Ubiquitous atmospheric production of organic acids mediated by cloud droplets.

Atmospheric acidity is increasingly determined by carbon dioxide and organic acids1-3. Among the latter, formic acid facilitates the nucleation of cloud droplets4 and contributes to the acidity of clouds and rainwater1,5. At present, chemistry-climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood2,6-9. Here we present atmospheric chamber experiments that show that formaldehyde is efficiently converted to gaseous formic acid via a multiphase pathway that involves its hydrated form, methanediol. In warm cloud droplets, methanediol undergoes fast outgassing but slow dehydration. Using a chemistry-climate model, we estimate that the gas-phase oxidation of methanediol produces up to four times more formic acid than all other known chemical sources combined. Our findings reconcile model predictions and measurements of formic acid abundance. The additional formic acid burden increases atmospheric acidity by reducing the pH of clouds and rainwater by up to 0.3. The diol mechanism presented here probably applies to other aldehydes and may help to explain the high atmospheric levels of other organic acids that affect aerosol growth and cloud evolution.

Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography.

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)'s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).

Sun-related knowledge and practices in Irish construction and agricultural workers.

BACKGROUND: Agricultural and construction workers spend much of their work time outdoors and have higher risks of developing skin cancer when compared to indoor workers. However, there is limited research on ultraviolet radiation (UVR) exposure knowledge, sun safety practices and constraints within these occupational groups in Ireland. AIMS: This study aimed to examine self-reported time spent outdoors in a sample of Irish agricultural and construction workers; to describe and compare UVR exposure knowledge, safety practices and perceived constraints in both occupational groups, and to assess the association of demographic, personal and occupational factors with sun-related knowledge, practices and perceived constraints. METHODS: Agricultural workers (n = 154) and construction workers (n = 467) completed a questionnaire, which measured solar UVR exposure knowledge, safety practices, and perceived constraints to sun personal protective equipment and sunscreen use in addition to demographic, personal, and workplace characteristics. Mann-Whitney and Kruskal-Wallis tests were used to examine differences in knowledge, practices and perceived constraints by these characteristics. RESULTS: Both groups spend a significant proportion of their working week outdoors (25 hours per week on average). Although participation in sun safety training was high for both groups, UVR exposure knowledge and sunscreen use were low, and annual rates of reported sunburn were high. Knowledge, practices and perceived constraints also differed significantly according to demographic, personal, occupational and workplace characteristics. CONCLUSIONS: In addition to training by employers and advisory groups, interventions are required to address perceived barriers that impede the uptake and usage of control measures that can lower risk.

Perceptions of climate change and associated health impacts among communities in Johor River Basin, Malaysia.

INTRODUCTION: As climate change is threatening every region of the world, extreme weather events resultant of global warming is occurring at increasing rate and scale in Malaysia. Weather-related disasters such as flood and haze pose critical challenges to the infrastructure and raise public health concerns in the country, especially when main economic sectors rely heavily on climate variability. Public perception on environmental issues is crucial for development of pro-environmental policies. Among studies conducted to understand public awareness regarding global warming, reports of perception on the health impacts were very limited. Taking this limitation into account, this study was designed to examine the perception on the health impacts of climate change among the diverse communities living in the Johor River Basin. MATERIALS AND METHODS: The cross-sectional study was conducted through cloud-data-based digital questionnaires completed by randomly selected residents in the Johor River Basin (n=647). Data was analysed with descriptive statistics using SPSS 27 (IBM®) Software. Comparisons between indigenous and non-indigenous communities were performed using Chi square analysis. RESULTS: Respondents in this study consisted of indigenous people (n=79) and non-indigenous people (n=568). Indigenous respondents generally perceived more frequent occurrence of extreme weather events in the next 20 years, even for the phenomena unfamiliar in Malaysian settings. All respondents showed similar concerns for health impacts of global warming, although the non-indigenous respondents perceived the risk further into the future (25 years) compared to the indigenous respondents who perceived current or imminent (<10 years) risks. Intense concerns for self, children, family members and community were shown by nearly all indigenous respondents (97-99%), while the non-indigenous people in this study expressed stronger concerns at country level and for future generations. During the last haze episode, most indigenous respondents (85%) did not notice any change in air quality nor discomfort among family members, in contrast 70% of the nonindigenous respondents claimed to have suffered from breathing problems themselves as well as others in the family. All respondents were concerned about air quality in their surroundings, indigenous people were concerned for the near future (<10 years), and non-indigenous people were concerned for the next 25 years. CONCLUSION: In this study, respondents were generally concerned about the health impacts of unimpeded global warming. There was significant difference in perceptions between indigenous and non-indigenous respondents. The findings were useful, complemented with further studies, to improve understanding of public awareness and to help develop relevant education programmes accessible for wider audience.

Investigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepoints.

BACKGROUND: Distinct sets of microbes contribute to colorectal cancer (CRC) initiation and progression. Some occur due to the evolving intestinal environment but may not contribute to disease. In contrast, others may play an important role at particular times during the tumorigenic process. Here, we describe changes in the microbiota and host over the course of azoxymethane (AOM)-induced tumorigenesis. METHODS: Mice were administered AOM or PBS and were euthanised 8, 12, 24 and 48 weeks later. Samples were analysed using 16S rRNA gene sequencing, UPLC-MS and qRT-PCR. RESULTS: The microbiota and bile acid profile showed distinct changes at each timepoint. The inflammatory response became apparent at weeks 12 and 24. Moreover, significant correlations between individual taxa, cytokines and bile acids were detected. One co-abundance group (CAG) differed significantly between PBS- and AOM-treated mice at week 24. Correlation analysis also revealed significant associations between CAGs, bile acids and the bile acid transporter, ASBT. Aberrant crypt foci and adenomas were first detectable at weeks 24 and 48, respectively. CONCLUSION: The observed changes precede host hyperplastic transformation and may represent early therapeutic targets for the prevention or management of CRC at specific timepoints in the tumorigenic process.

Measurement of Magnetic Cavitation Driven by Heat Flow in a Plasma.

We describe the direct measurement of the expulsion of a magnetic field from a plasma driven by heat flow. Using a laser to heat a column of gas within an applied magnetic field, we isolate Nernst advection and show how it changes the field over a nanosecond timescale. Reconstruction of the magnetic field map from proton radiographs demonstrates that the field is advected by heat flow in advance of the plasma expansion with a velocity v_{N}=(6±2)×10^{5} m/s. Kinetic and extended magnetohydrodynamic simulations agree well in this regime due to the buildup of a magnetic transport barrier.

Validity of the DSM-5 craving criterion for alcohol, tobacco, cannabis, cocaine, heroin, and non-prescription use of prescription painkillers (opioids).

BACKGROUND: Although the DSM-5 was adopted in 2013, the validity of the new substance use disorder (SUD) diagnosis and craving criterion has not been investigated systematically across substances. METHODS: Adults (N = 588) who engaged in binge drinking or illicit drug use and endorsed at least one DSM-5 SUD criterion were included. DSM-5 SUD criteria were assessed for alcohol, tobacco, cannabis, cocaine, heroin, and opioids. Craving was considered positive if "wanted to use so badly that could not think of anything else" (severe craving) or "felt a very strong desire or urge to use" (moderate craving) was endorsed. Baseline information on substance-related variables and psychopathology was collected, and electronic daily assessment queried substance use for the following 90 days. For each substance, logistic regression estimated the association between craving and validators, i.e. variables expected to be related to craving/SUD, and whether association with the validators differed for DSM-5 SUD diagnosed with craving as a criterion v. without. RESULTS: Across substances, craving was associated with most baseline validators (p values<0.05); neither moderate nor severe craving consistently showed greater associations. Baseline craving predicted subsequent use [odds ratios (OR): 4.2 (alcohol) - 234.3 (heroin); p's ⩽ 0.0001], with stronger associations for moderate than severe craving (p's < 0.05). Baseline DSM-5 SUD showed stronger associations with subsequent use when diagnosed with craving than without (p's < 0.05). CONCLUSION: The DSM-5 craving criterion as operationalized in this study is valid. Including craving improves the validity of DSM-5 SUD diagnoses, and clinical relevance, since craving may cause impaired control over use and development and maintenance of SUD.

Effect of Strongly Magnetized Electrons and Ions on Heat Flow and Symmetry of Inertial Fusion Implosions.

