To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Mental health issues are prevalent among children and young people (CYP) with chronic conditions like epilepsy, yet few access evidence-based psychological therapies. Evidence from the Mental Health Intervention for Children with Epilepsy (MICE) trial supports the effectiveness of a personalised modular psychological intervention, but cost-effectiveness is unknown.
Aims
To assess the cost-effectiveness of the MICE intervention compared with assessment-enhanced usual care at 12-months follow-up, taking a health and social care perspective.
Method
We conducted a within-trial economic evaluation. Outcomes were the Strengths and Difficulties Questionnaire (SDQ; primary) and quality-adjusted life years (QALYs; secondary) for CYP, caregivers, and CYP and caregivers combined. Sensitivity analyses examined missing data and intervention-costing assumptions.
Results
Cost-effectiveness results for the SDQ indicated that MICE had a higher probability of being cost-effective compared with control at a willingness to pay ≥£368 per unit improvement. For QALYs, MICE had a lower probability of being cost-effective for CYP compared with control (35 to 42%) across the £20 000–£30 000 per QALY threshold range. However, at the upper threshold this finding was reversed in sensitivity analyses with missing data imputed (45 to 58%) and with MICE costed at 75%, assuming the intervention partly substituted standard services (46 to 55%). Furthermore, MICE had a higher probability of being cost-effective for caregiver QALYs (52 to 63%) and combined CYP and caregiver QALYs (62 to 75%).
Conclusions
MICE appears to be cost-effective compared with assessment-enhanced usual care when considering QALYs for CYP and caregivers combined, though uncertainty exists across willingness-to-pay thresholds.
Sorgoleone, an allelochemical exuded from root hairs of grain sorghum [Sorghum bicolor (L.) Moench], has proven herbicidal activity on several weeds and crops. Due to its hydrophobic nature and affinity for organic matter, sorgoleone can persist in the soil for a long period. Although sorghum residues are beneficial for weed suppression, growers in the southeastern United States have raised concerns that these residues may negatively affect wheat (Triticum aestivum L.) emergence in double-crop systems. Two independent laboratory studies were conducted to evaluate sorgoleone activity: (1) weed species/wheat variety study, which included four weed species, Italian ryegrass [Lolium perenne L. ssp. multiflorum (Lam.) Husnot], large crabgrass [Digitaria sanguinalis (L.) Scop.], sicklepod [Senna obtusifolia (L.) Irwin & Barneby], and velvetleaf [Abutilon theophrasti Medik.], and two wheat varieties, ‘USG3251’ and ‘Shirley’; and (2) wheat variety and group study, which included a total of 20 varieties distributed in four wheat groups. In both studies, sorgoleone was applied at 0.025, 0.05, 0.10, 0.15, 0.20, and 0.30 g L−1 to seeds grown in petri dishes under laboratory conditions. In Study 1, sorgoleone activity had a stronger effect on grass weeds than on broadleaf weeds. Lolium perenne ssp. multiflorum was the most susceptible weed, showing 77% growth reduction at 0.3 g L−1 of sorgoleone. At the same concentration, D. sanguinalis showed the second-highest response, with a 32% growth reduction, followed by A. theophrasti and S. obtusifolia, with reductions of 23% and 20%, respectively. No effect of sorgoleone was observed on wheat varieties. In Study 2, growth reduction was only observed for six wheat varieties at the highest sorgoleone concentrations. Furthermore, in between group comparisons, Hard Red wheat presented higher response to sorgoleone. These findings demonstrate strong herbicidal activity of sorgoleone on grass weeds, particularly L. perenne ssp. multiflorum, while having minimal effects on most wheat varieties.
