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Abstract INTRODUCTION Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated. METHODS We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD. RESULTS We examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (p = 0.09). Argyrophilic grain disease was associated with atypical presentation (p = 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (p = 0.022). Atypical cases had a steeper Mini‐Mental Status Examination (MMSE) decline over time (p = 0.033). DISCUSSION Comorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort. Highlights Autopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation? Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (p = 0.09). Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (p = 0.008). Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (p = 0.022). Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (p = 0.033).

Abstract Introduction Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are the most common four‐repeat tauopathies (4RT), and both frequently occur with varying degree of Alzheimer's disease (AD) copathology. Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum—AD showing reduced wakefulness and excessive sleepiness whereas 4RT showing decreased homeostatic sleep. The neural mechanisms underlying these distinct phenotypes in the comorbid condition of 4RT and AD are unknown. The objective of the current study was to define the alpha oscillatory spectrum, which is prominent in the awake resting‐state in the human brain, in patients with primary 4RT, and how it is modified in comorbid AD‐pathology. Method In an autopsy‐confirmed case series of 4R‐tauopathy patients (n = 10), whose primary neuropathological diagnosis was either PSP (n = 7) or CBD (n = 3), using high spatiotemporal resolution magnetoencephalography (MEG), we quantified the spectral power density within alpha‐band (8–12 Hz) and examined how this pattern was modified in increasing AD‐copathology. For each patient, their regional alpha power was compared to an age‐matched normative control cohort (n = 35). Result Patients with 4RT showed increased alpha power but in the presence of AD‐copathology alpha power was reduced. Conclusions Alpha power increase in PSP‐tauopathy and reduction in the presence of AD‐tauopathy is consistent with the observation that neurons activating wakefulness‐promoting systems are preserved in PSP but degenerated in AD. These results highlight the selectively vulnerable impacts in 4RT versus AD‐tauopathy that may have translational significance on disease‐modifying therapies for specific proteinopathies.

Abstract To explore the effect of conduit roughness on volcanic jet dynamics and on the related seismo‐acoustic radiation we performed a series of shock‐tube experiments using pipes with variable inner surface fractal dimension D. Variable starting pressure produced subsonic to supersonic jets visualized using high‐speed shadowgraph and recorded with an array of accelerometers and microphones. At all starting pressures, increasing D increases the energy transfer from the gas to the conduit walls, decreasing the jet exit velocity (Mach number) and, for supersonic cases, the related shock‐cell spacing, and increasing the seismic to acoustic radiation amplitude ratio. The roughness‐induced changes in jet velocity and turbulence affect the dominant sources of the jet noise and modulates the spectral properties of the acoustic signals. From our study we show that conduit wall roughness is an important and yet largely neglected factor in the dynamics of explosive volcanic eruptions and their monitored geophysical signals.

Abstract Host‐associated bacterial microbiomes can facilitate host acclimation to seasonal environmental change and are hypothesized to help hosts cope with recent anthropogenic environmental perturbations (e.g., landscape modification). However, it is unclear how recurrent and recent forms of environmental change interact to shape variation in the microbiome. The majority of wildlife microbiome research occurs within a single seasonal context. Meanwhile, the few studies of seasonal variation in the microbiome often restrict focus to a single environmental context. By sampling urban and exurban eastern grey squirrel populations in the spring, summer, autumn, and winter, we explored whether seasonal rhythms in the grey squirrel gut microbiome differed across environments using a 16S amplicon sequencing approach. Differences in the microbiome between urban and exurban squirrels persisted across most of the year, which we hypothesize is linked to anthropogenic food consumption, but we also observed similarities in the urban and exurban grey squirrel microbiome during the autumn, which we attribute to engrained seed caching instincts in preparation for the winter. Host behaviour and diet selection may therefore be capable of maintaining similarities in microbiome structure between disparate environments. However, the depletion of an obligate host mucin glycan specialist (Akkermansia) during the winter in both urban and exurban squirrels was among the strongest differential abundance patterns we observed. In summary, urban grey squirrels showed different seasonal patterns in their microbiome than squirrels from exurban forests; however, in some instances, host behaviour and physiological responses might be capable of maintaining similar microbiome responses across seasons.