This Letter presents the first observation on how a strong, 500 kG, externally applied B field increases the mode-two asymmetry in shock-heated inertial fusion implosions. Using a direct-drive implosion with polar illumination and imposed field, we observed that magnetization produces a significant increase in the implosion oblateness (a 2.5× larger P2 amplitude in x-ray self-emission images) compared with reference experiments with identical drive but with no field applied. The implosions produce strongly magnetized electrons (ω_{e}τ_{e}≫1) and ions (ω_{i}τ_{i}>1) that, as shown using simulations, restrict the cross field heat flow necessary for lateral distribution of the laser and shock heating from the implosion pole to the waist, causing the enhanced mode-two shape.

Increased Ion Temperature and Neutron Yield Observed in Magnetized Indirectly Driven D_{2}-Filled Capsule Implosions on the National Ignition Facility.

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9 kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3 µs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment.

Personal dosimetry for positron emitters, and occupational exposures from clinical use of gallium-68.

The current status and issues regarding positron dosimetry in nuclear medicine are summarized. The suitability of the United Kingdom Health Security Agency extremity and eye beta-gamma personal thermoluminescence dosemeters are then considered. Monte Carlo modelling is performed to determine their responses and derive sets of calibration factors, along withHp(0.07) andHp(3) conversion coefficients, for carbon-11, nitrogen-13, oxygen-15, fluorine-18 and gallium-68 sources, which are commonly used in positron emission tomography (PET) computed tomography; data for these isotopes is assumed extrapolatable to other positron sources. It is found that the dosemeters are adequate for assessing exposures to PET radionuclides, even if their routine calibrations to caesium-137 were maintained. An idealized set of measurements representing gallium-68 exposure scenarios is then described, including reproducible mock-ups of individuals manipulating vials and syringes. Finally, a short case-study is presented that explores occupational doses during routine clinical use of gallium-68. The extremity dosemeter results demonstrated significant variations dependent upon the exposure conditions, with some seen to be comparatively large; whole-body and eye dose rates per activity were found to be lower. The importance of routine dose monitoring of workers is emphasized, with the need for a longer-termed follow-up study demonstrated.

Feasibility study of computational occupational dosimetry: evaluating a proof-of-concept in an endovascular and interventional cardiology setting.

Individual monitoring of radiation workers is essential to ensure compliance with legal dose limits and to ensure that doses are As Low As Reasonably Achievable. However, large uncertainties still exist in personal dosimetry and there are issues with compliance and incorrect wearing of dosimeters. The objective of the PODIUM (Personal Online Dosimetry Using Computational Methods) project was to improve personal dosimetry by an innovative approach: the development of an online dosimetry application based on computer simulations without the use of physical dosimeters. Occupational doses were calculated based on the use of camera tracking devices, flexible individualised phantoms and data from the radiation source. When combined with fast Monte Carlo simulation codes, the aim was to perform personal dosimetry in real-time. A key component of the PODIUM project was to assess and validate the methodology in interventional radiology workplaces where improvements in dosimetry are needed. This paper describes the feasibility of implementing the PODIUM approach in a clinical setting. Validation was carried out using dosimeters worn by Vascular Surgeons and Interventional Cardiologists during patient procedures at a hospital in Ireland. Our preliminary results from this feasibility study show acceptable differences of the order of 40% between calculated and measured staff doses, in terms of the personal dose equivalent quantity Hp(10), however there is a greater deviation for more complex cases and improvements are needed. The challenges of using the system in busy interventional rooms have informed the future needs and applicability of PODIUM. The availability of an online personal dosimetry application has the potential to overcome problems that arise from the use of current dosimeters. In addition, it should increase awareness of radiation protection among staff. Some limitations remain and a second phase of development would be required to bring the PODIUM method into operation in a hospital setting. However, an early prototype system has been tested in a clinical setting and the results from this two-year proof-of-concept PODIUM project are very promising for future development.

Abundant molecular oxygen in the coma of comet 67P/Churyumov-Gerasimenko.

The composition of the neutral gas comas of most comets is dominated by H2O, CO and CO2, typically comprising as much as 95 per cent of the total gas density. In addition, cometary comas have been found to contain a rich array of other molecules, including sulfuric compounds and complex hydrocarbons. Molecular oxygen (O2), however, despite its detection on other icy bodies such as the moons of Jupiter and Saturn, has remained undetected in cometary comas. Here we report in situ measurement of O2 in the coma of comet 67P/Churyumov-Gerasimenko, with local abundances ranging from one per cent to ten per cent relative to H2O and with a mean value of 3.80 ± 0.85 per cent. Our observations indicate that the O2/H2O ratio is isotropic in the coma and does not change systematically with heliocentric distance. This suggests that primordial O2 was incorporated into the nucleus during the comet's formation, which is unexpected given the low upper limits from remote sensing observations. Current Solar System formation models do not predict conditions that would allow this to occur.

