Significant Inter-individual Variation Research Articles

Predicting Postprandial Glycemic Responses With Limited Data in Type 1 and Type 2 Diabetes.

A core challenge in managing diabetes is predicting glycemic responses to meals. Prior work identified significant interindividual variation in responses and developed personalized forecasts. However, intraindividual variation is still not well understood, and the most accurate approaches require invasive microbiome data. We aimed to investigate (1) whether postprandial glycemic responses (PPGRs) can be predicted with limited data and (2) sources of intraindividual variation. We used data collected from 397 people with Type 1 Diabetes (T1DEXI) and 100 people with Type 2 Diabetes (ShanghaiT2DM) who wore continuous glucose monitors (CGMs) and logged meals. Using dietary, demographic, and temporal features, we predicted 2 hours PPGR, and peak 2 hours postprandial glucose rise (Glumax). We evaluated the contribution of food features (eg, macronutrients, food category) and use of personal training data and investigated intraindividual variability in responses. We achieved comparable accuracy to prior work for PPGR (T1DEXI R = 0.61, ShanghaiT2DM R = 0.72) and Glumax (T1DEXI R = 0.64, ShanghaiT2DM R = 0.73), without using invasive data like microbiome. Including food category features led to higher accuracy than macronutrients alone. Analysis of glycemic responses to duplicate meals identified time of day (PPGR: T1DEXI P < .05 for lunch, ShanghaiT2DM P < .001 for lunch and dinner) and menstrual cycle (Glumax: P < .05 for perimenstrual) as sources of variability. We demonstrate that in individuals with T1D and T2D, glycemic responses to meals can be predicted without personalized training data or invasive physiological data.

Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis-With Special Reference to Delayed Hypersensitivity Reactions.

Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR. Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented. A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients. This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR.

Anti-mullerian hormone (AMH) in pregnant buffaloes: maternal and fetal plasma concentrations and immunolocalization in the fetal gonads.

Anti-Müllerian Hormone (AMH), a member of the TGF-β superfamily, plays a critical role in mammalian fertility. This study aimed to investigate AMH concentrations in pregnant buffalo cows and their fetuses, and to characterize the cellular distribution and immunolocalization of AMH within fetal gonads. Gonads were collected from 12 male and 14 female buffalo fetuses, fixed in 10% buffered formalin, and processed for routine histological analysis and immunohistochemical localization of AMH. Blood samples were collected from 26 pregnant buffalo cows and their corresponding fetuses into EDTA-coated tubes. AMH levels in both maternal and fetal blood were quantified using a commercially available bovine AMH ELISA kit. Significant (p < 0.05) inter-individual variations in maternal and fetal AMH concentrations were observed. In males, fetal AMH concentrations increased significantly with gestational age, with levels substantially higher compared to females at all gestational ages (52-1222 times higher). Immunohistochemistry revealed intense AMH immunoreactivity in the cytoplasm of pre-Sertoli cells in male fetuses. In females, no significant correlation was found between fetal AMH concentrations and follicular populations, although intense AMH immunostaining was observed in the cytoplasm of oocytes within primordial follicles. These findings suggest that fetal AMH concentrations in buffaloes are influenced by gestational age and sex, and that fetal AMH likely does not readily cross the placental barrier. Further investigations are warranted to elucidate the intricate role of AMH in gonadal development and function in buffaloes.

Microneedle-Based Electrochemical Array Patch for Ultra-Antifouling and Ultra-Anti-Interference Monitoring of Subcutaneous Oxygen.

