment, lateral flow tests, viral culture positivity and SARS-CoV-2 variant. Study-level effects affecting observations, but not related to properties of the patient, such as the PCR platform and gene target will also be recorded. Random-effects models will estimate the population mean and individual-level variation in viral shedding conditional on the aforementioned variables. Finally, we will summarise the key mechanistic models used in the literature to reconstruct individual-level viral kinetics and estimate how different factors shape viral dynamics over time.

Ethics and dissemination

Ethical approval is not needed as data will be obtained from published articles or studies with data that have already received and ethical review for analysis. Manuscript(s) will be prepared for publication.

Systematic review protocol registration

PROSPERO ID: CRD42023385315
Assessing the characteristics of suicidal ideation and self-harm in a national older adult population attending emergency departments across Ireland: cohort study protocol
Authors: Hoare Fiona , O'Donoghue Ann , Sweeney Colm , McCarthy Geraldine , Kavalidou Katerina , Russell Vincent , Norton Michael John , Doherty Anne M
Published: December 2024

Introduction

Older people (people aged 65 years and older) have high rates of death by suicide, and self-harm is a major risk factor for suicide. While rates of self-harm decrease with age, rates of suicide increase among this age group. The overall aim of this research project is to identify real-life evidence of the characteristics associated with older people who present with self-harm and suicidal ideation to emergency departments in Ireland. In examining the variables associated with self-harm, we may be better able to identify the characteristics of older adults who are at highest risk, including those presenting with high lethality attempts.

Methods and analysis

Our data are a cohort study of older people in Ireland involving two workstreams. The first will use a 5-year cohort of data from the National Clinical Programme for Self-Harm and Suicide-related Ideation (NCPSHI) which comprises over 70 000 presentations. The second workstream will use a 15-year cohort of electronic patient records from the Mater Misericordiae University Hospital (MMUH) comprising over 30 491 presentations (900 aged 65 years and older) to collect more detailed information on characteristics of older people presenting with self-harm and suicidal ideation.

Ethics and dissemination

This study has received full ethical approval. The Clinical Research Ethics Committee of the MMUH approved the MMUH workstream—Reference number: 1/378/2327 TMR. Ethical approval for the NCPSHI workstream has been granted by the University College Dublin’s Office of Research Ethics.

Our findings will be disseminated via peer-review publications and presentations to the scientific community, along with reports for clinicians and policymakers.
SPOON: an observational, cross-sectional study of perceptions and expectations of adults with generalised myasthenia gravis in France
Authors: Camdessanché Jean-Philippe , Sacconi Sabrina , Archer Annie , Boulanger Pierre , Crochard Anne , Bertocchio Jean-Philippe , Richard Aliénor , Villy Pierre-Edouard , Solé Guilhem
Published: December 2024

Objectives

To capture patient perceptions about living with myasthenia gravis (MG) with respect to aspirations and ways to improve treatment.

Design

Online patient survey.

Setting

Patients recruited by MG patient associations or at MG reference treatment centres.

Participants

Adults with physician-diagnosed generalised MG, living in France for ≥12 months, who had received ≥1 MG treatment were eligible. 291 patients opened the questionnaire, 255 were eligible and 246 completed the survey (age range 41–67 years; 187 women and 59 men).

Primary and secondary outcome measures

Primary: free-text response to the question ‘Living with your disease, what would you like to do that you currently find difficult or impossible to do?’ Secondary: free-text response to the question ‘What improvements do you think could be made to treatments for MG?’ Themes from replies to these questions were analysed using grounded theory and cluster analysis.

Results

For the disease aspirations question, 617 citations were provided by 238 participants, which were grouped into 45 dimensions and six high-level domains (physical activity, activities of daily living, psychological burden, social activities, work/school and other). The most frequently cited dimensions were sport (82 citations), greater mobility (56 citations), being less tired (46 citations) and greater endurance (37 citations). Younger age, female gender, recent diagnosis and poorer quality of life were associated with citing more themes. For the treatment amelioration question, 263 citations were provided by 195 participants, which were grouped into 60 dimensions and three high-level domains (medication characteristics, safety and care paradigm). The most cited treatment-related dimensions were fewer side effects (40 citations), fewer daily medication intakes (21 citations) and fewer digestive side effects (20 citations).