Magnetic Signatures of Radiation-Driven Double Ablation Fronts.

In experiments performed with the OMEGA EP laser system, magnetic field generation in double ablation fronts was observed. Proton radiography measured the strength, spatial profile, and temporal dynamics of self-generated magnetic fields as the target material was varied between plastic, aluminum, copper, and gold. Two distinct regions of magnetic field are generated in mid-Z targets-one produced by gradients from electron thermal transport and the second from radiation-driven gradients. Extended magnetohydrodynamic simulations including radiation transport reproduced key aspects of the experiment, including field generation and double ablation front formation.

Long-term outcomes of real world 'watch and wait' data for rectal cancer after neoadjuvant chemoradiotherapy.

AIM: A 'watch and wait' (W&W) strategy after neoadjuvant long-course chemoradiotherapy (NACRT) remains controversial. Whilst encouraging short-term data exist, the strategy will be judged on long-term data. We present long-term, real-world UK data from a single National Health Service trust. METHODS: An analysis was performed of a prospectively maintained W&W database over 9 years between 2010 and 2018. Outcome measures include incidence and time to regrowth and overall and disease-free survival. RESULTS: We diagnosed 563 rectal cancers in 9 years. In all, 283 patients underwent rectal resection (50.3%). NACRT was used in 155 patients for margin-threatened tumours on staging MRI. Forty-nine patients (31.6%) experienced either a 'near complete' or a complete clinical response (cCR) at their 10 weeks post-NACRT assessment (MRI and endoscopy). The median age was 69 years (range 44-83), and the male to female ratio was 32:17. The median follow-up was 38 months (range 12-96). The median tumour distance from the anal verge was 7 cm (1-15 cm). Twenty-two patients had a cCR on initial assessment and 27 patients had a 'near' cCR. Of those 27 who experienced a 'near' cCR, 17 (63%) progressed to cCR on repeat assessment and 10 (37%) did not. Of these 10 patients, seven underwent standard surgical resection and three were unfit for surgery. R0 for the seven with delayed resection was 100%. Of 39 patients (22 cCR and 17 'near' cCR who progressed to cCR) (25.2% of those receiving NACRT), six patients experienced local regrowth (15.4%). The median time to local regrowth was 29 months (15-60 months). One of these six patients underwent salvage abdominoperineal resection, one was advised to have contact radiotherapy and four opted against surgery and also had contact radiotherapy. The overall survival was 100% at 2 years and 90% at 5 years. Disease-free survival was 90.47% at 2 years and 74.8% at 5 years. CONCLUSION: A W&W treatment strategy was employed safely in this patient cohort with acceptable rates of local regrowth and survival.

Recent Northern Hemisphere stratospheric HCl increase due to atmospheric circulation changes.

The abundance of chlorine in the Earth's atmosphere increased considerably during the 1970s to 1990s, following large emissions of anthropogenic long-lived chlorine-containing source gases, notably the chlorofluorocarbons. The chemical inertness of chlorofluorocarbons allows their transport and mixing throughout the troposphere on a global scale, before they reach the stratosphere where they release chlorine atoms that cause ozone depletion. The large ozone loss over Antarctica was the key observation that stimulated the definition and signing in 1987 of the Montreal Protocol, an international treaty establishing a schedule to reduce the production of the major chlorine- and bromine-containing halocarbons. Owing to its implementation, the near-surface total chlorine concentration showed a maximum in 1993, followed by a decrease of half a per cent to one per cent per year, in line with expectations. Remote-sensing data have revealed a peak in stratospheric chlorine after 1996, then a decrease of close to one per cent per year, in agreement with the surface observations of the chlorine source gases and model calculations. Here we present ground-based and satellite data that show a recent and significant increase, at the 2σ level, in hydrogen chloride (HCl), the main stratospheric chlorine reservoir, starting around 2007 in the lower stratosphere of the Northern Hemisphere, in contrast with the ongoing monotonic decrease of near-surface source gases. Using model simulations, we attribute this trend anomaly to a slowdown in the Northern Hemisphere atmospheric circulation, occurring over several consecutive years, transporting more aged air to the lower stratosphere, and characterized by a larger relative conversion of source gases to HCl. This short-term dynamical variability will also affect other stratospheric tracers and needs to be accounted for when studying the evolution of the stratospheric ozone layer.

