Adsorption within continuous renal replacement therapy (CRRT) circuits may reduce exposure to echinocandins. Because micafungin is highly protein bound, the behavior of its unbound fraction during CRRT remains difficult to characterize. We assessed unbound micafungin disappearance from a central compartment and late release/desorption in a protein-free in vitro CRRT model. Micafungin stability was assessed in a 5-L bag of Hemosol™ B0 over 8 h. In the NeckEpur model, a 5-L protein-free central compartment was circulated at 200 mL/min for 6 h through either a polyacrylonitrile hemofilter (ST™150; post-dilution continuous veno-venous hemofiltration [CVVH], 2.5 L/h) or a polysulfone hemofilter (AV™1000). For AV™1000, one run used CVVH (2.5 L/h) and one used continuous veno-venous hemodiafiltration (CVVHDF; dialysis 1.5 L/h plus filtration 1.0 L/h). Initial micafungin concentrations in the central compartment were 2.18 mg/L or approximately 6.8 mg/L. Concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a lower limit of quantification (LLOQ) of 0.1 mg/L. Apparent central-compartment clearance (Cl_CC), sieving coefficient (Sc), and extraction coefficient (EC) were used to describe disappearance from the circuit, filtration, and late release. Sensitivity analyses replaced values < LLOQ by LLOQ/2 or LLOQ/√2. Segmental sampling and within-filter mass balance were used descriptively to localize loss within the extracorporeal system. Micafungin was stable in Hemosol™ B0 over 8 h (- 5.2 ± 0.5%). With ST™150 at 2.18 mg/L, C_CC reached the LLOQ by 200 min and was below the LLOQ thereafter; apparent Cl_CC was approximately 6 L/h, effluent concentrations were not measurable, and limited late release was estimated over 120-200 min. With ST™150 at approximately 6.8 mg/L, elimination from the central compartment was 92 ± 4% at 6 h (apparent Cl_CC 4.9 ± 0.2 L/h), with within-filter contributions from measurable effluent removal (54 ± 6%) and non-effluent loss (46 ± 6%); small late release was compatible with negative EC values during 180-360 min. For AV™1000, two exploratory runs-one CVVH and one CVVHDF-showed rapid disappearance from the central compartment, with C_CC below the LLOQ by 120 min, no measurable effluent concentrations, and no negative EC values. Sensitivity analyses for values < LLOQ changed the numerical Cl_CC estimates but not the overall pattern. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution. In this exploratory protein-free in vitro model, unbound micafungin rapidly disappeared from the CRRT circuit with both tested filter systems. ST™150 showed measurable effluent removal at higher concentrations and limited late release, whereas both exploratory AV™1000 runs showed rapid disappearance without detectable late release. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution. These findings characterize unbound micafungin-circuit interactions under the tested conditions; their clinical translation will depend on in vivo protein binding and rebinding kinetics. Micafungin is an antifungal drug frequently used in critically ill patients, including patients who require continuous renal replacement therapy (CRRT). During CRRT, drug may be removed into the effluent or lost by adsorption within the circuit. Because micafungin is highly protein bound, we specifically studied the unbound fraction, since only this free fraction is pharmacologically active and able to interact directly with the extracorporeal circuit. The experiments used a protein-free in vitro CRRT model with two filter systems: the ST™150 polyacrylonitrile-derived filter during continuous veno-venous hemofiltration (CVVH), and the AV™1000 filter in two exploratory runs, one during CVVH and one during continuous veno-venous hemodiafiltration (CVVHDF). Unbound micafungin disappeared rapidly from the extracorporeal circuit with both filter systems. With ST™150 at higher concentration, within-filter disappearance included both measurable effluent removal and non-effluent loss, and limited late release was compatible with desorption. In the two exploratory AV™1000 runs, the same overall pattern was observed: rapid disappearance from the central compartment, no measurable effluent concentrations, and no detectable late release. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution. Because this was a protein-free model, the study provides mechanistic information about free micafungin–circuit interactions rather than direct bedside dosing recommendations. Translation to in vivo exposure will depend on protein binding and rebinding kinetics.
