Severe Limitations Research Articles

Volatilome: A Novel Tool for Risk Scoring in Ischemic Heart Disease.

Developing a novel risk score for accurate assessment of cardiovascular disease (CVD) morbidity and mortality is an urgent need in terms of early prevention and diagnosis and, thereafter, management, particularly of ischemic heart disease. The currently used scores for the evaluation of cardiovascular disease based on the classical risk factors suffer from severe limitations, including inaccurate predictive values. Therefore, we suggest adding a novel non-classical risk factor, including the level of specific exhaled volatile organic compounds that are associated with ischemic heart disease, to the SCORE2 and SCORE2-OP algorithms. Adding these nonclassical risk factors can be used together with the classical risk factors (gender, smoking, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, arterial hypertension, ethnicity, etc.) to develop a new algorithm and further program to be used widely.

The health of older caregivers in Spain: a matter of age or a matter of care?

Abstract Introduction Informal care is crucial in Spain’s care system, with a rising number of caregivers aged 75 or older, yet studies on its health effects are lacking. This study aims to determine the differential impact of age and care-related variables on the health of older caregivers. Materials and methods This is a cross-sectional, national study with a sample of 3,870 informal caregivers from the Spanish 2020 Disability, Personal Autonomy and Dependency Survey. We performed a logistic regression where self-reported deterioration in caregiver health due to caregiving was the dependent variable and age (<75 vs. ≥ 75) was the independent variable. Caregivers’ sex, educational level (primary and lower or secondary and higher), income (<1,150 euros per month vs. ≥ 1,150), severe functional limitation of caregivers and care-receptors (yes or no), duration of care (< 8 years vs. ≥ 8 years), and daily hours of care were used as covariates. Results One in 6 caregivers was 75 or older (16,1%). Caregivers’ mean age was 58.4, and care-receptors’ 66.6 years. Women represented 63.0% of caregivers, and 42.8% of care-receptors. Up to 4.6% of caregivers had a severe limitation, and 43.7% of caregivers reported deterioration of their health due to caregiving. A greater perception of deterioration in caregiver health due to caregiving was associated with being 75 years or older (β = 0.34, p = 0.009). Covariates associated with caregivers’ health deterioration were being a woman (β = 0.77, p < 0.001), presence of severe limitation of care receptors (β = 0.58, p < 0.001), and increased daily hours of care (β = 0.01, p = 0.013). Caregivers’ severe limitation, level of education, income and years of care did not show a significant association with perception of health deterioration. Discussion Caregivers older than 75 years in Spain experience a key deterioration in their health associated with caregiving. This vulnerable population must be prioritized in health and social policies. Key messages • One out of 6 caregivers in Spain is aged 75 years or older. Caregiving impacts greatly in their health status. • Older caregivers is a vulnerable population that must be a priority for health and social services.

Living alone and care levels’ distribution in first-time recipients of long-term care in Germany

Abstract Background As demographic shifts occur, along with longer life expectancies and advancements in medical care, there is a noticeable rise in the population requiring long-term care. In Germany, the Medical Service oversees the assessment for long-term care needs, which specifically evaluates the extent of limitations in maintaining independent living. These limitations are categorized into care levels ranging from 1 (indicating minor limitations) to 5 (denoting the most severe limitations). Methods Data from the long-term care assessment conducted nationwide in Germany are utilized for the analysis presented. The study focuses on individuals aged 60 and above with a first-time recognition of need of long-term care. Descriptive analysis is conducted on the distribution of care levels and living arrangements. Results The analysis encompassed 339,486 individuals, with an average age of 79.6 years (standard deviation: 8.4), of whom 59.0% were female. Approximately half of the sample were categorized under care level 2, while 32.4% fell into care level 1. Higher care levels (3-5) were less frequent (16.2%, 4.8%, 1.7% respectively). Individuals living alone were predominantly found in the lower care levels, whereas those not living alone were more commonly represented in care levels 3-5. Additionally, older individuals were more frequently assigned higher care levels. Conclusions Over 75% of initial applicants are classified within the lowest care levels (1 and 2) with a higher proportion of those living alone. One possible explanation is that within partnerships, the presence of a partner may serve as a form of support during the early phases of long-term care, with external assistance becoming necessary only as care needs escalate to higher levels. Further research should focus on examining the role of living alone in the need for long-term care. Key messages • Initial applicants of long-term care in Germany living alone are more often classified in lower care levels (indicating minor limitations) than in higher care levels (indicating severe limitation). • Partnerships may delay higher long-term care needs; research should explore living alone’s impact on long-term care.