Liberia (West Africa) has an extensive (co)burden of urogenital and intestinal schistosomiasis; each largely restricted to more inland areas. Where urogenital schistosomiasis is endemic, as both disease surveillance and case management are nascent, many women may unknowingly be living with Female Genital Schistosomiasis (FGS). Using a recently developed FGS score card, we appraised FGS score card valuations with point-of-care gynaecological and molecular parasitological evaluations as undertaken within typical primary care settings of four Liberian counties. A total of 400 women, 100 participants from each of four endemic inland counties, underwent a cursory gynaecological examination using a speculum for visible FGS lesions, undertaken by a midwife, and provided a urine sample that was examined by centrifugation with microscopy for Schistosoma ova. Urine-sediments in ethanol were later analysed with a high-resolution melt (HRM) real-time (rt) PCR assay to screen for Schistosoma genetic markers. Using a combination of clinical and parasitological information, overall prevalence of UGS and FGS was <10% and a single case of putative FGS-associated co-infection with Schistosoma mansoni was observed. Participant interviews with the FGS score cards provided an insight into at-risk lifestyle and environmental factors, e.g. women who fished regularly were more likely to present with FGS whereas those who lived > 15 km from a local river were less likely to present with FGS. In this resource-poor setting of Liberia, active surveillance for FGS with either clinical or parasitological methods remains challenging such that sole future use of the FGS score card is most pragmatic for primary care.
To determine the local applicability of 2021 American Academy for the Study of Liver Diseases spontaneous bacterial peritonitis (SBP) treatment guidelines by evaluating the microbiology and clinical outcomes of SBP cases in an academic health system.
Design:
Retrospective cohort study.
Setting:
Five-hospital academic health system.
Patients:
Hospitalized adult patients with SBP.
Methods:
This study involved 2 components. First, patients meeting inclusion criteria with peritoneal fluid cultures positive for a pathogen were included in the culture-positive group. Antibiotic susceptibilities were analyzed for these patients. Second, remaining culture-negative patients were randomly selected and sequentially evaluated until the culture-negative and culture-positive groups were approximately the same size. Clinical data for all patients were evaluated based on empiric antibiotics received.
Results:
Forty-nine patients with culture-positive SBP and 48 patients with culture-negative SBP were included. Eight (16%) positive cultures contained TGC-nonsusceptible organisms. Patients receiving empiric third-generation cephalosporin (TGC) monotherapy had similar clinical outcomes as patients receiving empiric broad-spectrum therapy, including similar 30-day mortality (36% vs 38%; P = 1.00), 90-day mortality (55% vs 55%; P = 1.00), and median duration of hospitalization (6.5 d vs 8 d; P = .25). ICU admission, recent hospitalization, and nosocomial infection were not associated with TGC-nonsusceptible pathogen isolation in a univariate logistic regression analysis.
Conclusions:
Within our health system, 16% of isolates in culture-positive SBP patients were nonsusceptible to TGCs. No statistically significant difference was detected in clinical outcomes in patients receiving TGC or broader-spectrum antimicrobial therapy.
In sub-Saharan Africa’s endemic areas for urogenital schistosomiasis, male genital schistosomiasis (MGS) can cause significant morbidity. As part of the Hybridization in UroGenital Schistosomiasis investigation, an MGS sub-study examined a cohort of adult men over a calendar year to better ascertain general infection dynamics and putative zoonotic schistosome transmission. During follow-up, demographic, health and socio-economic data were collected through individual questionnaire interviews. Collected urine and semen were analysed using urine filtration, urine and semen microscopy and molecular DNA analyses of semen. Ten participants with reported MGS-associated symptoms had Schistosoma eggs in their urine and semen at 6-month follow-up, with seven at 12 months. Ten out of 11 participants with Schistosoma haematobium eggs on semen microscopy at baseline had persistent infection at 6-month follow-up, together with 6 new participants, giving an MGS prevalence of 84·2% (n = 19). Two also had Schistosoma mattheei eggs co-infection. Four of the 13 participants at 12-month follow-up had S. haematobium eggs in their semen which were persistent at all the time points. Using semen PCR, 14 participants (73·7%) had Schistosoma infection at 6 months, with only 2 participants being infected for first time. Upon DNA analysis, three participants also had hybrid co-infection at this time point. At 12 months, only 6 participants had Schistosoma infection with no hybrids detected. In summary, like S. haematobium and despite praziquantel treatment, both zoonotic and hybrid schistosomes can continue to cause MGS, which pose a further tangible challenge in future management and control measures.
Some psychotic experiences in the general population show associations with higher schizophrenia and other mental health-related polygenic risk scores (PRSs), but studies have not usually included interviewer-rated positive, negative and disorganised dimensions, which show distinct associations in clinical samples.
