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We present a dataset of 1,119 radiocarbon dates and their contexts for Oaxaca, Mexico, a best effort to include all published dates, plus hundreds of unpublished samples. We illustrate its potential and limitations with five examples: (1) dated stratigraphy in stream cutbanks show how aggradation, downcutting, and stability responded to global climate and human activities; (2) 14C samples from Late/Terminal Formative contexts allow interregional comparisons of temple and palace construction, use, and abandonment; (3) new 14C dates provide better understanding of events during the Late Classic/Epiclassic, a problematic time in the ceramic chronology; (4) individual Classic/Postclassic residential contexts had long durations—several hundred years; and (5) model constraints from other data permit refinement at times of calibration curve deviation, as during AD 1400–1600. We recommend further chronological refinement with best-practice standards, new samples, existing collections, and statistical modeling.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
Cardiac surgery-associated acute kidney injury (CS-AKI) and fluid overload (FO) are common among neonates who undergo cardiopulmonary bypass, and increase mortality risk. Current diagnostic criteria may delay diagnosis. Thus, there is a need to identify urine biomarkers that permit earlier and more accurate diagnosis.
Methods:
This single-centre ancillary prospective cohort study describes age- and disease-specific ranges of 14 urine biomarkers at perioperative time points and explores associations with CS-AKI and FO. Neonates (≤28 days) undergoing cardiac surgery were included. Preterm neonates or those who had pre-operative acute kidney injury were excluded. Urine biomarkers were measured pre-operatively, at 0 to < 8 hours after surgery, and at 8 to 24 hours after surgery. Exploratory outcomes included CS-AKI, defined by the modified Kidney Disease Improving Global Outcomes criteria, and>10% FO, both measured at 48 hours after surgery.
Results:
Overall, α-glutathione S-transferase, β-2 microglobulin, albumin, cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, uromodulin, clusterin, and vascular endothelial growth factor concentrations peaked in the early post-operative period; over the sampling period, kidney injury molecule-1 increased and trefoil factor-3 decreased. In the early post-operative period, β-2 microglobulin and α-glutathione S-transferase were higher in neonates who developed CS-AKI; and clusterin, cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, and α-glutathione S-transferase were higher in neonates who developed FO.
Conclusion:
In a small, single-centre cohort, age- and disease-specific urine biomarker concentrations are described. These data identify typical trends and will inform future studies.
Long-acting injectable antipsychotics (LAIs) reduce relapses in schizophrenia; however, most healthcare professionals (HCPs) reserve LAIs for nonadherence to oral antipsychotics (OAs) or severe disease.
Methods
US HCPs were surveyed regarding attitudes and perceptions toward LAIs for schizophrenia and LAI selection preferences. Respondents were grouped by LAI use (high [≥31% of patients using LAIs], low [≤14% using LAIs]; mid not analyzed) and archetype based on response to, “Which of the following best fits the current way you view your use of [LAIs] for your patients with schizophrenia?” (see responses below).
Results
Respondents (106 high, 130 low LAI use) were distributed across early LAI use (n=123), severity-reserved (n=88), adherence-reserved (n=113), and LAI-hesitant (n=56) archetypes.
Across all groups, HCPs estimated OA nonadherence in their practice (21%– 32%) to be lower than for patients nationwide (50%– 56%). Overall, 27% were dissatisfied with their LAI:OA use ratio, most thinking their OA use was too high. In all groups, side effects/tolerability was ranked as most important when choosing an LAI and “preference for the molecule” was ranked least important. Overall, 71%– 77% of HCPs were somewhat/much more likely to use a particular LAI based on multiple injection site options, small/on par needle, and price, and 63%– 82% of HCPs were somewhat/much more likely to select an LAI dosed once monthly or less often compared with an LAI dosed once every 2 weeks (8%). HCPs with high LAI use or early LAI use archetype were more likely to disagree that managing patients with schizophrenia increased their stress (64% and 63% vs 27%-45%, P<.05 each) and/or left them feeling “burned out” (77% and 79% vs 50%– 64%, P<.05 each).
Compared with other groups, greater proportions with high LAI use or early LAI use archetype consistently read new LAI publications (18% and 19% vs 0%– 5%, P<.01) and were confident in key aspects of LAI treatment (ie, dosing, managing side effects, access; 67%– 74% and 59%– 70% vs 11%– 57%, P<.05 each).