Current guidelines recommend surveillance or diagnostic lobectomy for indeterminate thyroid nodules. Although radiofrequency ablation (RFA) has emerged as a potential alternative, its role remains controversial. Functional imaging modalities, including 99mTc-methoxyisobutylisonitrile scintigraphy and ¹⁸F-fluorodeoxyglucose positron emission tomography, have been used to support risk stratification. This study evaluated the mid-term outcomes of RFA and their predictors in a functionally screened cohort of patients with indeterminate thyroid nodules. This retrospective cohort study included 109 patients with Bethesda category III or IV thyroid nodules who underwent RFA after functional imaging-based evaluation between January 2018 and November 2024. The primary outcome was local treatment failure (LTF), defined as the first occurrence of nodule regrowth, an increase in vital volume, or repeated indeterminate cytology. The secondary outcome was complete disappearance of the nodule. Supplementary outcomes included the volume reduction rate, symptom and cosmetic scores, and biochemical markers. During a median follow-up of 2.2 years (range, 0.7-6.8 years), LTF occurred in 15 of 109 patients (13.8%), whereas complete disappearance was observed in 9 (8.3%) patients. The 3-year LTF-free probability and cumulative incidence of complete disappearance were 85.4% and 6.5%, respectively. Significant reductions were observed in the nodule volume, symptom scores, cosmetic scores, and free T4 and thyroglobulin levels. A greater initial maximum nodule diameter was independently associated with a higher likelihood of LTF (hazard ratio [HR] per 1-cm increase, 2.35; 95% confidence interval [CI], 1.23-4.48; P = 0.010) and a lower likelihood of complete disappearance (HR, 0.16; 95% CI, 0.04-0.60; P = 0.006). At 3 years, 93% of the tumors with an initial diameter <3.0 cm remained free of LTF, whereas no tumors >2.1 cm achieved complete disappearance. In this functionally screened cohort of patients with indeterminate thyroid nodules, RFA demonstrated acceptable outcomes with volume reduction and symptom relief, particularly in patients with nodules <3 cm.
In dairy production, Hermetia illucens oil (HIO) could represent a more sustainable energy source than oil palm products, but no in vivo information is available on the effects of this strategy on ruminal biohydrogenation and microbial-derived lipids [odd- and branched-chain fatty acids (FA) and dimethyl acetals (DMA)]. To address this knowledge gap, two balanced groups of 13 Valdostana Red Pied cows were fed a 70:30 forage-to-concentrate ratio diet, differing only for its supplemental lipid source: fractionated palm oil (FPO) or HIO (3.4% of concentrate dry matter). At the beginning and after 50 days of treatments, ruminal fluid was collected for a detailed characterization of lipids. Ruminal fluid of HIO cows showed a 25% decrease in total FA content relative to FPO, which might be explained by extensive ruminal disappearance of 12:0 (the main FA in HIO). Dietary HIO slightly reduced biohydrogenation completeness (-1.6%; P = 0.014) without favoring alterations that lead to the trans-10 pathway (e.g., without increasing trans-10 18:1/trans-11 18:1 ratio; P = 0.719). Just a few changes in ruminal FA composition appear to be explained by differences in FA intake (e.g., in 12:0 and 16:0; P < 0.001), whereas most variations would probably derive from an indirect effect of HIO promoting minor pathways of biohydrogenation and alternative metabolic processes, as supported by increases (P < 0.05) in the proportion of oxo-18:0 isomers and most BH intermediates with at least one double bond in Δ12 to Δ16 positions, compared with FPO. Changes in odd- and branched-chain FA and in DMA support that HIO affects ruminal FA profile through potential variations in ruminal microbial composition. The relative proportion of individual DMA was also modified, whereas total DMA content was not affected (P = 0.146). Overall, the minor effects of HIO on biohydrogenation, compared with FPO, supports the use of this alternative lipid source in dairy cow feeding. The oil extracted from black soldier fly (Hermetia illucens) larvae has recently emerged as a sustainable and innovative feed ingredient. Conventional fats are often included in the diets of dairy cows, but some of them are associated with negative environmental impact, such as those derived from oil palm cultivation. The aim of this study was to characterize the effects of replacing palm oil by black soldier fly oil on the lipid metabolism in the rumen of cows, which is a key aspect determining the digestion and subsequent utilization of lipids for milk fat production. Surprisingly, we observed a decrease in total fat content in the ruminal fluid of cows fed the black soldier fly oil, which was associated with an extensive disappearance of lauric acid (the most abundant fatty acid in the insect oil). The study of lipids that represent biomarkers of ruminal microbiota suggest possible changes in this microbial community, which may derive, at least in part, from the antimicrobial effect of lauric acid. Overall, our results suggest that H. illucens oil can be used in dairy cow diets without detrimental effects on ruminal lipid metabolism, as we observed only minimal changes in metabolic pathways compared to the use of palm oil, thus supporting its potential use as a sustainable feed ingredient.