Health literacy & somatic education: a salutogenic self-resource critical health intervention

Abstract Issue Non-communicable diseases (NCDs), such as musculoskeletal conditions, cause severe functional limitations. Therapeutic practices in this field have employed a theoretical-practical framework with a pathogenic and mechanistic bias. However, the causes of these NCD’s are also related to biopsychosocial factors. Therefore, a critical theoretical-practical approach, such as Somatic Education, becomes relevant as it introduces a subjective experience to an educational praxis, modifying the meaning processes in human movement experience in a complimentary approach to the pathogenic perspective. Description of the problem There is a perceptual poverty in movement experience, which dissociates doing from feeling. Somatic practices aim to foster movement awareness (perception) and autonomy (self-regulation), placing the individual as a valuable resource, strengthening the capacity for understanding, reflection and habitus change. This presentation will focus on the following research questions: Can Somatic Education, as a critical intervention of the body, contribute to increased levels of health literacy? Can somatic practices contribute to sustainable health development? Is it possible to create a new meaningful process in human movement experience through this practice incrementing its salutogenic emphasis? Results/Effects Somatic practices foster integrative approaches of health, promoting subjective bodily experience (interface between doing, thinking and feeling). Integrative progress can urge the embodiment of health literacy, encouraging more active and awareness of individuals related to their well-being, contributing to sustainable health development. Moreover, subjective bodily experience transforms the process of meaning in movement experience. Lessons Somatic practices enhance NCDs prevention and education, increasing health literacy rates through innovative conceptual foundations.

O2 consumption overshoot in patients with heart failure: crossing the line

Abstract Background Cardiopulmonary exercise testing (CPET) is among the most valuable clinical tools for evaluating disease severity and physical activity limitations in heart failure (HF) patients. Peak oxygen uptake (pVO2) reflects maximal cardiac output during exercise, and it is considered a major parameter in selecting candidates for cardiac transplantation. VO2 overshoot, a transient increase in VO2 during recovery from maximal exercise, has been frequently observed in HF patients and is attributed to the transient increase in cardiac output caused by the mismatch between cardiac contractility and afterload reduction. However, the prognostic significance of this phenomenon remains to be fully established. Purpose This study aimed to characterize the prognostic significance of VO2 overshoot following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF, with left ventricular ejection fraction (LVEF) <50%, who underwent CPET between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sitting passively for 2 minutes). VO2 overshoot kinetics during recovery were measured and described as the time until post-exercise VO2 fell below pVO2 for at least 15 seconds. Please refer to Figure 1A for an example of normal and prolonged VO2 overshoot. The study endpoint was time to cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) over 1-year follow-up. Results A total of 254 patients were included (mean age 59 ± 12 years; 83% males; mean LVEF 34 ± 9%; 70% with ischemic HF; 77% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean predicted pVO2% 52 ± 16%; mean VE/VCO2 slope 41 ± 13). The VO2 overshoot had a normal distribution (Figure 1B) and lasted on average for 45 ± 33 seconds. There were no differences between patients that had an overshoot higher and below average. Overall, during follow-up, 25 patients met the composite endpoint (12 CV deaths, 9 urgent heart transplants, and 4 LVAD). Univariate analysis showed a significant relationship between VO2 overshoot and the outcome of interest (HR 1.01, 95% CI 1.00 – 1.02, p=0.027). In multivariate analysis, this association remained significant, even after adjusting for pVO2 and VE/VCO2 slope (HR 1.01, CI 95% 1.00– 1.02, p=0.026). Conclusion This study delves into the intriguing phenomenon of VO2 overshoot in patients with heart failure, shedding light on its potential prognostic significance. The independent association between VO2 overshoot and the composite endpoint suggests that this transient increase in oxygen consumption may carry prognostic value. Further studies should confirm these findings.