HCPs with low LAI use estimated the proportion of patients who initially refuse LAIs to be higher (mean, 55%) than those with low LAI use (44%, P<.01); there were no differences among archetypes (49%– 54%). HCPs with high LAI use or early LAI use archetype were more likely to “use any means necessary to ensure that a patient is on an LAI” vs other groups (44% and 51% vs 5%– 22%, P<.01 each) or had used guardianship to assist with treatment (70% and 69% vs 32%– 56%, P<.05 each); greater proportions with high LAI use or early LAI use archetype strongly agreed it was “worth [their] time to resolve issues with the insurance company” (42% and 45% vs 16%– 30%, P<.05 each) and were confident they would be able to do so (23% and 20% vs 2%– 11%, P<.05 each). Greater proportions of HCPs with early LAI use archetype vs the severity-reserved archetype strongly agreed that they attempt to determine the patient’s/caregiver’s preferred role before involving them (43% vs 27%, P<.05) and encourage them to participate (72% vs 57%, P<.05) in shared decision-making.
Conclusions
Comparing HCPs with high LAI use or early LAI use archetype vs other groups, multiple factors (eg, attitudes, preferences, training, knowledge base) combine to influence LAI use. These results highlight considerations for developing educational materials to increase LAI use in this population.
Large datasets, combined with modeling techniques, provide a quantitative way to estimate when known archaeological sites will be impacted by climatological changes. With over 4,000 archaeological sites recorded on the coast of Georgia, USA, the state provides an ideal opportunity to compare methods. Here, we compare the popular passive “bathtub” modeling with the dynamic Sea Level Affecting Marshes Model (SLAMM) combined with the Marshes Equilibrium Model (MEM). The goal of this effort is to evaluate prior modeling and test the benefits of more detailed ecological modeling in assessing site loss. Our findings indicate that although rough counts of archaeological sites destroyed by sea-level rise (SLR) are similar in all approaches, using the latter two methods provides critical information needed in prioritizing site studies and documentation before irrevocable damages occur. Our results indicate that within the next 80 years, approximately 40% of Georgia's coastal sites will undergo a loss of archaeological context due to wetlands shifting from dry ecological zones to transitional marshlands or submerged estuaries and swamps.
Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.
Method:
Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.
Results:
Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.
Conclusions:
Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.
Key learning aims
(1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.
(2) To understand the facilitators of and barriers to ACT for plwMND.
(3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.
The figure of Anthony Comstock may seem like an odd historical relic: a repressed, puritanical, anti-sex reformer from a bygone past. And yet, because his namesake act has been revived as a potential strategy for limiting access to reproductive healthcare, Comstock is no joke. Today, some Americans see the Comstock Act, passed by Congress in 1873, as a pathway to banning abortion and other reproductive care, effectively jettisoning any need for new Supreme Court abortion rulings or congressional legislation. As scholars of the Gilded Age and Progressive Era, we are uniquely situated to intervene in this dialogue and ensure that contemporary conversations are grounded in historical context. We present this forum not as an exhaustive account of the Comstock Act and its architect, but as aopportunity to highlight the context in which this law, which holds so much potential relevance for our present, was created, enacted, enforced, and challenged. We hope this forum will stimulate further scholarly and public conversations around the nation’s long history of regulating reproductive rights and how that history became entangled with other social anxieties.
The psychometric rigor of unsupervised, smartphone-based assessments and factors that impact remote protocol engagement is critical to evaluate prior to the use of such methods in clinical contexts. We evaluated the validity of a high-frequency, smartphone-based cognitive assessment protocol, including examining convergence and divergence with standard cognitive tests, and investigating factors that may impact adherence and performance (i.e., time of day and anticipated receipt of feedback vs. no feedback).
Methods:
Cognitively unimpaired participants (N = 120, Mage = 68.8, 68.3% female, 87% White, Meducation = 16.5 years) completed 8 consecutive days of the Mobile Monitoring of Cognitive Change (M2C2), a mobile app-based testing platform, with brief morning, afternoon, and evening sessions. Tasks included measures of working memory, processing speed, and episodic memory. Traditional neuropsychological assessments included measures from the Preclinical Alzheimer’s Cognitive Composite battery.
Results:
Findings showed overall high compliance (89.3%) across M2C2 sessions. Average compliance by time of day ranged from 90.2% for morning sessions, to 77.9% for afternoon sessions, and 84.4% for evening sessions. There was evidence of faster reaction time and among participants who expected to receive performance feedback. We observed excellent convergent and divergent validity in our comparison of M2C2 tasks and traditional neuropsychological assessments.
Conclusions:
This study supports the validity and reliability of self-administered, high-frequency cognitive assessment via smartphones in older adults. Insights into factors affecting adherence, performance, and protocol implementation are discussed.
Advanced biopreservation technologies using subzero approaches such as supercooling, partial freezing, and vitrification with reanimating techniques including nanoparticle infusion and laser rewarming are rapidly emerging as technologies with potential to radically disrupt biomedicine, research, aquaculture, and conservation. These technologies could pause biological time and facilitate large-scale banking of biomedical products including organs, tissues, and cell therapies.