Conclusions

These findings could help healthcare professionals to understand and better address patients’ aspirations about living with MG, notably concerning the importance of physical activity, and their expectations for improved treatments.
Irish Prostate Cancer Outcomes Research (IPCOR) registry: cohort profile
Authors: Gordon Noa , Dooley Cara , Murphy Áine , Farooq Wasfa , Sullivan Frank , McDermott Ray , Sharp Linda , Watson William , Galvin David
Published: December 2024

Purpose

To describe the Irish Prostate Cancer Outcomes Research (IPCOR) registry. The cohort was collected to inform and improve the prostate cancer journey of men in Ireland.

Participants

Established in 2015, IPCOR was a unique large-scale prospective cohort study registering men with prostate cancer in Ireland. From 2016 to 2020, IPCOR collected data on 6816 men who were newly diagnosed with prostate cancer across 16 hospitals, both public and private. A comprehensive clinical dataset was collected, capturing detailed information on men’s diagnosis, treatments and follow-up. In addition, a subset of 873 men completed patient-reported outcome measures.

Findings to date

The IPCOR study has revealed several key insights into prostate cancer diagnosis and treatment in Ireland. The data indicate a high rate of diagnosis through opportunistic Prostate-Specific Antigen screening, with many cases identified at an early stage.

Future plans

IPCOR invites collaboration from the global cancer research community to use this resource to advance prostate cancer research and improve patient outcomes worldwide. IPCOR aims to continue updating long-term survival follow-up data for this cohort. It also plans to continue its collaborative approach with patients, engaging with the Lived Experience Advisory Panel in interpreting results emerging from this dataset. Moving forward, IPCOR is planning its next phase of the project, IPCOR 2.0. This will be a prospective, longitudinal, multi-centre clinical quality registry and biorepository.
ArtStory Beats: Highlighting Interactions between Visual Arts and Music with Storytelling
Authors: Vayanou Maria , Katifori Akrivi , Antoniou Angeliki , Loumos George , Ioannidis Yannis
Published: December 2024

In this article, we present the use-case of ArtStory Beats, a mobile application that aims to reflect the creative dialogue between visual arts and music, offering stories about the vibrant interactions that take place within the artistic communities over time. The app use is quite simple: It scans physical copies of visual artworks and provides audio-enhanced stories. However, the audio is not intended to be background or supplementary informative material. It is a music song that somehow relates to the visual artwork, and the stories tell you how. First, we describe our content creation process along with the design of the mobile application. Then we present the results from a qualitative user study with 15 participants, investigating the role and effects of music over several dimensions: overall experience, user satisfaction, and most notably, cultural engagement. The outcomes of the study reveal the potential of the approach to foster curiosity, capture the user’s attention, and support a deeper, reflective connection of the user with the combined artworks. Finally, we discuss the potential use of ArtStory Beats in different contexts, as a remote but also onsite experience, elaborating on related challenges and future directions.
DF-BETA: An FPGA-based Memory Locality Aware Decision Forest Accelerator via Bit-Level Early Termination
Authors: Tokuda Daichi , Takamaeda-Yamazaki Shinya
Published: December 2024

Decision forests, particularly Gradient Boosted Decision Trees (GBDT), are popular due to their high prediction performance and computational efficiency, making them suitable for embedded systems with circuit size and available energy constraints. In this study, we propose a new lightweight GBDT inference acceleration mechanism through the hardware and algorithm co-design. First, we present LoADPack, a hardware-friendly GBDT algorithm that enhances memory access locality. LoADPack obtains trees where the features and thresholds used across the entire ensemble are regular regardless of a branching direction by unifying some nodes and aligning the memory access patterns. Furthermore, we present DF-BETA, a resource-efficient accelerator for the LoADPack algorithm. DF-BETA utilizes MSB-first bit-serial computation to enable early determination of comparison calculations of 32-bit floating-point numbers, optimizing the operation for determining a branch direction. The hardware complexity and computation termination speed vary with the granularity of bit-serial computation. Therefore, we conduct design space exploration of DF-BETA to identify the optimal configuration. Our findings reveal that using 4-bit-serial comparators minimizes circuit size while achieving the leading throughput. Compared to running unconstrained GBDT on a typical accelerator with 32-bit bit-parallel comparators, our accelerator achieves 1.6 times higher throughput on average while maintaining comparable accuracy.
ADEPT 2023 Workshop Summary
Authors: Tran Hai Nam , Singhoff Frank , Hugues Jérôme , Dissaux Pierre , Lewis Bruce , Shackleton Hazel , Kiniry Joseph , Zeyda Frank , Mittal Rakshit , Blouin Dominique , Bhobe Anish , Pautet Laurent , Bae Kyungmin , Ölveczky Peter Csaba , Larson Brian R , Ahmad Ehsan , Kosmidis Leonidas , Valente Hugo , A de Miguel Miguel , Pérez Ángel G , Alonso Alejandro , Zamorano Juan , A de la Puente Juan
Published: December 2024