Sex differences in chronic kidney disease (CKD) are recognised, but how they change across the menopausal transition-and how this affects therapeutic opportunities in primary care-remains unclear. We performed a cross-sectional analysis of 9 526 adults from the ONDAAS primary care study with same-day serum creatinine and urine albumin-to-creatinine ratio (ACR). eGFR was estimated with CKD-EPI 2021 and CKD classified by Kidney Disease: Improving Global Outcomes 2024 eGFR (G) and albuminuria (A) categories. Using age 50 years as a proxy for menopause, we fitted age-stratified logistic regression models for CKD G3-G5 (eGFR <60 mL/min/1.73 m²) and for A2-A3 albuminuria, and applied KDIGO 2024 criteria to estimate eligibility for renoprotective and cardioprotective therapies. Women were 56.5% and had higher mean eGFR (84.6 vs 81.1 mL/min/1.73 m²) and lower median ACR (7.0 vs 8.3 mg/g) than men. <50 years, CKD G3 was rare in women (G3a 0.2%, G3b 0.0%); female sex reduced odds of CKD G3-G5 (aOR 0.18, 95% CI 0.05-0.69), while A2-A3 albuminuria strongly predicted CKD (aOR 33.39, 95% CI 10.41-107.13). ≥50 years, sex differences in CKD disappeared (aOR 1.01, 95% CI 0.87-1.16) and age dominated (aOR 1.13/year, 95% CI 1.12-1.14). In women ≥ 50, G3a/G3b rose to 11.3%/4.9% and G3-G4 exceeded men (17.6% vs 14.6%) despite lower A2-A3 odds (aOR 0.71, 95% CI 0.62-0.80), suggesting post-midlife eGFR-albuminuria decoupling. KDIGO 2024 eligibility in women ≥ 50: RASi 12.1%, SGLT2i 18.7%, nsMRA 3.6%, statins 35.2% (substantial opportunities even with A1-A2 albuminuria). In this primary care population, sex differences in CKD are strongly age-dependent: women are protected before midlife, but this advantage disappears beyond age 50 years, with convergence of CKD G3-G5 risk despite differences in albuminuria. These findings support sex- and menopause-aware CKD screening and guideline-directed renoprotective and cardioprotective therapy in older women even in the absence of overt albuminuria.
Parenthood fundamentally reshapes economic trajectories yet establishing causality remains methodologically challenging due to selection and timing endogeneity. This study introduces a novel identification strategy exploiting contraceptive failures as an exogenous source of variation in parenthood status. Using nationally representative survey data, I compare individuals who experienced contraceptive failures resulting in births against those using contraception who did not conceive. The findings reveal a striking gender paradox: while motherhood substantially reduces women's unconditional employment probability by approximately 20 per cent and higher education attainment by 5 per cent, fatherhood increases men's employment likelihood by 7 per cent and educational achievement by 11 per cent. These effects are most pronounced during children's first decade, with maternal employment penalties disappearing after age 10, though educational gaps persist. If the identifying assumptions are satisfied, this suggests that first unintended parenthood may not fully explain persistent long-term gender disparities, though cumulative fertility and anticipatory effects remain important candidates. This research introduces contraceptive failure as a credible new identification strategy, documenting bidirectional gender effects that amplify inequality. The results challenge conventional policy approaches by revealing that gender gaps arise not only from maternal penalties but also from paternal premiums.