Multilevel analysis of the central-peripheral-target organ pathway: contributing to recovery after peripheral nerve injury.

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities. Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites, neglecting multilevel pathological analysis of the overall nervous system and target organs. This has led to restrictions on current therapeutic approaches. In this paper, we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective, covering the central nervous system, peripheral nervous system, and target organs. After peripheral nerve injury, the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves; changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord. The nerve will undergo axonal regeneration, activation of Schwann cells, inflammatory response, and vascular system regeneration at the injury site. Corresponding damage to target organs can occur, including skeletal muscle atrophy and sensory receptor disruption. We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury. The main current treatments are conducted passively and include physical factor rehabilitation, pharmacological treatments, cell-based therapies, and physical exercise. However, most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway. Therefore, we should further explore multilevel treatment options that produce effective, long-lasting results, perhaps requiring a combination of passive (traditional) and active (novel) treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Chronic constipation

Chronic constipation is one of the most common health disorders in all of medicine. Its extent ranges from mild discomfort, which is usually easy to improve, to severe functional limitations that may significantly reduce quality of life and may be refractory to various treatment approaches. Our understanding of the pathomechanism has grown considerably in recent years and has also led to important new therapeutic developments. The resulting treatment options and recommendations are presented in the current update of the S2k constipation guideline in an evidence-based and practical manner. The respective significance of traditional and recent drug developments is classified and categorized in modern "step-up" treatment strategies. In particular, numerous important aspects of everyday practice are addressed, such as questions on long-term treatment and therapeutic options in specific constellations (adequate treatment of constipation in older people, constipation during pregnancy, and drug-induced [especially opioid-induced]constipation).The most important new developments (i.e. new therapeutic approaches, but also re-evaluations of "traditional" laxatives and the importance of careful diagnostics in therapy-refractory patients) are summarized in this article.

A solution for constraining past marine Polar Amplification

Most climate proxies of sea surface temperatures suffer from severe limitations when applied to cold temperatures that characterize Arctic environments. These limitations prevent us from constraining uncertainties for some of the most sensitive climate tipping points that can trigger rapid and dramatic global climate change such as Arctic/Polar Amplification, the disruption of the Atlantic Meridional Overturning Circulation, sea ice loss, and permafrost melting. Here, we present an approach to reconstructing sea surface temperatures globally using paired Mg/Ca - δ18Oc recorded in tests of the polar to subpolar planktonic foraminifera Neogloboquadrina pachyderma. We show that the fidelity of Mg/Ca-based paleoclimate reconstructions is compromised by variations in seawater carbonate chemistry which can be successfully quantified and isolated from paleotemperature reconstructions using a multiproxy approach. By applying the calibration to the last glacial maximum, we show that marine polar amplification has been underestimated by up to 3.0 ± 1.0 °C in model-based estimates.

Prevalence of psychosocial findings and their correlation with TMD symptoms in an adult population sample

Background and aimSome studies suggested an association between Temporomandibular Disorders (TMD) and psychosocial status, but most of them are focused on samples of patients looking for treatment or present limits of sample representativeness. The aim of the present study was to evaluate the psychosocial status in a large sample of adult population, further than to assess its association to TMD symptoms, oral behaviours, and self-reported facial trauma.Resultsthe study sample included 4299 subjects older than 18 years randomly recruited from general population in public spaces during their daily life (1700 Males, 2599 Females mean ± SD age = 40.4 ± 18.1). Psychosocial status and pain-related disability were assessed by means of Patient Health Questionnaire 4 (PHQ-4) and Graded Chronic Pain Scale (GCPS). TMD symptoms were assessed by RDC/TMD and validated screening tools for TMD pain. Oral Behaviours Checklist was used to investigate on oral behaviours. Logistic regression model was used to evaluate the association of the psychosocial status, TMD symptoms, trauma, and oral behaviours. The association was tested using both univariate and multivariate models. The PHQ4 evaluation showed a severe impairment in 4.6% of our sample, moderate in 18.8% and mild in 32.5%. We found a Characteristic Pain Intensity (CPI) level and Interference Score greater that 30 respectively in 36.2% and 22.2% of the study sample. The GCPS status revealed a high disability with severe limitation in 2.5% of the sample, high disability with moderate limitation in 7.0%, low disability high pain intensity in 7.4% and low disability low pain intensity in 37.8%. Anxiety and depression’s levels were significantly associated with gender, TMD pain, coexistence of TMD Pain and sound, and oral behaviours. GCPS status was significantly associated with age, TMD Pain, coexistence of TMD pain and sound, trauma, and oral behaviours.ConclusionsIn the general population, psychosocial impairment is associated to TMD pain, female gender, and report of oral behaviours. Hence, in adults with TMD accompanied by pain, psychosocial status should also be evaluated.