Aims
To investigate associations of these psychotic experience dimensions primarily with schizophrenia PRS and, secondarily, with other relevant PRSs.
Method
Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort participants were assessed for positive, negative and disorganised psychotic experience dimensions from interviews, and for self-rated negative symptoms, at 24 years of age. Regression models were used to investigate associations between psychotic experience dimensions and schizophrenia and other PRSs (2500+ participants for each analysis).
Results
Against expectation, none of the positive, negative or disorganised dimensions was associated with schizophrenia PRS. In secondary analysis, self-rated negative symptoms were associated with higher depression (β = 0.10 [95% CI 0.06–0.15]), anxiety (β = 0.09 [95% CI 0.04–0.13]), neuroticism (β = 0.11 [95% CI 0.06–0.15]) and autism (β = 0.09 [95% CI 0.05–0.13]) PRSs (all P < 0.001); and first-rank delusions were nominally associated with higher schizophrenia PRS (odds ratio 7.35 [95% CI 2.10–25.77], P = 0.002), although these experiences/symptoms were rare.
Conclusions
Positive, negative and disorganised psychotic experiences are probably not strongly associated with polygenic liability to schizophrenia in this general population cohort of young adults. Self-rated negative symptoms may indicate social withdrawal/low motivation due to higher polygenic liability to affective disorders or autism, and first-rank delusions may indicate higher polygenic liability to schizophrenia, but these findings require independent confirmation.
Urogenital schistosomiasis (UGS) caused by zoonotic or hybrid schistosome infection(s) is an emerging public health concern in Malawi, and we describe a 1-year clinical sub-study with 3 inspection time points for female genital schistosomiasis (FGS) upon selecting 86 women with proven UGS. This sub-study was set within a broader 2-year longitudinal ‘Hybridization in UroGenital Schistosomiasis (HUGS)’ investigation. A detailed cervicovaginal examination with a portable colposcope was conducted, examining cervicovaginal lavage (CVL), cervical swab, cervical biopsy and urine with traditional parasitological and molecular diagnostic methods. At baseline, overt FGS by colposcopy was 72.1%, 64.3% by CVL real-time PCR and 51.2% by both colposcopy and CVL-PCR, noting urine-microscopy could often be negative. Human papillomavirus was detected in 31.0% of the cervical swabs, with 8.3% women also FGS positive by colposcopy and real-time PCR. Over the year, FGS prevalence by colposcopy increased by 32.7% during the study to 84.6%, homogenous yellow and grainy sandy patches being very common in the youngest 18–25 age group, where 51.9% were positive. FGS appears widespread locally and we discuss difficulties in its detection without invasive sampling. In addition to the presence of S. haematobium, S. mattheei was noted alongside key concurrent sexually transmitted infections. From our findings, we point out that improved prevention and management of FGS is required, foremost, better availability and regular accessibility to praziquantel treatment is needed. Furthermore, targeted health education, raised community awareness and dovetailing synergistic public health activities within Sexual and Reproductive Health services and local HIV/AIDS programmes could develop an appropriate holistic health intervention package.
Despite increasing awareness and understanding of children’s victimisation through experiences of domestic violence (EDV), little attention has been given to the associated health outcomes.
Aim
Examine associations between four different forms of childhood EDV (physical violence, threats of harm, property damage and intimidation or control) and four mental disorders and six health risk behaviours.
Method
Data were drawn from the Australian Child Maltreatment Study. Associations were examined using survey-weighted logistic regression models. Estimates were calculated adjusting for each other form of EDV, as well as other types of child maltreatment and socio-economic factors. Each model was stratified for men and women.
Results
All mental disorders and health risk behaviours were more common among those with any childhood EDV compared to those without. Intimidation or control and damage to property or pets independently predicted most mental disorders and health risk behaviours. The strongest association was found between intimidation or control and post-traumatic stress disorder (adjusted odds ratio (aOR) 2.30, 95% CI 1.77–2.98) and generalised anxiety disorder (aOR 1.65, 95% CI 1.36–1.99), and damage to property or pets and severe alcohol use disorder (aOR 1.76, 95% CI 1.36–2.27).