This article examines Ukraine's Global Fund "Transition Plan" as a governance technology that reorganised time, responsibility, and uncertainty in HIV prevention, rather than as a policy instrument that simply succeeded or failed. Introduced in 2016 as a condition of continued donor support, the Plan promised a "gradual" shift from zero state financing of prevention to 80% by 2020. While the assessments concluded that Ukraine met-and even exceeded-its budgetary commitments, substantially less funding reached frontline services. We show how this gap was produced through performance-based spending, procurement rules, and audit procedures tied to pre-set coverage and service-volume targets that proved difficult to realise under punitive drug policy, repeated cycles of forced client mobility and disappearance, and broader precarity. Drawing on multi-sited qualitative fieldwork and policy analysis, we trace how donors, state bodies, and NGOs reproduced vertical governance through metrics, tenders, and accountability regimes. We situate these dynamics within a "double becoming" of Western and (post-)Soviet modernities, in which future-oriented targets produce (un)certainty while displacing attention from present constraints. The Plan thus appears simultaneously feasible, as an auditable system, and fantastic, as delivery depends on stabilising criminalised, mobile lives-producing an interpretive impasse between budgetary overfulfilment and service underdelivery. This, we argue, constitutes the Transition Plan as a broader condition, as a metaphor for post-Soviet transformation towards the "West".
Fully regressive melanoma is an exceedingly rare phenomenon characterized by the complete histopathologic disappearance of malignant melanocytes, replaced by fibrosis, melanophages, and lymphocytic infiltrates, without identifiable residual tumor cells. We report the case of a 71-year-old female who presented with a pigmented lesion of the right auricle, which was incidentally noted by her daughter. Clinical examination revealed a darkly pigmented, asymmetrical macule with retention of hair follicles, raising suspicion for a benign melanocytic nevus. Excisional biopsy revealed complete regression of a superficial spreading melanoma without measurable Breslow thickness or vertical growth phase. Immunohistochemical studies demonstrated positivity for melanocytic markers and a low proliferative index, while imaging with PET/computed tomography and MRI revealed no evidence of regional or distant metastasis. Given the absence of high-risk features, sentinel lymph node biopsy was not performed, and the patient underwent wide local excision with no residual malignancy identified. She remains disease-free under close clinical follow-up. This case highlights the diagnostic and management challenges associated with fully regressive melanoma and emphasizes the need for heightened clinical suspicion and individualized treatment strategies. Further research is required to better understand the prognostic significance and optimal follow-up protocols for this rare melanoma subtype.
This study investigates the regional accumulation of toxic, essential, and rare earth elements (REEs) in 42 human brain samples across neocortical, limbic, and subcortical regions. Using ICP-MS and multivariate frameworks, we demonstrate that elemental ratios (specifically Fe/Mg and Fe/Zn) provided stronger regional discrimination than absolute concentrations, with PCA explaining 51% versus 34% of variance, effectively capturing the brain's stoichiometric architecture. Mn and Fe exhibited the strongest regional gradients, with median concentrations in subcortical nuclei approximately two-fold higher than in the neocortex, consistent with DMT1-mediated transport and established tropism for dopaminergic structures. Elevated Mn in the limbic continuum supports a hybrid accumulation scenario combining systemic and olfactory pathways, while Fe enrichment in subcortical regions reflects its physiological role in dopamine metabolism rather than olfactory transport. Elevated Fe/Zn and Fe/Mg ratios in subcortical structures, driven by localised Fe surges rather than depletion of neuroprotective cofactors, suggest a relative weakening of antioxidant defense's and potential predisposition to ferroptotic neurodegeneration. Cd showed preferential accumulation in subcortical structures, consistent with Ca²⁺ mimicry-mediated neuronal entry and age-related blood-brain barrier degradation, with low limbic concentrations arguing against a dominant olfactory route for this element. Lanthanides accumulated as a unified geochemical block. 96% of their total variance was captured by a single principal component, with most REEs exhibiting identical significance levels (pBH = 0.0107). A spatial segregation was identified between light REEs enriched in subcortical nuclei via calcium channel mimicry and heavy REEs preferentially distributed in limbic structures, suggesting dual entry routes. The disappearance of regional differences in relative-profile space (CLR) points toward a non-selective lanthanide accumulation mechanism, potentially involving axonal pathways or vascular niches. The neocortex emerged as the most chemically distinct compartment, maintaining a unique elemental baseline compared to limbic and subcortical structures. These findings underscore the importance of anatomical stratification in neurotoxicological risk assessments, with particular relevance to the etiopathogenesis of neurodegenerative diseases associated with metal dyshomeostasis in the basal ganglia.