Abstract Objective The objective of this study is to estimate the prevalence of epilepsy with Tonic–Clonic (TC) seizures in rural areas of the Bolivian Gran Chaco and to evaluate the usefulness of telemedicine in this context. Methods The study was carried out in the Isozo Area, southern‐eastern Bolivia. Twenty‐five rural communities with a population of 8258 inhabitants were included in the survey. Trained community‐health workers administered a validated single screening question to the householders (stage I). A second face‐to‐face questionnaire was administered to each positive subject (stage II). At stage II subjects were also screened using the smartphone app “Epilepsy Diagnosis Aid”. Subjects screened positive at stage II underwent a complete neurological examination to confirm the diagnosis (stage III). Due to the COVID‐19 lockdown, some subjects have been evaluated through a digital platform (Zoom®). Results One‐thousand two‐hundred and thirteen interviews were performed at stage I, corresponding to a total screened population of 6692 inhabitants. Thirty‐eight screened positive were identified at stage I and II and of these, 28 people with epilepsy were identified, giving an overall prevalence of 4.2/1000 (95% CI 2.6–5.7). Prevalence rate steeply increased with age reaching a peak of 7.9/1000 in the population aged 20–29 years without significant differences between women and men. For almost 50% of the screened positive subjects, confirmation of epilepsy by a neurologist at stage III was achieved through simple videoconsultation. After a simultaneous awareness campaign, 22 self‐reported PWE requested a consultation and, among them, 11 had a diagnosis of epilepsy confirmed. Significance This study shows a prevalence estimate close to those reported for LMIC. Simple videoconsultation and specific apps may be valuable tools in epidemiological research. Awareness campaigns are important allies for a full case identification, particularly in contexts where higher rates of stigma are recorded.

Abstract This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose‐finding, international, multicenter, randomized, parallel‐group, endoscopist‐blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T0), 1 h (T1), 2 h (T2), 4 h (T4), and 8 h (T8) after completion of mannitol self‐administration. The mean mannitol plasma concentrations (mg/ml) were dose‐dependent with a consistent difference among doses. The mean maximum concentration (Cmax) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC0−∞) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in Cmax, AUC0−t8, and AUC0−∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects.

Abstract The explosive activity of the 2021 Tajogaite eruption eludes pigeonholing into well‐defined eruption styles, with a variety of pyroclast ejection modes occurring both alternately and simultaneously at multiple vents. Visually, we defined four endmembers of explosive activity, referred to as fountaining, spattering, ash‐poor jets and ash‐rich jets. To capture the physical parameters of these activities, we deployed a camera array including one high‐speed camera and three high‐definition cameras in two field campaigns. Transitions between and fluctuations within activity occurred at the time scale of minutes to hours, likely driven by the same shallow conduit and vent processes controlling Strombolian activity at other volcanoes, but at higher gas and magma fluxes. From a physical standpoint, mean pyroclast rise velocity ranged 5–50 m/s, maximum ejection velocity 10–220 m/s, and sub‐second mass flux of lapilli to bomb‐sized pyroclasts at the vent 0.2–200 × 103 kg/s. The largest mass flux occurred during fountaining, which contributed by far more than other activities to cone building. All explosive activity exhibited well‐defined pyroclast ejection pulses, and we found a positive correlation between the occurrence rate of ejection pulses and maximum pyroclast ejection velocity. Despite orders of magnitude variations, physical parameters shift gradually with no boundary from one activity endmember to another. As such, attributing this explosive activity specifically to any currently defined style variations is arbitrary and potentially misleading. The highly variable explosive activity of the Tajogaite eruption recalls previous definitions of violent Strombolian eruptions, an eruption style whose pyroclast ejection dynamics, however, were so far largely undefined.

Abstract In microwave device and circuit design, many simulations are often needed to find a set of designs that satisfy one or multiple specifications chosen by the designer upfront: the feasible region. A novel Bayesian active learning framework is presented to accurately identify the feasible region with a low number of simulations. The technique leverages on a stochastic model to obtain an efficient and automated procedure. A suitable application example validates the proposed technique and shows its effectiveness to rapidly obtain many suitable designs.