Conclusions
Childhood EDV characterised by intimidation or control and property damage or harm to pets significantly increases the risk of mental disorders and health risk behaviours in adulthood. Urgent investment is needed in child-centred and trauma- and family-violence-informed interventions that support children’s recovery and stronger legal protections to prevent children from being weaponised in post-separation coercive control.
Punctuated equilibria argue for intervals of long-term net stasis and comparatively abrupt change in the morphology of individual species lineages resulting from the process of allopatric speciation as recorded in the stratigraphic and fossil record. The concept of coordinated stasis extends punctuated equilibria to posit that not only individual species, but groups of coexisting lineages within a basin, display concurrent morphological and ecological stability over the same extended intervals of geologic time (105 to 106 yr). These blocks of stability termed ecological–evolutionary subunits (EESUs) are separated by shorter-lived (on the order of 103 to 104 yr) episodes of change characterized by varying combinations of speciation, extinction, immigration, and emigration. The result is a pattern of evolutionary and ecological stasis and change that is coincident and highly punctuational.
Here, we assess the connections among environment, evolution, and ecology by documenting patterns of stability, geographic extent, and synchronous turnover during medium-scale bioevents in the Middle Devonian of the eastern United States, and we briefly compare these with patterns of EESUs across the Late Ordovician mass extinction (LOME) based on ongoing work. We quantify the geographic extent and stability of faunas originally documented in the Appalachian Basin and identify their likely places of origin and refugia during turnovers. Faunas are geographically widespread during times of stability and border comparably stable faunas in adjacent provinces. During geologically brief intervals, assemblages display near-synchronous shifts involving local extirpation/extinction and coordinated migration of biogeographic boundaries over very long distances. Allopatric speciation in small, locally isolated populations along the edges of basins during brief windows of dramatically altered environmental conditions is more consistent with the geological record, emphasizes the role of environment and biogeography in driving evolutionary change, and confirms the prevalence of punctuated equilibria.
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
Landscape evolution in karst terrains affects both subterranean and surface settings. For better understanding of controlling processes and connections between the two, multiple geochronometers were used to date sediments and speleothems in upper-level passages of Fitton Cave adjacent to the Buffalo River, northern Arkansas, within the southern Ozark Plateau. Burial cosmogenic-nuclide dating of coarse sediments indicates that gravel pulses washed into upper passages at 2.2 Ma and 1.25 Ma. These represent the oldest epigenetic cave deposits documented in this region. Associated sands and clay-rich sediments mostly have reversed magnetic polarity and thermally transferred optically stimulated luminescence dates of 1.2 to 1.0 Ma. Abandonment of these upper passages began before 0.72 Ma, when coarse sediment was deposited in a passage incised below older sediment. Maximum U-series dates of 0.7–0.4 Ma for flowstones capping clastic deposits mark the stabilization of older sediments and a change to vadose conditions that allowed post–0.4 Ma stalagmite growth. Resulting valley incision rates since 0.85 Ma are estimated at 27 m/Ma. Coarse cave-sediment pulses correlate to Laurentide glacial tills about 300 km to the north, suggesting climate influence on periglacial sediment production. Dated cave sediments also may correlate with undated older strath terraces preserved at similar heights above the Buffalo River.
Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Next-generation X-ray satellite telescopes such as XRISM, NewAthena and Lynx will enable observations of exotic astrophysical sources at unprecedented spectral and spatial resolution. Proper interpretation of these data demands that the accuracy of the models is at least within the uncertainty of the observations. One set of quantities that might not currently meet this requirement is transition energies of various astrophysically relevant ions. Current databases are populated with many untested theoretical calculations. Accurate laboratory benchmarks are required to better understand the coming data. We obtained laboratory spectra of X-ray lines from a silicon plasma at an average spectral resolving power of $\sim$7500 with a spherically bent crystal spectrometer on the Z facility at Sandia National Laboratories. Many of the lines in the data are measured here for the first time. We report measurements of 53 transitions originating from the K-shells of He-like to B-like silicon in the energy range between $\sim$1795 and 1880 eV (6.6–6.9 Å). The lines were identified by qualitative comparison against a full synthetic spectrum calculated with ATOMIC. The average fractional uncertainty (uncertainty/energy) for all reported lines is ${\sim}5.4 \times 10^{-5}$. We compare the measured quantities against transition energies calculated with RATS and FAC as well as those reported in the NIST ASD and XSTAR’s uaDB. Average absolute differences relative to experimentally measured values are 0.20, 0.32, 0.17 and 0.38 eV, respectively. All calculations/databases show good agreement with the experimental values; NIST ASD shows the closest match overall.