Levator avulsion and vaginal parity: do subsequent vaginal births matter?

INTRODUCTION AND HYPOTHESIS: Tears of the levator ani muscle are common after vaginal birth and associated with pelvic organ prolapse (POP). Although such trauma is usually attributed to the first vaginal birth, epidemiological evidence suggests an additional effect of subsequent vaginal deliveries. Our hypothesis was: "The prevalence of avulsion increases with the number of vaginal births". METHODS: We conducted a retrospective cohort study in patients who presented to a tertiary urogynaecology clinic. Assessment included a physician-directed interview, POP-Q and 4D translabial ultrasound (TLUS), supine, after voiding, at rest, on maximum pelvic floor muscle contraction (PFMC) and Valsalva. Offline analysis of levator integrity was undertaken by tomographic imaging (TUI) at a later date, blinded against all other data. RESULTS: A total of 1,124 patients had been seen between 1 January 2014 and 30 June 2016, on average 33 (0.32-69.7) years after their first birth. Mean age was 56 (19-90) years. 1,012 (90%) were vaginally parous with a median vaginal parity of 2 (1-8). On TUI, avulsion was diagnosed in 257 (23%) women, all of whom were vaginally parous. On univariate analysis, there was no significant difference in the prevalence of avulsion on comparing vaginally primiparous and multiparous women (P = 0.6), nor was there any difference between vaginal parity groups (one, two, three, and ≥4 births; p = 0.7). This remained true after controlling for potential confounding factors using multivariate regression (p = 0.6). CONCLUSIONS: There was no significant difference in the prevalence of avulsion between vaginally primiparous and multiparous women. Vaginal deliveries after a first vaginal birth are unlikely to cause avulsion.

Sacrococcygeal dimensions and curvature are associated with resection quality in rectal cancer excision.

BACKGROUND: Technical factors affect oncologic outcomes in rectal cancer surgery. The anatomy of the bony pelvis can affect technical aspects of surgery, but is seldom considered preoperatively. We performed a morphometric analysis of the bony pelvis in patients having rectal cancer resection to assess its effect on surgical specimen quality. METHODS: We performed a retrospective analysis of a prospectively maintained database of patients who had resection for rectal cancer from January 2014 to December 2017. Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) images were accessed and measurements of sacrococcygeal distance, sacrococcygeal recess depth/area, sacrococcygeal angulation, anteroposterior pelvic inlet/outlet, pubic height and interspinous distance were made. Outcome measures included anatomical variation, operating time and mesorectal specimen grade. In patients having extra-levator abdominoperineal excision (eLAPE) with coccygectomy, the completeness of coccygeal resection was assessed by postoperative CT scan. Data were analysed using binomial and multinomial logistic regression and linear regression. RESULTS: One hundred and twenty-two consecutive rectal cancer resections were performed (39 open, 42 laparoscopic, 12 laparoscopic-converted and 29 robotic). The median age was 72 years (range: 29-88 years). The male:female ratio was 83:39. Eighty-one patients had anterior resection, 8 had low Hartmann's resection and 32 had APE. Of those who had APE, 21 had eLAPE (all with coccygectomy). Females had a larger pelvic inlet (female: 124.9 mm, male: 114.9 mm), interspinous diameter(female:112.8 mm, male:97.6 mm), sacrococcygeal depth (female:42.6 mm, 39.35 mm) and sacrococcygeal area recess than males (female: 3697 mm2, male: 3481.5 mm2). Males had a greater pubic height (female: 51.8 mm, male: 54.05 mm) and greater sacrococcygeal distance (female: 116.7 mm, male: 123.65 mm) than females. In patients having anterior resection, tumour distance from the anal verge (p = 0.004), sacrococcygeal distance (p = 0.006) and sacrococcygeal curvature (p = 0.002) were associated with specimen quality. In patients who had eLAPE, median preoperative coccygeal length was 41 mm (IQR: 35.1-45.5). The median length of coccygeal resection was 9 mm (IQR: 1-17.45 mm). The median length of coccyx remaining postoperatively was 33 mm (IQR: 21.35-39 mm). CONCLUSIONS: Sacrococcygeal curvature and distance as well as tumour distance from the anal margin were associated with specimen quality in anterior resection. Coccygectomy was not performed as completely as surgeons thought. Surgeons should include sacrococcygeal bony anatomy in rectal cancer surgical planning to potentially improve outcomes in both anterior resection and eLAPE approaches.