Oxygen saturation is a crucial indicator in the management of various diseases and in preoperative diagnosis, and the detection of oxygen content is valuable in guiding clinical treatment. However, as the classical and dominant oxygen detection strategies, current photoelectric oximeters and electrochemical-based blood gas analyzers often suffer from significant interindividual variation and poor compliance, respectively. In recent years, wearable microneedles (MNs) for analyzing biomarkers in interstitial fluid (ISF) have received great attention and recognition mainly for the reason that the content of the substances distributed in ISF has a better correlation with that in blood circulation compared with other body fluids such as sweat and saliva. Herein, an MN-based electrochemical array system was developed for continuous subcutaneous oxygen sensing, in which gold-modified commercial acupuncture MNs were used as the sensing units, and a tailored mini-workstation, a nonwoven fabric, and a water and air isolation membrane were integrated to fabricate a wearable array patch. Notably, a multifunctional swelling resin with good biocompatibility was adopted to decorate the MN surface as a protective layer and as an electrolyte gel. The swelling resin featured the ability to reduce epidermis secretions during the sensor array penetrating the skin and to decrease the interference of other biomolecules in ISF for oxygen assay during measurement. This proposed array patch can perform the subcutaneous oxygen analysis in the physiological range of 6-150 mmHg with high sensitivity (0.3817 μA/mmHg) and low theoretical limit of detection (5.06 mmHg). It also showed decent stability and selectivity in the presence of several kinds of exogenous and endogenous substances. Finally, the patch accomplished continual monitoring of the subcutaneous oxygen content during long-term physical exercise, showing great potential in providing warning about the hypoxia status of the human body. It could be foreseen that this high-performance patch will play an active role in respiratory disease evaluation, surgical monitoring, and public health care.

Motor styles in action: Developing a computational framework for operationalization of motor distances

Aside from some common movement regularities, significant inter-individual and inter-trial variation within the same individual exists in motor system output. However, there is still a lack of a robust and widely adopted solution for quantifying the degree of similarity between movements. We therefore developed an innovative approach based on the Procrustes transformation to compute 'motor distance' between pairs of kinematic data. As a proof of concept, we tested this on a dataset of reach-to-grasp movements performed by 16 participants while acting with the same confederate. Using the information of wrist velocity, acceleration, and jerk, the proposed technique was able to correctly estimate smaller distances between movements performed by the confederate compared with those of participants. Moreover, the reconstructed pattern of inter-subject distances was consistent when computed either on precision grip prehension or whole hand prehension, suggesting its suitability for the investigation of 'motor styles'. The definition of a solid approach to 'motor distance' computation, therefore, opens the way to new research lines in the field of movement kinematics.

Generative modeling of the Circle of Willis using 3D-StyleGAN

Generative modeling of the Circle of Willis using 3D-StyleGAN

Self-distillation with beta label smoothing-based cross-subject transfer learning for P300 classification

Self-distillation with beta label smoothing-based cross-subject transfer learning for P300 classification

RNA sequencing analysis reveals distinct gene expression patterns in infrapatellar fat pads of patients with end-stage osteoarthritis or rheumatoid arthritis

RNA sequencing analysis reveals distinct gene expression patterns in infrapatellar fat pads of patients with end-stage osteoarthritis or rheumatoid arthritis

Personalized blood pressure estimation using multiview fusion information of wearable physiological signals and transfer learning

Personalized blood pressure estimation using multiview fusion information of wearable physiological signals and transfer learning

Modulation of gut microbiome in response to the combination of Escherichia coli Nissle 1917 and sugars: a pilot study using host-free system reflecting impact on interpersonal microbiome.

The differential effects of probiotic, prebiotic, and synbiotic formulations on human health are dictated by the inter-individual gut microbial profile. The effects of probiotics such as Escherichia coli Nissle 1917 (ECN) on gut microbiota may vary according to the microbiome profiles of individuals and may be influenced by the presence of certain carbohydrates, which can impact microbial community structure and treatment results. Processed fecal samples from donors having contrasting lifestyles, dietary patterns, and disease histories were mixed with 5 × 106 CFU/mL ECN with or without 1% (w/v) sugars (glucose, galactose, or rice starch) in a host-free system. Post-incubation, 16 s rRNA sequencing was performed. Microbial diversity and taxonomic abundance were computed in relation to the probiotic, prebiotic, and synbiotic treatment effects and interpersonal microbiome variance. Baseline gut microbial profiles showed significant inter-individual variations. ECN treatment alone had a limited impact on the inter-personal gut microbial diversity and abundance. Prebiotics caused a substantial enrichment in Actinobacteria, but there were differences in the responses at the order and genus levels, with enrichment shown in Bifidobacterium, Collinsella, and Megasphaera. Subject B exhibited enrichment in Proteobacteria and Cyanobacteria, but subject A showed more diversified taxonomic alterations as a consequence of the synbiotic treatments. Despite negligible difference in the α-diversity, probiotic, prebiotic, and synbiotic treatments independently resulted in distinct segregation in microbial communities at the β-diversity level. The core microbiota was altered only under prebiotic and synbiotic treatment. Significant correlations primarily for minor phyla were identified under prebiotic and synbiotic treatment. The interindividual microbiome composition strongly influences the effectiveness of personalized diet and treatment plans. The responsiveness to dietary strategies varies according to individual microbiome profiles influenced by health, diet, and lifestyle. Therefore, tailored approaches that consider individual microbiome compositions are crucial for maximizing gut health and treatment results.