Parent depression is a well-established prospective risk factor for adverse offspring mental health. Multiple lines of evidence suggest that improvements in parent depression predicts improved offspring mental health. However, no systematic review has examined the impact on offspring of psychological treatment of purely parent depression after the postnatal period.
Aims:
To systematically review the literature of randomised controlled trials examining the impact on offspring mental health outcomes of psychological interventions for parental depression after the postnatal period.
Method:
We pre-registered our systematic review on PROSPERO (CRD42023408953), and searched the METAPSY database in April 2023 and October 2024, for randomised controlled trials of psychological interventions for adults with depression, which also included a child mental health or wellbeing outcome. We double screened 938 studies for inclusion using the ‘Paper in a Day’ approach. All included studies would be rated using the Cochrane Risk of Bias tool.
Results:
We found no studies that met our inclusion criteria.
Conclusions:
Robust research into psychological therapy for depression in adults outside the postnatal period has failed to consider the potential benefits for the children of those adults. This is a missed clinical opportunity to evaluate the potential preventive benefits for those children at risk of adverse psychological outcomes, and a missed scientific opportunity to test mechanisms of intergenerational transmission of risk for psychopathology. Seizing the clinical and scientific opportunities would require adult-focused mental health researchers to make inexpensive additions of child mental health outcomes measures to their evaluation projects.
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.
Most cognitive studies of bipolar disorder (BD) have examined case–control differences on cognitive tests using measures of central tendency, which do not consider intraindividual variability (IIV); a distinct cognitive construct that reliably indexes meaningful cognitive differences between individuals. In this study, we sought to characterize IIV in BD by examining whether it differs from healthy controls (HCs) and is associated with other cognitive measures, clinical variables, and white matter microstructure.
Methods
Two hundred and seventeen adults, including 100 BD outpatients and 117 HCs, completed processing speed, sustained attention, working memory, and executive function tasks. A subsample of 55 BD participants underwent diffusion tensor imaging. IIV was operationalized as the individual standard deviation in reaction time on the Continuous Performance Test-Identical Pairs version.
Results
BD participants had significantly increased IIV compared to age-matched controls. Increased IIV was associated with poorer mean performance scores on processing speed, sustained attention, working memory, and executive function tasks, as well as two whole-brain white matter indices: fractional anisotropy and radial diffusivity.
Conclusions
IIV is increased in BD and appears to correlate with other cognitive variables, as well as white matter measures that index reduced structural integrity and demyelination. Thus, IIV may represent a neurobiologically informative cognitive measure for BD research that is worthy of further investigation.
This study examined whether supplementation with collagen peptides (CP) affects appetite and post-exercise energy intake in healthy active females. In this randomised, double-blind cross-over study, fifteen healthy females (23 (sd 3) years) consumed 15 g/d of CP or a taste matched non-energy control (CON) for 7 d. On day 7, participants cycled for 45 min at ∼55 % Wmax, before consuming the final supplement. Sixty-min post supplementation an ad libitum meal was provided, and energy intake recorded. Subjective appetite sensations were measured daily for 6 d (pre- and 30 min post-supplement) and pre (0 min) to 280 min post-exercise on day 7. Blood glucose and hormone concentrations (total ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY), cholecystokinin (CCK), dipeptidyl peptidase-4 (sDPP-4), leptin, and insulin) were measured fasted at baseline (day 0), then pre-breakfast (0 min), post-exercise (100 min), post-supplement (115, 130, 145, 160 min) and post-meal (220, 280 min) on day 7. Ad libitum energy intake was ∼10 % (∼41 kcal) lower in the CP trial (P = 0·037). There was no difference in gastrointestinal symptoms or subjective appetite sensations throughout the trial (P ≥ 0·412). Total plasma GLP-1 (AUC, CON: 6369 (sd 2330); CP: 9064 (sd 3021) pmol/l; P < 0·001) and insulin (+80 % at peak) were higher after CP (P < 0·001). Plasma ghrelin and leptin were lower in CP (condition effect; P ≤ 0·032). PYY, CCK and glucose were not different between CP and placebo (P ≥ 0·100). CP supplementation following exercise increased GLP-1 and insulin concentrations and reduced ad libitum energy intake at a subsequent meal in physically active females.