Local Entanglement Entropy and Mutual Information across the Mott Transition in the Two-Dimensional Hubbard Model.

Entanglement and information are powerful lenses to probe phases transitions in many-body systems. Motivated by recent cold atom experiments, which are now able to measure the corresponding information-theoretic quantities, we study the Mott transition in the half-filled two-dimensional Hubbard model using cellular dynamical mean-field theory, and focus on two key measures of quantum correlations: entanglement entropy and a measure of total mutual information. We show that they detect the first-order nature of the transition, the universality class of the end point, and the crossover emanating from the end point.

Early Electrophysiological Disintegration of Hippocampal Neural Networks in a Novel Locus Coeruleus Tau-Seeding Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by loss of synapses and disrupted functional connectivity (FC) across different brain regions. Early in AD progression, tau pathology is found in the locus coeruleus (LC) prior to amyloid-induced exacerbation of clinical symptoms. Here, a tau-seeding model in which preformed synthetic tau fibrils (K18) were unilaterally injected into the LC of P301L mice, equipped with multichannel electrodes for recording EEG in frontal cortical and CA1-CA3 hippocampal areas, was used to longitudinally quantify over 20 weeks of functional network dynamics in (1) power spectra; (2) FC using intra- and intersite phase-amplitude theta-gamma coupling (PAC); (3) coherence, partial coherence, and global coherent network efficiency (Eglob) estimates; and (4) the directionality of functional connectivity using extended partial direct coherence (PDC). A sustained leftward shift in the theta peak frequency was found early in the power spectra of hippocampal CA1 networks ipsilateral to the injection site. Strikingly, hippocampal CA1 coherence and Eglob measures were impaired in K18-treated animals. Estimation of instantaneous EEG amplitudes revealed deficiency in the propagation directionality of gamma oscillations in the CA1 circuit. Impaired PAC strength evidenced by decreased modulation of the theta frequency phase on gamma frequency amplitude further confirms impairments of the neural CA1 network. The present results demonstrate early dysfunctional hippocampal networks, despite no spreading tau pathology to the hippocampus and frontal cortex. The ability of the K18 seed in the brainstem LC to elicit such robust functional alterations in distant hippocampal structures in the absence of pathology challenges the classic view that tau pathology spread to an area is necessary to elicit functional impairments in that area.

Changes in temperament over time in young children with autism spectrum disorder and other developmental delays: a follow-up comparison study.

BACKGROUND: Although in the last decade some research has emerged on temperament in autism spectrum disorder (ASD), this research has primarily focused on the differences between children with ASD and their typically developing peers rather than the stability or change in temperament in this population. Thus, the goal of this study was to examine temperament over time in children with ASD, developmental delays (DD) and typical development (TD). Temperament differences were also compared among the three groups. METHODS: To accomplish this, parents rated children's temperament at Time 1 (T1) and Time 2 (T2) using the Carey Temperament Scales (CTS). RESULTS: Results from the study showed that at T1, parents of children with ASD rated their children as more withdrawn (i.e. approach), and emotionally negative (i.e. mood), and less distractible and adaptable than parents of children with TD and DD. Also, children with ASD were rated as more intense and children with DD as less distractible than their TD peers. Similarly, at T2, children with ASD were rated more withdrawn, and emotionally negative, and less persistent, rhythmic, adaptable and distractible than children with TD and DD. Also, children with ASD were rated as more active than their DD peers. Regarding stability, parent ratings of temperament appeared stable over time in the TD group, but ratings varied substantially in the ASD or DD groups. That is, for the ASD group, activity and approach at T1 were significantly associated with their corresponding dimensions at T2. However, for the TD group, rhythmicity, approach, intensity and mood at T1 were significantly associated with those dimensions at T2. No associations were found in the DD group. Regarding change, parents reported change in rhythmicity, persistence and threshold between T1 and T2 in the ASD group. Similarly, parents reported change in rhythmicity, approach and threshold between T1 and T2 in the DD group. Lastly, parents of TD children reported change in adaptability, persistence and distractibility between T1 and T2. CONCLUSIONS: These findings are novel in that children with ASD appear to have less stable temperament profile and different change patterns than children with TD or DD. Similar to previous research, children with ASD were described by their parents as experiencing more temperamental difficulties.