The Architecture Analysis and Design Language (AADL) is a SAE standard for modeling both hardware and software architecture of embedded systems. Widely embraced by stakeholders in critical real-time embedded systems, the AADL standard is used to address a large set of concerns including performances (latency, schedulability), safety, and security. The ADEPT workshop aims to present and report on current projects in the field of design, implementation, and verification of critical real-time embedded systems where AADL is a first-citizen technology. This article is a summary of the second edition of the workshop in 2023.
BLESS Behavior Correctness Proof as Convincing Verification Artifact
Authors: Larson Brian R. , Ahmad Ehsan
Published: December 2024

Safety-critical cyber-physical systems require evidence they are indeed safe. In practice, such evidence is results of system tests. Unfortunately, tests can only demonstrate the presence of software errors, not their absence, and can practically cover a tiny fraction of system state space. Valiant efforts to formally verify program correctness have either been excruciatingly difficult (theorem proving) or incomplete (static analysis, model checking, SAT or SMT solving).

The BLESS Methodology was created specifically for engineers in industry to formally verify software controlling machines. The BLESS Methodology transforms programs that control machines, annotated with assertions to form proof outlines, into deductive proofs that every possible program execution will conform to its specification. To the extent that cyber-physical system specifications have been validated to express system safety and performance, a deductive proof can be a convincing argument to a person of program correctness.

This paper uses a simple safety-critical system to argue that behavior correctness proof under the BLESS Methodology is a convincing verification artifact in addition to customary testing.
Extension of the TASTE toolset to support publisher-subscriber communication
Authors: Valente Hugo , A de Miguel Miguel , Pérez Ángel G , Alonso Alejandro , Zamorano Juan , A de la Puente uan
Published: December 2024

New Space has been revolutionizing how space software is developed. While in the past the development of systems lasted years to minimize errors, nowadays, with the reduction in manufacturing costs of micro and nanosatellites, companies are capitalizing by focusing on launching frequently, focusing on rapid iterations and innovations. As a result, software development of space systems is also adapting to meet the demands from platform specific code to code that can be reused across different platforms. As a result, there has been a shift from developing tightly coupled client-server systems to loosely coupled publisher subscriber systems.

In this article, we propose a solution focused on integrating cFS, a Publisher Subscriber runtime made by NASA, inside TASTE, a model-based toolset developed by ESA, to build space systems focusing on a publishersubscriber methodology, allowing the user to develop platform agnostic components, allowing for faster iterations, reducing the development time and increasing portability and reusability.
Facilitating AADL Model Processing and Analysis with OSATE-DIM
Authors: Mittal Rakshit , Blouin Dominique
Published: December 2024

The Architecture Analysis and Design Language (AADL) is a rich component-based language for modelling embedded systems. To ease processing AADL models, OSATE, the reference tool for AADL, provides the 'instance' model derived from base 'declarative' model/s. An instance model represents the operational view of a declarative model in a simple object tree where information is flattened (with no component extensions / refinements) so that tools can easily analyze the model. Note that information is lost in instantiation. Since the instance model is a (un-symmetric) 'view' of the declarative model, the capability to directly modify the instance model requires a solution to the view-update problem. We demonstrate the OSATE Declarative-Instance Mapping Tool (OSATEDIM) to perform incremental deinstantiation in AADL. OSATE-DIM significantly eases the development of AADL model processing tools for analysis and code generation.