Graph neural networks (GNNs), which learn node representations via aggregating their neighbors, have shown superior performance and become the de facto efficient toolkit for analyzing and learning from data with structured properties. However, most existing GNNs are designed for static graphs and assume fixed graph structures and node sets. In many real-world applications, graphs evolve continuously over time-with nodes and edges appearing or disappearing-rendering static models insufficient for capturing these temporal dynamics. In this paper, we propose Evolving Graph Attention Networks (EGAT), a novel framework for dynamic graph representation learning. Specifically, EGAT leverages the anisotropic attention mechanism of Graph Attention Networks (GATs) to capture complex inter-node relationships. Crucially, the multi-head attention weights of the GAT are evolved over time via a recurrent neural network (RNN), enabling the model to adaptively adjust the importance of different neighbors as the graph topology and relational dynamics change. This weight-evolving paradigm couples the anisotropic attention mechanism of GATs with a recurrent subnetwork, enabling the joint modeling of topological evolution and temporal relational dynamics. Extensive experiments on benchmark datasets demonstrate that the proposed model consistently outperforms state-of-the-art baselines.
Idiopathic intracranial hypertension (IIH) classically presents with headache, papilledema, and visual disturbances. Psychiatric manifestations are rare and may obscure a timely diagnosis. A 23-year-old obese female with no prior psychiatric history presented with new-onset intrusive thoughts and compulsive finger-tapping rituals, leading to a diagnosis of obsessive-compulsive disorder (OCD). Despite treatment with high-dose SSRIs, antipsychotic augmentation, and cognitive-behavioural therapy for six months, she showed no improvement. She concurrently reported a refractory bitemporal headache, tinnitus, and transient visual obscurations. Examination revealed bilateral papilledema. MRI/MRV showed features of raised intracranial pressure (ICP) associated with right transverse sinus stenosis. Lumbar puncture (LP) confirmed an elevated opening pressure of 30 cm H₂O. Despite treatment with acetazolamide (2 g/day), she remained symptomatic. Venous sinus stenting was subsequently performed, restoing sinus caliber and reducing the pressure gradient. Within three months, her headache improved markedly, and her papilledema resolved. Remarkably, her obsessive thoughts and compulsive acts completely disappeared without psychiatric medication, with her Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score dropping from 20 to 5. This case illustrates IIH presenting with predominant psychiatric manifestations mimicking primary OCD. The dramatic resolution of compulsive symptoms following intracranial pressure normalization suggests a possible association between IIH and obsessive thoughts. Clinicians should maintain a high index of suspicion for IIH in atypical psychiatric presentations accompanied by headache, tinnitus, or visual symptoms; in such cases, routine fundoscopy is essential.
Controversy exists regarding the selection of the target temperature for patients with out-of-hospital cardiac arrest (OHCA). This study aims to identify the subgroups of patients who can benefit from targeted temperature management (TTM) at 33 °C. We retrospectively analyzed 282 OHCA patients, who were categorized based on the administration of 33 °C TTM and early mortality within 24 h of ICU admission. The median value was used to determine the cutoff for continuous variables, and patients were further divided into subgroups according to different variables; the outcomes were survival status and neurological function at discharge. Difference analysis, multivariate logistic regression (MLR), and propensity score matching (PSM) were applied to analyze the efficacy of different TTM regimens in each subgroup. Subgroup analysis showed that 33 °C TTM was associated with better survival only in patients without bystander CPR (OR [95%CI]: 3.41 [1.13, 10.31], P = 0.029), whereas this association disappeared after MLR and PSM adjustment. Among patients with an APACHE II score < 30, the Non-33 °C TTM group presented a more favorable neurological prognosis (χ²: OR [95%CI]: 0.34 [0.17, 0.70], P = 0.003; MLR: 0.29 [0.08, 0.96], P = 0.046). 33 °C TTM stable group was related to superior survival only in the APACHE II > 30 subgroup in MLR analysis (OR [95%CI]: 3.47 [1.09, 12.32], P = 0.042). After MLR and PSM adjustment, favorable neurological outcomes remained significantly higher in the Non-33 °C TTM stable group among patients with cardiac etiology (MLR: OR [95%CI]: 0.25 [0.06, 0.94], P = 0.046; PSM: 0.08 [0.01, 0.51], P = 0.017) and those with APACHE II < 30 (MLR: OR [95%CI]: 0.27 [0.07, 0.88], P = 0.034; PSM: 0.19 [0.04, 0.80], P = 0.029). 33 °C and Non-33 °C TTM strategies were associated with clinical outcomes in specific subgroups of OHCA patients, and further studies are warranted to clarify this association.