5065 Cyproterone Acetate Versus Spironolactone In Transgender Women Commencing Estradiol: A Randomized Controlled Trial

Abstract Disclosure: L.M. Angus: Advisory Board Member; Self; Kirin Brewery. Speaker; Self; Kirin Brewery. S. Leemaqz: None. A. Kasielska-Trojan: None. M. Mikołajczyk: None. J. Doery: None. J.D. Zajac: None. A.S. Cheung: None. Background: Transgender women commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol to assist with feminization. However, the optimal anti-androgen is unclear. We aimed to assess the effect of these anti-androgens on breast development and hypothesized that cyproterone acetate would result in greater breast development than spironolactone due to greater androgen receptor antagonism and suppression of serum total testosterone. Design: Double-blind, randomised controlled trial Methods: Transgender women newly commencing estradiol were randomized to spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months. The primary outcome was measurement of breast development via breast chest distance with secondary outcomes of estimated breast volume using the BreastIdea Volume Estimator application and serum total testosterone using LCMS. Results: Fifty-five participants were included in per protocol analysis (cyproterone acetate group n=28, spironolactone group n=27). Baseline age, body mass index, breast indices, serum estradiol and serum total testosterone were comparable. At six months, the mean (standard deviation) breast chest distance was 9.2cm (3.0) in the cyproterone group versus 8.3cm (2.7) in the spironolactone group (p=0.27). The mean (SD) estimated breast volume was 190.25 mL (158.60) in the cyproterone acetate group and 157.84mL (112.03) in the spironolactone group (p=0.39) with significant inter-individual variation (range 20.27 - 787.77 mL). The mean (SD) serum total testosterone was 1.48 nmol/L (3.45) in the cyproterone acetate group and 4.29 nmol/L (5.44) in the spironolactone group (p=0.04). Serum estradiol levels were comparable. Use of cyproterone acetate was associated with mild hyperprolactinaemia and spironolactone with an increase in serum urea and creatinine. Conclusions: Choice of anti-androgen should be individualised based on clinician and patient preference, with consideration of associated side effects. Further research is needed to optimise breast development in transgender women. Presentation: 6/3/2024

Frequency of pharmacogenomic variants affecting safety and efficacy of immunomodulators and biologics in a South Asian population from Sri Lanka

BackgroundImmunomodulators are important for management of autoimmune diseases and hematological malignancies. Significant inter-individual variation in drug response/reactions exists due to genetic polymorphisms. We describe frequency of identified genetic polymorphisms among Sri Lankans.MethodsSri Lankan data were obtained from an anonymized database of 670 participants. Data on variants and global distribution of Minor Allele frequency (MAF) of other populations (South Asian, Ashkenazi-Jewish, East-Asian, European-Finnish, European-non-Finnish, Latino-American, African/African-American) were obtained from pharmGKB online database.ResultsSLC19A1 (rs1051266) variant had a MAF (95% CI) of 63.3% (60.7–65.9). Other common variants included FCGR3A (rs396991), MTHFR (rs1801133), ITPA (rs1127354), CYP2C9*3 (rs1057910) and NUD15*3 (rs116855232), with MAFs of 35.3% (32.7–37.9), 12.2% (10.4–13.9), 10.9% (9.2–12.6), 9.8% (8.2–11.4), 8.3% (6.8–9.8) respectively. Less commonly present variants included CYP2C9*2 (rs1799853) (2.5%[1.7–3.4]), TPMT*3C (rs1142345) (1.9%[1.1–2.6]), TPMT*3B (rs1800460) (0.2%[0–0.5]), CYP3A5*6 (rs10264272) (0.2%[0–0.4]) and CYP3A4*18 (rs28371759) (0.1%[0–0.2]). The SLC19A1 (rs1051266), NUD15*3 (rs116855232), CYP2C9*3 (rs1057910), FCGR3A (rs396991), and ITPA (rs1127354) showed significantly higher frequencies in Sri Lankans compared to many other populations, exceptions include FCGR3A in Ashkenazi-Jewish and ITPA in East-Asians. Conversely, MTHFR (rs1801133), TPMT*3B (rs1800460), and CYP2C9*2 (rs1799853) were significantly less prevalent among Sri Lankans than in many other populations. Sri Lankans exhibited lower prevalence of TPMT*3C (rs1142345) compared to European-non-Finnish, Latino-Americans, and African/African-Americans; CYP3A4*18 (rs28371759) compared to East-Asians; and CYP3A5*6 (rs10264272) compared to African/African-Americans and Latino-Americans.ConclusionSri Lankans exhibit higher frequencies in variants reducing methotrexate efficacy (SLC19A1), increasing azathioprine myelotoxicity (NUDT15), and lower frequencies in variants linked to increased azathioprine toxicity (TPMT*3B, TPMT*3C), reduced tacrolimus efficacy (CYP3A4*18), and methotrexate toxicity risk (MTHFR). Beneficial variants enhancing rituximab efficacy (FCGR3A) are more prevalent, while those reducing tacrolimus dosage (CYP3A5*6) are less common. This highlights need for targeted medication strategies to improve treatment outcomes.