The association between smoking, chronic pain, and prescription opioid use: 2013-2021

It is known that smoking is associated with greater chronic pain. However, little is known about the magnitude of this relationship and its association with prescription opioid use. We examine the association between smoking status and three sets of outcomes: (1) starting and discontinuing opioids, (2) intensity of opioid use, and (3) opioid use and pain outcomes after quitting smoking. We use multinomial logit on adults in the nationally representative 2013–2021 Medical Expenditure Panel Survey linked to the National Health Interview Survey (N = 36,796). Smoking adults made up 16% of the population but used 30% of all opioid prescriptions and 40% of all annual Morphine Milligram Equivalents (MMEs). The 1% of the population that smoked and had severe work limitations due to pain used 20% of all MMEs. Smoking adults were 24% more likely than never-smoking adults to have chronic pain. Among those with pain, smoking adults had 46% higher relative risk of starting opioids compared to never-smoking adults (p < .01), and smoking adults had 6.6 times higher relative risk of continuing opioids the next year compared to never-smoking adults (p < .01). Those smoking and using opioids had 95% higher odds of using a prescribed dosage of 50 MME or more than never-smoking adults. A year after quitting smoking, opioid use declined by 20% and pain declined by 7% compared to those continuing to smoke, with no difference from never-smoking adults after 12 years. Integrating smoking cessation into pain management programs could be highly beneficial to adults with chronic pain. PerspectiveRarely are smoking cessation and pain management programs integrated together. We show that such integration would be highly beneficial by estimating a strong association between smoking cessation and reduced chronic pain, work limitations, and prescription opioid use.

Global Expectations for Bystander Intervention in Domestic Violence: A Scoping Review of Governmental Policies and Community Resources in Eight Countries

Abstract Purpose Over recent years, expectations for bystanders to intervene to interrupt or prevent domestic violence have increased. However, the extent of these expectations and the ways in which bystanders are supported to uphold these expectations remain ambiguous. Drawing on a scoping review methodology, this study aims to map the bystander expectations and advice contained in government policies and community resources across eight countries. Methods We conducted a grey-literature search to identify the three most recent and relevant policy documents from each country, as well as the three most easily-accessible online community resources. We charted key information from each policy and resource, including type of violence and level of prevention; responsibility to intervene and effectiveness of bystander intervention; recognition of danger; and recommended bystander actions. Results The results indicate that the government policies and community resources included in the review held high expectations for bystanders to intervene in domestic violence. However, the information provided on how to safely and effectively intervene was inconsistent in its recognition of the risk posed to bystanders, and often offered contradictory advice. Conclusions An examination of our findings within the context of existing evidence suggests that there are severe limitations to the messages and information presented by the policies and resources. As a matter of urgency, more empirical research is needed to inform the government policies and community resources that encourage bystanders to intervene in domestic violence.

Radiomultiomics: quantitative CT clusters of severe asthma associated with multi-omics.