Visual attention is suppressed for targets that are located close to the attended location, but recovered for more distant targets, which is known as the location-based surround suppression. This study aimed to investigate whether the location-based surround suppression is modulated by the color salience or presentation time of features at these locations. Participants discriminated whether two targets on a circle were identical or different after one of them was cued. Low-salience with a short-time condition (i.e., baseline), low-salience with a long-time condition, and high-salience cue with a short-time condition were employed in Experiments 1-3. High-salience cue-targets with a long-time condition, no-cue control condition, and high-salience targets with a short-time condition were employed in Experiments 4-6. Discrimination accuracy gradually increased with increasing inter-target distance under the low-salience with short-time condition, indicating that nearby targets might fall within the cued target's suppressive surround, but distant targets might not. Not only accuracy but also reaction time evidence for surround suppression was found under the long-time condition or high-salience cue condition in Experiments 2-3, revealing that surround suppression is more pronounced under these two conditions. However, surround suppression disappeared once the high-salience targets were employed in Experiments 4-6, even under the long-time condition. These findings demonstrated that location-based surround suppression is dynamically modulated by the interaction of three factors: top-down control (cue salience), bottom-up competition (target salience), and availability of feedback-processing resources (stimulus presentation time).
Despite extensive study, how conscious and unconscious priming influence visual perception remains only partially understood. In this work, we examine their distinct effects across multiple experimental conditions within a binocular rivalry paradigm to provide a more comprehensive perspective on identity and category recognition. Participants were presented with word or image primes, followed by a name-picture verification task in which faces or animal bodies served as targets. Although conscious priming has been shown to facilitate identity recognition while interfering with category perception, the precise distinction between conscious and unconscious states, as well as the mechanisms underlying unconscious priming, requires further detailed analysis. Left-hemispheric processing was one of the influential factors in distinguishing conscious from unconscious priming effects. Interestingly, we observed a negative correlation between conscious and unconscious perception during identity recognition, highlighting the condition-dependent modulation of visual perception in the priming paradigm. From the regression analyses, awareness showed the strongest predictor of priming magnitude, with recognition level playing a secondary role. More broadly, our findings demonstrate that visual perception circuits are modulated condition-dependently, underscoring how awareness and trial context jointly shape recognition processes. Conscious priming facilitated identity but impaired category recognition.Unconscious priming lacked identity-category dissociation.Identity priming showed negative conscious-unconscious correlation.Right visual field effects distinguished awareness states.Awareness was the strongest predictor of priming magnitude. Our brains are constantly influenced by things we have just seen-even when we are not aware of seeing them. This phenomenon is called priming. In this study, we explored how visible (conscious) and invisible (unconscious) hints affect the way people recognize images. Participants viewed brief words or pictures before being asked to identify either a specific individual (for example, a particular dog breed or person) or a broader category (such as "dog" or "animal"). Sometimes these hints were clearly visible. Other times they were hidden from awareness using a special visual technique. We found that when people were consciously aware of the hint, it helped them recognize specific identities faster-but surprisingly, it made them slower at recognizing broader categories. In contrast, when the hint was invisible, this clear pattern disappeared. Even more interesting, for identity recognition, the effects of visible and invisible hints often moved in opposite directions. What helped in the conscious condition could hinder in the unconscious one. We also discovered that awareness itself was the most important factor shaping these effects- more important than whether the hint was a word or picture, or whether it appeared on the left or right side of the screen. Why does this matter? These findings show that conscious and unconscious influences on perception are not simply weaker or stronger versions of the same process-they work differently. Understanding how awareness shapes recognition may help us better understand attention, decision-making, advertising effects, and even clinical conditions where perception or awareness is altered.