Abstract Europe has a well‐established network of breeding bird monitoring that is used to produce supranational indices of population trends for many species. However, a comparison of breeding bird censuses with other methods may be beneficial to confirm the validity of such indices. The aim of this study was to assess the value of standardized capture data of migratory birds at migration bottlenecks as an indicator of the effective breeding populations. One limitation to this method is that several populations are co‐occurring at these bottlenecks and their catchment areas need to be clearly identified to allow extrapolation of population indices. Here, we used standardized trends in capture numbers of 30 species on the island of Ponza, a migration bottleneck in the central Mediterranean, and compared them to population trends estimated in the putative catchment breeding areas between 2005 and 2016. The catchment areas were identified through the analysis of ring recoveries during the breeding season of birds passing through Ponza. Our results show an agreement between the population trends observed on Ponza and those in the breeding areas in 15 out of 30 species. The correlations were strongest in species with a more robust definition of the catchment areas, that is, species with more than 10 recoveries, and for which the recoveries were most likely of breeding birds. The main reason for disagreement between the two indices in the remaining species might be related to different intensity of sampling in different areas. This issue can be solved by further developing monitoring projects in underrepresented countries, as well as by intensifying monitoring through ringing, both in the breeding grounds and at migration bottlenecks. These results show that spring migration monitoring at bottlenecks has the potential to provide a valuable complement and an independent control of breeding bird surveys, allowing raising early warnings of population declines and contributing to their conservation.

Abstract Complex vector fitting (CVF) is a robust method to efficiently and accurately model general linear and passive baseband systems. Such models are important for the analysis and design of modern electronic and optical communication systems. This letter introduces an efficient toolbox implementation of the CVF algorithm. The effectiveness of the code is illustrated on a suitable application example.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia type in which the genetic alterations influencing the clinico‐biological course are not entirely understood. CLL has a heterogeneous course, with some patients showing an indolent course and others experiencing an aggressive course. Whole‐genome sequencing and whole‐exome sequencing studies identified recurrently mutated genes in CLL and profiled its clonal evolution patterns. However, more recent whole‐genome sequencing studies also identified variants in non‐coding sequences of the CLL genome, revealing important lesions outside the protein‐coding regions. Here we describe the most representative non‐coding lesion of the CLL genome, including lesions in the 3′‐UTR region of NOTCH1 which result in the truncation of the NOTCH1 protein PEST domain, and non‐coding mutations in an enhancer region on chromosome 9p13 which result in reduced expression of the PAX5 transcription factor. In addition, we describe the role of microRNA in CLL, in particular the miR15a/miR16‐1 microRNA recurrently affected by deletions of chromosome 13q14. Together, new findings in non‐coding genome genetic lesions provide a more complete portrait of the genomic landscape of CLL with clinical implications.

Abstract European Turtle Doves (Streptopelia turtur) are long‐distance migrants and have experienced a population decline of more than 78% since 1980. Their conservation depends on refined knowledge of breeding origins and population connectivity. Feathers collected at stopover sites, but molted at breeding grounds, provide an opportunity to assign birds to potential regions of origin using tissue stable hydrogen isotope values and relate those to a European feather hydrogen isoscape. Here, 101 feather samples from 13 different breeding countries were analyzed to calibrate the European hydrogen isoscape and 101 feather samples from Spanish, Italian, Maltese, Greek, and Bulgarian stopovers were assigned to potential regions of origin. The assigned range of origin for all 101 individuals grouped together agreed with known distribution patterns. Bulgarian samples were mostly assigned to Russian areas. Possible origins of Greek, Italian, Maltese, and Spanish samples ranged from central to southern Europe. Individual assignments highlighted four broad regions of origin, corresponding to a cool/humid to hot/dry temperature gradient. Proportions of birds assigned to these regions varied among birds sampled at different stopover sites. Therefore, our results provide important information about population connectivity and may be useful to evaluate possible influences of hunting on Turtle Dove populations.

Abstract Introduction There is conflicting evidence whether high‐density lipoprotein cholesterol (HDL‐C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL‐C. We aimed to assess AD risk by genetically predicted HDL‐C. Methods Ten single nucleotide polymorphisms within the CETP locus predicting HDL‐C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR‐Egger. Results Based on 10 single nucleotide polymorphisms distinctly predicting HDL‐C in the CETP locus, we found that HDL‐C was not associated with risk of AD (P > .7). Discussion Our study does not support the role of HDL‐C on risk of AD through HDL‐C altered by CETP. This study does not rule out other mechanisms by which HDL‐C affects risk of AD.