Circular shell rings along the South Atlantic coast of the United States are vestiges of the earliest sedentary villages in North America, dating to 4500–3000 BP. However, little is known about when Indigenous communities began constructing these shell-ring villages. This article presents data from the Hokfv-Mocvse Shell Ring on Ossabaw Island, Georgia. Although shell rings are often associated with the earliest ceramics in North America, no ceramics were encountered in our excavations at Hokfv-Mocvse, and the only materials recovered were projectile points similar to points found over 300 km inland. Bayesian modeling of radiocarbon dates indicates that the ring was occupied between 5090 and 4735 cal BP (95% confidence), making it the earliest dated shell ring in the region. Additionally, shell geochemistry and oyster paleobiology data suggest that inhabitants were living at the ring year-round and had established institutions at that time to manage oyster fisheries sustainably. Hokfv-Mocvse therefore provides evidence for Indigenous people settling in year-round villages and adapting to coastal environments in the region centuries before the adoption of pottery. The establishment of villages marks a visible archaeological shift toward settling down and occupying island ecosystems on a more permanent basis and in larger numbers than ever before in the region.
Fructose-containing sugars can exaggerate postprandial lipaemia and stimulate hepatic de novo lipogenesis (DNL) when compared to glucose-based carbohydrates(1). Galactose has recently been shown to increase postprandial lipaemia compared to glucose(2), but mechanisms remain uncharacterised. The aim of this study was to assess the effect and mechanisms of lactose-induced lipaemia.
Twenty-four non-obese adults (12 male and 12 female) completed three trials in a randomised, crossover design (28 ± 7-day washout). During trials, participants consumed test drinks containing 50 g fat with 100 g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was galactose-containing carbohydrate (lactose) and the active comparator was fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed by the 2H2O method and [U-13C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath 2H and 13C enrichments. Data were converted into incremental under the curve (iAUC) and were checked for normality by visual inspection of residuals. Differences between trials were assessed by one-way ANOVA. Where a main effect of trial was detected, post- hoc t-tests were performed to determine which trials differed from lactose according to the principle of closed-loop testing.
The plasma triacylglycerol iAUC (mean ± SD) in response to maltodextrin was 51 ± 68 mmol/L*360 min. Following lactose ingestion, plasma triacylglycerol iAUC increased to 98 ± 88 mmol/L*360 min (p<0.001 vs maltodextrin), which was comparable to sucrose [90 ± 95 mmol/L*360 min (p=0.41 vs lactose)]. Hepatic DNL in response to maltodextrin was 6.6 ± 3.0%. Following ingestion of lactose, hepatic DNL increased to 12.4 ± 6.9% (p=0.02 vs maltodextrin), which was comparable to sucrose [12.2 ± 6.9% (p=0.96 vs lactose)]. Exhaled 13CO2 in response to maltodextrin was 10.4 ± 4.1 mmol/kgFFM*360 min. Following ingestion of lactose, exhaled 13CO2 was 8.8 ± 4.9 mmol/kgFFM*360 min (p=0.09 vs maltodextrin), which was lower than sucrose [11.1 ± 3.9 mmol/kgFFM*360 min (p=0.01 vs lactose)].
These data are consistent with the hypothesis that hepatic de novo lipogenesis contributes to both lactose and sucrose-induced lipaemia and provide a rationale to investigate the longer-term effects of lactose and sucrose on metabolism.
The oxidative power of a smectite can be measured quantitatively by oxidation of hydro-quinone to p-benzoquinone in a clay slurry. Oxidation takes place in the presence of O2 (air) but not N2 unless Fe3+ or Cu2+ are the exchangeable cations. This study examined 26 smectite samples with varying compositions and processing. The oxidative power increases with decreasing Li-fixation and increasing cation exchange capacity. Li-fixation does not depend upon the tetrahedral Al. The cation exchange capacity can decrease markedly by mere storage in water.
The oxidation proceeds principally on the surface by adsorbed oxygen molecules or radicals. A mechanism is proposed. With Fe3+ or Cu2+ present, even under N2, oxidation occurs via electron transfer. With smectites containing Fe2+, both the Fe and the hydroquinone are oxidized in the same reaction.
These studies concern the catalytic activity of clays on amino acids, particularly tyrosine. Polyhydric phenols were included to help understand the tyrosine reactions.
Below pH 3, tyrosine is adsorbed on clay minerals by cation exchange. Above pH 3, oxidative degradation of tyrosine occurs, the L-isomer altering more rapidly. The rate of alteration depends upon the particular clay mineral, surface modifications such as polyphosphate treatment, heating, and the presence of copper, aluminium, and mercury. A free radical mechanism is proposed for the alteration.