Macro-thyrotropin (TSH) is a high molecular weight complex of TSH associated with apparently elevated levels of serum TSH, which can lead to an incorrect diagnosis of subclinical hypothyroidism. Given that levothyroxine (LT4) replacement is unnecessary in such cases, the accurate identification of macro-TSH based on clinical and laboratory findings is of particular importance. We aimed to determine the prevalence and clinical features of macro-TSH in patients with subclinical hypothyroidism evaluated after the introduction of TSH harmonization. Between August and November 2023, we included 1599 consecutive patients with subclinical hypothyroidism (TSH > 4.23 mIU/L with normal fT4 levels) who were either untreated or receiving LT4 replacement monotherapy. Polyethylene glycol (PEG) precipitation was performed in all cases. Patients with TSH recovery of <20% underwent further evaluation, including gel filtration chromatography under neutral and acidic conditions, protein G and Jacalin precipitation assays, and a comprehensive battery of interference tests. Four patients (0.25%) showed high molecular-weight TSH peaks (>150 kDa) under neutral conditions that disappeared under acidic conditions, with a shift to the native molecular weight (approximately 28 kDa), indicating the initial presence of macro-TSH. The TSH complex was detected in peaks corresponding to IgG, IgA, and IgM. These findings were verified using Protein G and Jacalin precipitation assays, with no evidence of assay interference. Reevaluation of TSH recovery following PEG precipitation showed substantial variation in two patients who had abundant monomeric TSH compared with the high-molecular complex. All four patients with macro-TSH had previously received LT4 therapy, which resulted in a modest reduction in TSH levels, with three of these patients testing positive for TgAb and/or TPOAb. Macro-TSH complexes comprise several immunoglobulin isotypes. In cases with low antibody-TSH binding affinity and positive antithyroid autoantibodies, TSH levels may fluctuate during the clinical course, thereby complicating diagnosis and management.
We tested the extent to which mothers' speech contributes to the transmission of family background inequality in education. In 894 families (93.1% White), representative of the full range of Britain's socioeconomic conditions, we quantified mothers' vocabulary sophistication, lexical diversity, and grammatical complexity from 10-min-long audio-recorded interviews. Mothers' vocabulary sophistication significantly predicted children's (49% males) cognition, literacy, and educational achievement from ages 5 to 12 years, accounting for 2%-5% of the variance. After adjusting for mothers' education and household income, these effects reduced to 1% and 2% or became nonsignificant. Our findings suggest vocabulary sophistication contributes only modestly to the transmission of family background inequality in education. Research has shown that the way mothers talk to their children before they start school may play a role in passing on educational inequalities. The longer-term impact of mothers' speech beyond the early years is not well understood. Using interviews with 894 mothers from a wide range of socioeconomic backgrounds, we examined whether differences in mothers' vocabulary and grammar are linked to children's outcomes at school. Children whose mothers used more sophisticated vocabulary showed small advantages in cognitive ability and reading between ages 5 and 10. However, when mothers' education and household income were taken into account, most of these links became weaker or disappeared. Overall, mothers' education and household income had a stronger long-term influence on children's educational outcomes.
Chaotic quantum systems at finite entropy density are expected to act as their own heat baths, rapidly dephasing local quantum superpositions. We argue that in fact this dephasing is generically subexponential in one-dimensional systems with conservation laws: all local correlation functions decay as exp[-O(t^{α})] with 0≤α≤2/3, even when the operators are orthogonal to all hydrodynamic modes. The mechanism is diffusion-limited dephasing, in which rare low-entropy regions ("voids") protect quantum coherences. This intrinsically quantum effect lies beyond standard hydrodynamics and disappears under extrinsic dephasing. In random charge-conserving circuits we find α=1/2, while in generic translation-invariant Floquet systems we bound α≤2/3. Our arguments are general, subject principally to the assumption that thermal fluctuations can create regions of zero entropy density. In systems with energy conservation, this assumption is automatically satisfied because of the third law of thermodynamics.
This study was designed to examine the metaphorical perceptions and meaning-making schemas of hemodialysis patients regarding the concept of death. The study, designed qualitatively through metaphor analysis, included 38 hemodialysis patients. Data were collected using forms on semi-structured interviews employing writing and drawing techniques to explore perceptions of death. The data were analyzed using content analysis. It was determined that hemodialysis patients participating in the study produced four metaphors (The end of life and reaching union, Nightmare and despair, Sense of disappearance and emptiness, and The journey of life) each using the writing technique and drawing technique. The study revealed that hemodialysis patients interpret death within the framework of complex cognitive schemas, intense anxiety and multidimensional meanings. The findings indicate that this process of interpretation is strongly shaped by religious and spiritual interpretations. In this regard, recognizing and strengthening patients' psychological, social, and spiritual coping resources is of great importance. Psychosocial nursing interventions based on metaphors, person centered care, and spiritual care components can make meaningful contributions to reducing death-related anxiety and strengthening emotional well-being.