Comparison between a Flash Glucose Monitoring System and a Portable Blood Glucose Meter for Monitoring of Cats with Diabetic Ketosis or Ketoacidosis.

Cats with diabetic ketosis or ketoacidosis DK(A) require intensive glucose monitoring. The aim of this study was to assess the agreement between a portable blood glucose meter (PBGM) and a flash glucose monitoring system (FGMS; FreeStyle Libre 2.0 Abbott®) measuring interstitial glucose in cats with DK(A). Ten client-owned cats with naturally occurring DK(A) were prospectively enrolled. Glucose concentrations were assessed with both methods every 1-3 h until resolution of DK(A), and every 4-8 h thereafter. While the median FGMS measured glucose concentration (14.3 mmol/L) was significantly lower than the median PBGM measured glucose concentration (19 mmol/L) (p < 0.001), the overall correlation between the FGMS and PBGM was high (r = 0.88; p < 0.001). In the Parkes error grid analysis, 98.3% of measurements fell in zones A and B. Bland-Altman plot analysis demonstrated that in the low glycaemic range (BG < 5.5 mmol/L), 50% of FGMS measurements deviated more than ±0.83 mmol/L, and in the high glycaemic range (BG > 5.5 mmol/L), 81% of results deviated >15% from the PBGM measurements. There was significant inter-individual variation in the difference between glucose concentrations measured by the FGMS and PBGM (p < 0.001). In spite of being more easily tolerated and easier to use, currently this method cannot be recommended for routine monitoring of cats with DK(A).

The natural menstrual cycle revisited – can natural cycle be trusted

BackgroundThe serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the best endocrine profile and whether mid-luteal serum P4 levels are always sufficient to support implantation and early pregnancy. The question has become more relevant in relation to fertility treatment, as more frozen embryo transfer cycles are performed in the natural cycle. Moreover, can serum hormone levels and covariates measured during the follicular phase (FP), such as Follicle Stimulation Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Anti-Mullerian Hormone (AMH) and Antral Follicle Count (AFC), be used to predict P4 levels during the luteal phase (LP)?ResultsThis observational prospective cohort study analysed 26 healthy women with a cycle length between 21–35 days and a body mass index (BMI) < 30 kg/m2. Blood sampling started on the fifth day of the menstrual cycle and continued every fifth day until the next cycle. The procedure was repeated for a total of three cycles. The study found that only ten women had a P4 level greater than 30 nmol/L on cycle day 20 or 25 in all three cycles. In total, only 45 cycles out of 77 cycles had serum P4 levels ≥ 30 nmol/L.The E2 level ≥ 345 pmol/L on cycle day 10 proved to be predictive of a P4 level of ≥ 30 nmol/L on either day 20 or day 25 with a sensitivity of 57% and a specificity of 89%. No other covariates, including the FSH level cycle day 5, LH levels during the follicular phase, age, weight, AFC and AMH cycle day 5 correlated with LP P4 levels.ConclusionsA significant correlation between FP E2 levels cycle day 5 (> 131pmol/L) and cycle day 10 (> 345pmol/L) and a LP P4 level ≥ 30 nmol/l was found; thus, the FP E2 level is a predictor of corpus luteum competence. Our findings highlight the existence of suboptimal P4 levels during the LP and a significant inter-individual and intra-cycle variation in P4 levels during the LP in regular menstruating women.