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.
Following the recent report of strongyloidiasis caused by Strongyloides fuelleborni within a semi-captive colony of baboons in a UK safari park, we investigated the genetic relationships of this isolate with other Strongyloides isolates across the world. Whole-genome sequencing data were generated with later phylogenetic analysis of mitochondrial (mt) cytochrome oxidase subunit 1 (cox1) and nuclear ribosomal 18S sequences against 300 published Strongyloides reference genotypes. The putative African origin of the UK S. fuelleborni was confirmed and full-length mt genome sequences were assembled to facilitate a more detailed phylogenetic analysis of 14 mt coding regions against all available Strongyloides species. Our analyses demonstrated that the UK isolate represented a novel African lineage not previously described. Additional complete mt genomes were assembled for several individual UK safari park worms to reveal a slightly altered mt genome gene arrangement, allowing clear separation from Asian S. fuelleborni. Furthermore, these UK worms possessed expanded intergenic regions of unknown function that increase their mt genome size to approximately 24 kilobases (kb) as compared with some 16 kb for Asian S. fuelleborni; this may have arisen from unique populational founder and genetic drift effects set within the peculiar mixed species baboon and drill ancestry of this semi-captive primate colony. A maximum likelihood phylogeny constructed from 14 mt coding regions also supported an evolutionary distinction between Asian and African S. fuelleborni.
Objectives/Goals: We describe the prevalence of individuals with household exposure to SARS-CoV-2, who subsequently report symptoms consistent with COVID-19, while having PCR results persistently negative for SARS-CoV-2 (S[+]/P[-]). We assess whether paired serology can assist in identifying the true infection status of such individuals. Methods/Study Population: In a multicenter household transmission study, index patients with SARS-CoV-2 were identified and enrolled together with their household contacts within 1 week of index’s illness onset. For 10 consecutive days, enrolled individuals provided daily symptom diaries and nasal specimens for polymerase chain reaction (PCR). Contacts were categorized into 4 groups based on presence of symptoms (S[+/-]) and PCR positivity (P[+/-]). Acute and convalescent blood specimens from these individuals (30 days apart) were subjected to quantitative serologic analysis for SARS-CoV-2 anti-nucleocapsid, spike, and receptor-binding domain antibodies. The antibody change in S[+]/P[-] individuals was assessed by thresholds derived from receiver operating characteristic (ROC) analysis of S[+]/P[+] (infected) versusS[-]/P[-] (uninfected). Results/Anticipated Results: Among 1,433 contacts, 67% had ≥1 SARS-CoV-2 PCR[+] result, while 33% remained PCR[-]. Among the latter, 55% (n = 263) reported symptoms for at least 1 day, most commonly congestion (63%), fatigue (63%), headache (62%), cough (59%), and sore throat (50%). A history of both previous infection and vaccination was present in 37% of S[+]/P[-] individuals, 38% of S[-]/P[-], and 21% of S[+]/P[+] (P<0.05). Vaccination alone was present in 37%, 41%, and 52%, respectively. ROC analyses of paired serologic testing of S[+]/P[+] (n = 354) vs. S[-]/P[-] (n = 103) individuals found anti-nucleocapsid data had the highest area under the curve (0.87). Based on the 30-day antibody change, 6.9% of S[+]/P[-] individuals demonstrated an increased convalescent antibody signal, although a similar seroresponse in 7.8% of the S[-]/P[-] group was observed. Discussion/Significance of Impact: Reporting respiratory symptoms was common among household contacts with persistent PCR[-] results. Paired serology analyses found similar seroresponses between S[+]/P[-] and S[-]/P[-] individuals. The symptomatic-but-PCR-negative phenomenon, while frequent, is unlikely attributable to true SARS-CoV-2 infections that go missed by PCR.