Bulk formamidinium lead triiodide (FAPbI3) films host spontaneously formed quantum-confined (QC) domains, but their structural origin remains unclear. Using controlled material degradation in humid air as a dynamic lattice perturbation, we track the evolution of QC features in thin-film absorption of FAPbI3. With aging, above-bandgap QC features redshift and diminish, indicating weakened electronic confinement. Concurrently, X-ray diffraction reveals that breakdown of α-phase connectivity coincides with the loss of short-range higher-order hexagonal (nH, n > 2) polytypes as the material converts to the 2H δ-phase. Such polytypic nanodomains may generate peaked absorption features by forming higher-energy barriers confining charge carriers within α-FAPbI3 or by introducing distinct electronic states associated with mixed octahedral connectivity. Progressive degradation dismantles this framework, causing the disappearance of the QC features. Our results identify the structural motifs underpinning QC effects and propose that controlling higher-order (n > 2) hexagonal polytypes offers a route to tuning quantum confinement in FAPbI3 films.
Achalasia is a rare primary esophageal motility disorder. While laparoscopic Heller myotomy (LHM) is a well-established treatment worldwide, no studies to date have evaluated its long-term outcomes and risk factors for failure in low- and middle-income countries (LMICs). In our context, peroral endoscopic myotomy (POEM) remains uncommon, and surgery is still the first-line treatment. This study aims to evaluate the functional and symptomatic outcomes of laparoscopic Heller myotomy (LHM), identify risk factors associated with surgical failure, and highlight the benefits of concomitant anti-reflux procedures in reducing the incidence of gastroesophageal reflux. We conducted a retrospective analysis of 55 consecutive patients who underwent LHM with or without an anti-reflux system (ARS) between July 2000 and December 2022. Clinical success was defined as the resolution of dysphagia with a concomitant improvement in the Eckardt score, corroborated by objective assessments including lower esophageal sphincter (LES) pressure measurements and 24-hour pH-metry. Iatrogenic reflux was diagnosed based on clinical symptoms and confirmed through esophageal pH-metric evaluation. Potential risk factors contributing to treatment failure were systematically analyzed. Dysphagia (98.2%) and weight loss (74.5%) were the predominant symptoms. In our series, two conversions were reported (3.6%) following esophageal perforation. Nineteen patients (34.5%) had undergone ARS, with 10 of DOR type (18.2%) and 9 of Toupet/Nissen type (16.4%). With a mean follow-up of 24.47 months, dysphagia had disappeared in 51 (92.8%) and the mean Eckardt score was improved by 0.92 (+/- 1.25) vs. 5.46 (+/- 1.77) with P=<0.05. All patients with persistent dysphagia had lost weight preoperatively (P=0.05). The absence of an anti-reflux system was associated with more gastro-esophageal reflux disease (16.7% vs. 5.2%, P=0.181) and more esophageal exposure to gastric acid (9.1% vs. 16.4%, P=0.224). ARS, whether Dor or Toupet, were effective in preventing postoperative reflux. In our LMIC setting, LHM remains the gold standard for achalasia treatment given the limited availability of POEM. When combined with ARS, it provides durable symptom control, prevents reflux, and maintains good functional results. Preoperative weight loss may predict poorer postoperative outcomes.
Lithium-rich antifluorite oxides formed by metal ion substitution in Li2O are highly promising cathode prelithiation materials. Understanding the connection between their structure and performance is crucial for this type of material. In this paper, by forming solid solutions of α/β-Li5AlO4 and Li5FeO4, a group of continuous solid solutions, α-Li5FexAl1-xO4, and another group of phase transition solid solutions, β-Li5FexAl1-xO4, which underwent a phase transition at x = 0.5 were obtained, respectively. Changes in the local and electronic structures of the FeO4 polyhedra were observed in the α-phase solid solution, and the decrease in electrochemical activity led to a linear attenuation of battery capacity. The structural changes after the phase transition of the β-phase solid solution led to the enhancement of the Li-Fe interaction, resulting in the disappearance of the delithiation performance within the working voltage. This study established a direct connection among local coordination structure, electronic structure, and electrochemical activity in lithium-rich antifluorite with abundant lithium content, providing a key theoretical basis for the rational design of high-performance prelithiation agents.