Lung quantitative computed tomographic (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways. We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort. The same qCT measurements were used to replicate qCT clusters in a subsample of the ATLANTIS asthma cohort (n=97). We performed integrated enrichment analysis using blood, sputum, bronchial biopsies, bronchial brushings and nasal brushings transcriptomics and blood and sputum proteomics to characterize radiomultiomic-associated clusters (RACs). qCT clusters and clinical features in U-BIOPRED were replicated in the matched ATLANTIS cohort. In the U-BIOPRED cohort, RAC1 (n=30) was predominantly female with elevated BMI, mild airflow limitation, normal qCT parameters and upregulation of the complement pathway. RAC2 (n=34) subjects had a lower degree of airflow limitation, airway wall thickness and dilatation, with upregulation of proliferative pathways, including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B (NTRK2/TRKB), and down-regulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signaling and signaling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9. U-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent anovel strategy to identify new molecular pathways in asthma pathobiology.

Predictors of functional status and disability among patients living with chronic kidney diseases at St Paul’s hospital millennium medical college, Ethiopia: findings from a cross-sectional study

BackgroundThe rise in risk factors like obesity, hypertension, and diabetes mellitus has partly led to the increase in the number of patients affected by chronic kidney disease, affecting an estimated 843 million people, which is nearly 10% of the general population worldwide in 2017. Patients with CKD have an increased risk of functional difficulties and disability. This study aimed to assess the level of functional status and disability and its associated factors among patients with chronic kidney attending Saint Paul Hospital, Millennium Medical College, Addis Ababa, Ethiopia.MethodsAn institution-based cross-sectional study was conducted with 302 enrolled study participants through systematic random sampling techniques. Face-to-face interviews and chart reviews were used to collect data using a semi-structured questionnaire adapted from works of literature. The Health Assessment Questionnaire Disability Index (HAQ-DI) was used to assess the functional status and disability of the participants. Data was entered into EPI info version 7 and exported to SPSS version 23 for analysis. Bivariate logistic regression analysis was employed with a p-value less than 0.25. Finally, those variables with a p-value less than 0.05 in multivariate analysis were taken as statistically significant.ResultsA total of 219 (72.5%) CKD patients had moderate to severe functional limitation and disability (HAQ-Di > 0.5-3). Age > 50 years [AOR = 1.65; 95% CI (1.23, 3.15)], being at stage 2 and 3 CKD [AOR = 4.05; 95% CI (1.82, 9.21), being at stage 4 and 5 CKD [AOR = 2.47; 95% CI (1.87, 4.72)], and having MSK manifestations [AOR = 2.97; 95% CI (1.61, 5.55)] were significantly associated with functional status and disability.ConclusionThe findings of this study suggest that CKD-associated functional disabilities are common. The advanced stage of CKD, higher age, and presence of musculoskeletal manifestations appear to be important variables predicting self-reported functional status. Healthcare professionals treating CKD shall be vigilant about the CKD-associated disability, the modifiable predictors, and interventions to limit the CKD-related disability.

Recent Advancements in Prostate Catheters and Stents for Management of Benign Prostatic Hyperplasia.

The prevalence of benign prostatic hyperplasia (BPH) is rising, however, current treatment options present severe complications and limit patient's quality of life. Accordingly, advancements in prostatic catheter and stent designs for use in treating lower urinary tract symptoms (LUTS) in BPH patients have largely expanded in the past five years and we aim to provide an exhaustive summary of recent outcomes. The dual dilation and paxlitaxel eluting Optilume BPH Catheter System enhances promise in catheter-based treatments, providing the longest sustained increase in max urinary flow rate and decrease in post-void residual volume compared to alternative MISTs. Additionally, use of iTiND, along with recent advancements in temporary (EXIME, Prodeon Urocross) and permanent (Zenflow Spring, Butterfly, and ClearRing) stent designs, have demonstrated rapid, lasting, and low-cost LUTS relief with sustained sexual function. Minimally invasive solutions that offer in-office treatment, rapid symptom relief, shorter recovery times, and preservation of sexual function hold great promise in improving outcomes in managing BPH patients with LUTS.