The absorption of biologically important purines, pyrimidines, and nucleosides by Li-, Na-, Mg-, and Ca-montmorillonite has been studied in aqueous solutions over a range of pH values 2–12. The initial organic concentrations were about 1 m.molar. The ratio clay to organic compounds was such that only up to 25 per cent of the exchange capacity could be saturated by organic cations, but, depending on conditions, up to 100 per cent of the available organic material was absorbed. Of the nineteen compounds studied, only thymine, uracil, and their nucleosides were not absorbed under the experimental conditions. Absorption occurs primarily as a cation exchange reaction under acid conditions and varies with the basicity of the compounds, their aromatic or non-aromatic character, and the possible extent of their van der Waals interaction with the silicate layers. Nucleosides generally are less strongly absorbed than their purines or pyrimidines because their non-planar structure permits less van der Waals interaction; their absorption is influenced by the differences in swelling behavior of montmorillonite with mono- and divalent cations.
Absorptions of purine and pyrimidine derivatives by Co- and Ni- montmorillonite at pH < 6 and by Cu-montmorillonite at pH < 3 are similar to their absorption by Ca-montmorillonite and take place primarily by a cation exchange process. In the weakly acidic to weakly alkaline range, absorption is due to complex formation with the inorganic cations, and decrease in the order Cu ≫ Ni > Co ≫ Ca. Adenine, 7-methyladenine, hypoxanthine, and purine are strongly absorbed, 9-methyladenine, 6-chloropurine, and cytosine are weakly absorbed, and thymine and uracil are not absorbed. At pH < 5, the nucleosides are absorbed by Co-, Ni-, and Cu-montmorillonite in approximately the same manner as by Ca-montmorillonite, but at pH > 6 their absorptions decrease in the order Cu ≫ Ni > Co > Ca. Fe(III)-montmorillonite behaves quite differently from the other mont-morillonites studied. With purines and pyrimidines, there is strong absorption from pH 3 to pH 7–8; with the nucleosides, the absorption varies considerably with the compounds considered decreasing in the order adenosine > cytidine ≫ guanosine ≫ inosine.
Quantitative analysis of clay minerals by X-ray powder diffraction requires oriented clays in order to increase detection limits of the analyses. This is achieved commonly either by smear or sedimentation techniques; however, these techniques can lead to poor analytical precision when used with an internal standard because they often produce non-homogeneous internal standard—clay mineral mixtures. Compaction of bulk shale material at 8000 psi in an hydraulic press produces preferred orientations comparable to that produced by smear or sedimentation. When used with a suitable platy internal standard which provides an estimate of clay mineral preferred orientation, excellent analytical precision is achieved routinely. Several lines of experimental evidence indicate that 1–5 µm MoS2 is an ideal orienting internal standard for use with compaction mounts.
Members of many racial and ethnic population subgroups are underrepresented in clinical trials and research. We present perspectives on barriers and facilitators to study participation gathered from Hispanic participants in a population-based genetic screening study.
Methods:
Seven focus groups (five in English and two in Spanish) were conducted with self-identified Hispanic participants of the Healthy Oregon Project (HOP), a large population-based cohort of adults residing in Oregon. HOP study participants complete surveys about cancer and chronic disease risks with the option to donate a saliva sample for no-cost genetic risk screening for inherited disorders. HOP invited Hispanic participants via email to join a focus group about their experiences. Focus groups, generally lasting 60–90 minutes, occurred in person and virtually. Notes were coded and content-analyzed.
Findings:
49 Hispanic adults participated in the focus groups (37 women; 9 men; 3 non-binary people). Identified facilitators for HOP study participation were trust in the academic medical center leading the study, having a family member who was impacted by cancer, and receiving free genetic screening. Identified barriers were difficulty completing the family history survey, lack of understanding or familiarity with research, immigration status, and navigating technology challenges. Recommendations to improve recruitment of Hispanic populations included promoting the study at community events, clinics, or schools, simplifying the consenting process and providing patient-focused videos to demonstrate study tasks, providing real-time sample tracking, and offering monetary incentives.
Discussion:
Our findings can inform strategies for bolstering recruitment of Hispanic adults in biomedical research studies.
Tetrathyridia of Mesocestoides corti were cultured in vitro in a diphasic medium consisting of a liquid medium (CMRL Sigma) and a thixotropic nutrient gel (Oxoid). Tests demonstrated that a 50% medium/gel mixture produced optimum conditions for the survival and development of tetrathyridia. Established anthelminthic drugs were inoculated into the gel which demonstrated that this system can be used for preliminary anthelminthic drug screening. The development and survival of the tetrathyridia were influenced by the addition of pepsin, trypsin and liver peptone to the culture media. The development and maturation of proglottids were observed in addition to asexual reproduction by the process of budding. Tetrathyridia maintained in vitro and reinfected into both mouse and rat hosts retained their viability.