Gut microbial factors predict disease severity in a mouse model of multiple sclerosis

Gut bacteria are linked to neurodegenerative diseases but the risk factors beyond microbiota composition are limited. Here we used a pre-clinical model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), to identify microbial risk factors. Mice with different genotypes and complex microbiotas or six combinations of a synthetic human microbiota were analysed, resulting in varying probabilities of severe neuroinflammation. However, the presence or relative abundances of suspected microbial risk factors failed to predict disease severity. Akkermansia muciniphila, often associated with MS, exhibited variable associations with EAE severity depending on the background microbiota. Significant inter-individual disease course variations were observed among mice harbouring the same microbiota. Evaluation of microbial functional characteristics and host immune responses demonstrated that the immunoglobulin A coating index of certain bacteria before disease onset is a robust individualized predictor of disease development. Our study highlights the need to consider microbial community networks and host-specific bidirectional interactions when aiming to predict severity of neuroinflammation.

Vascularity evaluation of the equine tarsocrural and proximal intertarsal joint septum, and comparative analysis of two arthroscopic transection techniques.

To evaluate vascularity of the synovial membrane covered septum (SMS) separating the tarsocrural (TC) and proximal intertarsal (PIT) joints (Part 1) and compare two methods of transection, electrosurgical or Ferris Smith rongeur (FS rongeur) (Part 2). Experimental study. Part 1, 10 SMS (n = 5 horses). Part 2, six horses (n = 12 tarsi). In part 1, SMS harvested postmortem were each divided into eight regions of interest (ROIs), processed for histology, and immunostained with anti-α-actin antibody for blood vessel identification. Vascular density was calculated for each ROI. Data was compared within and between horses. In part 2, six horses underwent TC arthroscopy. Each limb was randomly assigned to undergo either electrosurgical or FS rongeur SMS transection. SMS transection and total operative time were recorded. Intraoperative hemorrhage was scored. Data was compared between both techniques. Significant interindividual variations in SMS vascular density were detected (p = .02), but there were no differences among ROIs. No differences in the transection time were detected between electrosurgery (4.83 ± 0.54 min) and FS rongeur (4.33 ± 0.67 min). No differences were found in intraoperative hemorrhage scores between techniques. Vascularity within the SMS varies among horses but not within its regions. Electrosurgical or FS rongeur transection of the medial SMS during tarsocrural arthroscopy is a rapid technique and improves surgical access to the dorsal compartment of the PIT.

The role of caffeine in headache disorders.

Caffeine is known to have both beneficial and adverse effects in individuals with headache disorders. This review describes recent findings regarding caffeine that are relevant to headache disorders and puts these findings into the context of clinical management. Preclinical studies show that caffeine has complex effects on sleep, brain blood flow, and intracranial pressure that may depend on the timing of caffeine intake relative to the sleep-wake cycle. Caffeine metabolism may have significant inter-individual variation that influences its therapeutic and/or adverse effects. Caffeine has acute therapeutic benefit for some primary headache disorders. For migraine, this benefit is predominantly in milder headache without cutaneous allodynia. High levels of caffeine intake may contribute to progression of headache disorders. Caffeine-containing combination analgesics commonly cause medication overuse headache. Abrupt reduction in caffeine consumption is a trigger for migraine that may be important in situations including the hospital setting, religious and cultural fasting, and pregnancy. There is not sufficient evidence to support universal guidelines for the use of dietary and medicinal caffeine in headache disorders. A sensible approach based upon available evidence is to limit dietary caffeine intake to moderate amounts with consistent timing before noon, and to use caffeine-containing combination analgesics infrequently for milder headache.