Functioning of post-COVID-19 patients: a cross-sectional study at the outpatient clinic for long-term effects

Background After COVID-19 infection, long-term impacts on functioning may occur. We studied the functioning of patients with post-COVID-19 condition (PCC) and compared them to controls without PCC. Methods This cross-sectional study consisted of 442 patients with PCC referred to rehabilitation at the Helsinki University Hospital (HUS) Outpatient Clinic for the Long-Term Effects of COVID-19, and 198 controls without PCC. Functioning was assessed with a questionnaire including WHODAS 2.0. Patients underwent physical testing including a hand grip strength test (HGST) and a 6-minute walking test (6MWT). Lifestyle was assessed by questionnaire and comorbidities were collected as ICD-10 codes from the HUS Data Lake on the HUS Acamedic platform. Results The WHODAS 2.0 average total score was 34 (SD 18) (moderate functional limitation) for patients with PCC and 6 (SD 8) (normal or mild limitation) for the controls. The disability was higher in all aspects of WHODAS 2.0 in patients with PCC. Bivariate binomial and multivariable regression analyses showed that the presence of comorbidities, anxiety, depression, and smoking predicted a WHODAS 2.0 score of 24 (moderate functional limitation) or above in the PCC group. The average 6MWT distance was 435 m (SD 98 m) in patients with PCC and 627 m (SD 70 m) in controls. HGST measurements showed no significant differences from controls. Conclusions In conclusion, patients with PCC had significantly reduced functioning based on WHODAS 2.0 scores and the 6MWT results. Comorbidities, anxiety, depression, and smoking were associated with moderate or severe limitations in functioning. Findings support that PCC is multifactorial and requires a holistic approach to rehabilitation.

Quantifying the Role of Silicate and Dissolved Nitrogen in Co‐Limiting the Primary and Secondary Productivity of the Bay of Bengal Euphotic Zone

AbstractA single‐column coupled physical and biological model based on the North Pacific Ecosystem Model for Understanding Regional Oceanography (NEMURO) with nitrogen and silicon cycles is adapted for the Bay of Bengal (BoB) environment. The model simulated plankton biomass and nutrients along the track of Bio‐Argos over East and West BoB (from 2016 to 2017) are validated with the observations. The model reasonably simulates the perennial structure of subsurface chlorophyll maximum (SCM). Further, three experiments are carried out to know the limitations in primary and secondary production in terms of nitrogen (NO3 + NH4) and silicate (Si(OH)4) in the open ocean BoB. In a “no‐NO3”experiment, the nitrate limiting term [that is, NO3/(NO3 + KNO3)] is set to zero so that the difference from the control case gives the role of “regenerated production” in the total primary and secondary production. Similarly, a no‐NH4 experiment was conducted to infer the role of “new production.” The new (regenerated) production fuels 85 ± 1% (28 ± 6%) of the living biomass in the East part of open ocean BoB (East BoB). The corresponding values for the west part (West BoB) are 86 ± 1% (42 ± 2%). Among the primary producers, the new (regenerated) production contributed 72 ± 1% (24 ± 6%) in the East BoB and 74 ± 1% (37 ± 2%) in the West BoB. The silicate limits the diatom production by 46% ± 22% (45% ± 27%) of the actual amount of diatom in the East BoB (West BoB) diatom. Surface to 60 m depth, we observed severe nitrate limitation over East BoB and equal limitation of nitrate and silicate over West BoB from June to September; the remaining months suffered from moderate nitrate limitation in both regions. This study shows that nitrate appears to be a limiting nutrient compared to silicate at the surface of both East and West BoB. Since silicicline is deeper than nitracline, silicate is the potential limiting nutrient in BoB from 65 to 105 m depth in all seasons.

Towards a Conversational Ethics of Large Language Models

Abstract Large Language Models are one of the most prominent examples of current uses of AI, and one of the most urgently pursued normative tasks is to make them and their interactive user-interfaces—open-domain chatbots—safe. However, in this paper, we elaborate first on why such a limited view on the permissibility and desirability of their utterances falls conceptually flat, is philosophically insufficient, and leads to severe technological limits. We then propose a positive normative concept, appropriateness, that can provide the required orientation for determining what chatbots may or may not say, and distinguish between technical-discursive, social, and moral appropriateness. Lastly, we explore the requirements for social and conversational contexts to fulfill appropriateness-requirements, and find that positionality is a key element for their position in discourse.

Half the price, twice the gain: How to simultaneously decrease animal numbers and increase precision with good experimental design.

Animal research often involves experiments in which the effect of several factors on a particular outcome is of scientific interest. Many researchers approach such experiments by varying just one factor at a time. As a consequence, they design and analyze the experiments based on a pairwise comparison between two groups. However, this approach uses unreasonably large numbers of animals and leads to severe limitations in terms of the research questions that can be answered. Factorial designs and analyses offer a more efficient way to perform and assess experiments with multiple factors of interest. We will illustrate the basic principles behind these designs, discussing a simple example with only two factors before suggesting how to design and analyze more complex experiments involving larger numbers of factors based on multiway analysis of variance.

Nanostructured NiCo2S4 immobilized on nickel foam as recyclable catalyst for activating peroxymonosulfate toward doxycycline degradation: Performance and mechanism

The existing powder catalysts used in sulfate radical-based advanced oxidation processes (SR-AOPs) commonly suffer from severe limitation due to the difficulty of recycling and inadequate exposure of the active site. In this work, spinel sulfide (NiCo2S4) was uniformly grown on 3D nickel foam (NF) through a one-step hydrothermal route for the activation of peroxymonosulfate (PMS) toward highly efficient degradation of doxycycline (DOX). Due to the synergistic effect of Ni and Co in the NiCo2S4, the NiCo2S4/NF (0.6 g/L) combined with PMS (3.0 mmol L-1) can promote a nearly complete degradation (98.2 %) toward 0.3 mmol/L DOX within 6 min. Density functional theory (DFT) calculations illustrated that the NiCo2S4/NF can adsorb PMS through a unique Ni-S-Co structure and “conducting bridge” mode of NF, accelerating the electron transfer from NiCo2S4/NF to PMS and the subsequent O-O bond cleavage. Especially, the Co/Ni dual-site enhanced the adsorption of PMS and promotes electron transfer to form surface-activated PMS complex (catalyst-PMS*), leading to the generation of surface-bound reactive oxygen species (ROS) on the NiCo2S4 surface. Quenching experiments and ESR tests demonstrated that radicals such as SO4•-, 1O2, •OH and surface-bound ROS play a vital role in DOX degradation. Moreover, the potential mechanism and pathway of DOX degradation are reasonably deduced by investigating and analyzing the intermediates with liquid chromatography-mass spectromsetry (LC-MS). Consequently, this study provides a deep insight on the systhsis of spinel sulfide and its intrinsic mechanism of PMS activation toward organic contaminant degradation.

Use of NIR in COVID-19 Screening: Proof of Principles for Future Application.

The COVID-19 pandemic that affected the world between 2019 and 2022 showed the need for new tools to be tested and developed to be applied in global emergencies. Although standard diagnostic tools exist, such as the reverse-transcription polymerase chain reaction (RT-PCR), these tools have shown severe limitations when mass application is required. Consequently, a pressing need remains to develop a rapid and efficient screening test to deliver reliable results. In this context, near-infrared spectroscopy (NIRS) is a fast and noninvasive vibrational technique capable of identifying the chemical composition of biofluids. This study aimed to develop a rapid NIRS testing methodology to identify individuals with COVID-19 through the spectral analysis of swabs collected from the oral cavity. Swab samples from 67 hospitalized individuals were analyzed using NIR equipment. The spectra were preprocessed, outliers were removed, and classification models were constructed using partial least-squares for discriminant analysis (PLS-DA). Two models were developed: one with all the original variables and another with a limited number of variables selected using ordered predictors selection (OPS-DA). The OPS-DA model effectively reduced the number of redundant variables, thereby improving the diagnostic metrics. The model achieved a sensitivity of 92%, a specificity of 100%, an accuracy of 95%, and an AUROC of 94% for positive samples. These preliminary results suggest that NIRS could be a potential tool for future clinical application. A fast methodology for COVID-19 detection would facilitate medical diagnoses and laboratory routines, helping to ensure appropriate treatment.