Variations of the popliteal artery in human fetuses: preliminary study

IntroductionThis paper provides an in-depth analysis of the anatomical and morphometrical attributes of the popliteal artery (PA) in human fetuses. Additionally, it showcases significant interindividual variation in branching patterns, which are of great clinical importance in the context of vascular surgery and interventional radiology.AimThe purpose of this research was to systematically examine and categorize the anatomical and morphometrical diversities observed in the PA among a 166 sample of human fetuses at various gestational stages, spanning from 16 to 30 weeks of pregnancy.Material and methodsThe latex was injected into the 166 PA within the fetal specimens to visually analyze their anatomical features, and high-resolution digital images were captured at 24-bit color depth for detailed analysis.Results and DiscussionThe PAs were systematically classified into three distinct categories, further subcategorized into specific types. The classification system employed was based on the framework established initially by Lippert and Pabst, with modifications by Kim. The results of the analysis revealed the following distribution: Category I – it was mainly detected in the majority of specimens, comprising 144 cases (86.7%) of the sample population, and represented the most common anatomical configuration; Category II – it was found in 19 specimens (11.4%) of the total sample population (this category represented a less common anatomical variation within the PA); Category III – the rarest anatomical configuration observed in only 3 specimens (1.8%) from the sample population.ConclusionsThe frequent occurrence of short tibiofibular trunks in PA may be due to incidental lesions or postnatal developmental changes, highlighting the need for further research.

Fatigue risk assessment of a Helicopter Emergency Medical Service crew working a 24/7 shift pattern: results of a prospective service evaluation

BackgroundThe work of Helicopter Emergency Medical Services (HEMS) teams crosses the boundaries of several high-risk occupations including medicine, aviation, and transport. Working conditions can be challenging and operational demands requires a 24-h rota, resulting in disruption of the normal circadian rhythm. HEMS crews are therefore prone to both mental and physical fatigue. As fatigue in medical providers is linked to poor cognitive performance, degradation of psychomotor skills and error, this study aimed to explore the existence of predictable patterns of crew-fatigue in a HEMS service.MethodsHEMS medical crew members working a 3-on 3-off forward rotating rota with a 5-week shift cycle were asked to do psychomotor vigilance tests (PVT) as an objective measure of fatigue. PVT testing was undertaken at the start, mid- and at the end of every shift during a full 5-week shift cycle. In addition, they were asked to score subjective tiredness with the Samn-Perelli Fatigue Scale (SPFS), and to keep a Transport Fatigue Assessment shift log, wherein they noted shift characteristics potentially related to fatigue. Primary outcome of interest was defined as the change in PVT and SPFS scores over time.ResultsMean baseline resting PVT in milliseconds at the start of the study period was 427 [390–464]. There was an overall trend towards higher PVT-scores with shift progression mean [95% CI] PVT at the start of shifts 447 [433–460]; halfway through the shift 452 [440–463]; end of the shift 459 [444–475], p = 0.10), whereas SPFS scores remained constant. Within a 5 week forward-rotating cycle, an overall trend towards a gradual increase in both average PVT (from 436 [238–454] to 460 [371–527, p = 0.68] ms;) and SPFS (from 2.9 [2.6–3.2] to 3.6 [3.1–4.0], p = 0.38) was observed, although significant interindividual variation was present. Reported SPFS scores ≥ 4 (moderate fatigue) were mainly related to workload (number of jobs) and transport mode (car-based shifts).ConclusionAn overall trend towards a decline in psychomotor vigilance and an increase in self-reported tiredness was found for HEMS crew over a 5-week shift cycle. Using a bespoke predictive fatigue tool on a day-to-day basis could increase fatigue awareness and provide a framework to which relevant mitigating options can be applied.

Human–machine cooperation meta-model for clinical diagnosis by adaptation to human expert’s diagnostic characteristics

Artificial intelligence (AI) using deep learning approaches the capabilities of human experts in medical image diagnosis. However, due to liability issues in medical decisions, AI is often relegated to an assistant role. Based on this responsibility constraint, the effective use of AI to assist human intelligence in real-world clinics remains a challenge. Given the significant inter-individual variations in clinical decisions among physicians based on their expertise, AI needs to adapt to individual experts, complementing weaknesses and enhancing strengths. For this adaptation, AI should not only acquire domain knowledge but also understand the specific human experts it assists. This study introduces a meta-model for human–machine cooperation that first evaluates each expert’s class-specific diagnostic tendencies using conditional probability, based on which the meta-model adjusts the AI’s predictions. This meta-model was applied to ear disease diagnosis using otoendoscopy, highlighting improved performance when incorporating individual diagnostic characteristics, even with limited evaluation data. The highest accuracy was achieved by combining each expert’s conditional probabilities with machine classification probability, using optimal weights specific to each individual’s overall classification accuracy. This tailored model aims to mitigate potential misjudgments due to psychological effects caused by machine suggestions and to capitalize on the unique expertise of individual clinicians.