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We present the serendipitous radio-continuum discovery of a likely Galactic supernova remnant (SNR) G305.4–2.2. This object displays a remarkable circular symmetry in shape, making it one of the most circular Galactic SNRs known. Nicknamed Teleios due to its symmetry, it was detected in the new Australian Square Kilometre Array Pathfinder (ASKAP) Evolutionary Map of the Universe (EMU) radio–continuum images with an angular size of 1 320$^{\prime\prime}$$\times$1 260$^{\prime\prime}$ and PA = 0$^\circ$. While there is a hint of possible H$\alpha$ and gamma-ray emission, Teleios is exclusively seen at radio–continuum frequencies. Interestingly, Teleios is not only almost perfectly symmetric, but it also has one of the lowest surface brightnesses discovered among Galactic SNRs and a steep spectral index of $\alpha$=–0.6$\pm$0.3. Our best estimates from Hi studies and the $\Sigma$–D relation place Teleios as a type Ia SNR at a distance of either $\sim$2.2 kpc (near-side) or $\sim$7.7 kpc (far-side). This indicates two possible scenarios, either a young (under 1 000 yr) or a somewhat older SNR (over 10 000 yr). With a corresponding diameter of 14/48 pc, our evolutionary studies place Teleios at the either early or late Sedov phase, depending on the distance/diameter estimate. However, our modelling also predicts X-ray emission, which we do not see in the present generation of eROSITA images. We also explored a type Iax explosion scenario that would point to a much closer distance of $\lt$1 kpc and Teleios size of only $\sim$3.3 pc, which would be similar to the only known type Iax remnant SN1181. Unfortunately, all examined scenarios have their challenges, and no definitive Supernova (SN) origin type can be established at this stage. Remarkably, Teleios has retained its symmetrical shape as it aged even to such a diameter, suggesting expansion into a rarefied and isotropic ambient medium. The low radio surface brightness and the lack of pronounced polarisation can be explained by a high level of ambient rotation measure (RM), with the largest RM being observed at Teleios’s centre.
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.
In April 2023, eighteen scholars from nine different subjects representing the humanities, natural and social sciences came together for a one-day workshop at St John’s College, Durham. Despite our differences, all had one aim: the study of past environmental change and its effects on human societies. Talking across disciplinary divides, we discussed what environmental history is, how it may or may not contribute to tackling the climate crisis, and the problems of sources, scale and temporality. This article collects select conversations into a roundtable format split into four areas: scale, time and space, interdisciplinarity, and the future of environmental history. We argue that environmental history is more usefully understood not as a distinct sub-field of history, but as an interdisciplinary meeting place for innovative collaboration. This also presents a model for future research aimed at tackling the climate crisis at higher education institutions.
This chapter provides an up-to-date review of the literature on the phonetic and phonological patterns of Welsh and their development. While typically developing children’s acquisition constitutes a major component, it also discusses socio-phonetic variation and adult second language acquisition, thereby approaching Welsh speech development from a lifespan perspective. The chapter is structured in four major sections. The first section introduces the reader to the segmental and suprasegmental properties of the two main varieties of Welsh: Northern and Southern Welsh. Subsequently, the second section considers methodological aspects of studies on Welsh phonology, while the third section focuses on children’s development of Welsh speech patterns, starting with evidence from studies on early word productions before moving on to a discussion of consonant and consonant cluster acquisition in preschool and school-aged children. The section concludes with an account of developmental error patterns. The final major section then reviews the literature on the speech patterns of different groups of Welsh speakers and the role that extra-linguistic variables, such as sex/gender and language dominance, play in shaping these. Finally, studies on the Welsh accents of second language learners will be discussed. The chapter concludes with suggestions for future research.
We recently reported that cultural group membership may be a predictor of the likelihood that an individual will detect a faked accent in a recording. Here, we present follow-up data to our original study using a larger data set comprised of responses from the across the world. Our findings are in line with our previous work and suggest that native listeners perform better at this task than do non-native listeners overall, although with some between-group variation. We discuss our findings within the context of signals of trustworthiness and suggest future avenues of research.
Distinguishing early domesticates from their wild progenitors presents a significant obstacle for understanding human-mediated effects in the past. The origin of dogs is particularly controversial because potential early dog remains often lack corroborating evidence that can provide secure links between proposed dog remains and human activity. The Tumat Puppies, two permafrost-preserved Late Pleistocene canids, have been hypothesized to have been littermates and early domesticates due to a physical association with putatively butchered mammoth bones. Through a combination of osteometry, stable isotope analysis, plant macrofossil analysis, and genomic and metagenomic analyses, this study exploits the unique properties of the naturally mummified Tumat Puppies to examine their familial relationship and to determine whether dietary information links them to human activities. The multifaceted analysis reveals that the 14,965–14,046 cal yr BP Tumat Puppies were littermates who inhabited a dry and relatively mild environment with heterogeneous vegetation and consumed a diverse diet, including woolly rhinoceros in their final days. However, because there is no evidence of mammoth consumption, these data do not establish a link between the canids and ancient humans.
Previous observational studies suggested that vitamin D may control the absorption of iron (Fe) by inhibition of hepcidin, but the causal relevance of these associations is uncertain. Using placebo-controlled randomisation, we assessed the effects of supplementation with vitamin D on biochemical markers of Fe status and erythropoiesis in community-dwelling older people living in the UK. The BEST-D trial, designed to establish the optimum dose of vitamin D3 for future trials, had 305 participants, aged 65 years or older, randomly allocated to 4000 IU vitamin D3 (n 102), 2000 IU vitamin D3 (n 102) or matching placebo (n 101). We estimated the effect of vitamin D allocation on plasma levels of hepcidin, soluble transferrin receptor (sTfR), ferritin, Fe, transferrin, saturated transferrin (TSAT%) and the sTfR–ferritin index. Despite increases in 25-hydroxy-vitamin D, neither dose had significant effects on biochemical markers of Fe status or erythropoiesis. Geometric mean concentrations were similar in vitamin D3 arms v. placebo for hepcidin (20·7 [se 0·90] v. 20·5 [1·21] ng/ml), sTfR (0·69 [0·010] v. 0·70 [0·015] µg/ml), ferritin (97·1 [2·81] v. 97·8 [4·10] µg/l) and sTfR–ferritin ratio (0·36 [0·006] v. 0·36 [0·009]), respectively, while arithmetic mean levels were similar for Fe (16·7 [0·38] v. 17·3 [0·54] µmol/l), transferrin (2·56 [0·014] v. 2·60 [0·021] g/dl) and TSAT% (26·5 [0·60] v. 27·5 [0·85]). The proportions of participants with ferritin < 15 µg/l and TSAT < 16 % were unaltered by vitamin D3 suggesting that 12 months of daily supplementation with moderately high doses of vitamin D3 are unlikely to alter the Fe status of older adults.
Through compositional inclusion or exclusion, the photograph can assert and communicate what belongs in a picture, in a landscape, in an ecosystem. It can illuminate what we deem conservation-worthy, or, on a larger scale, which extinctions are attention-worthy. Photographic practice helps to illuminate the active nature of extinction, and our choices as actors and witnesses within that process. Here, researchers from the University of Leeds’ Extinction Studies Doctoral Training Programme present individual reflections on interdisciplinary practice-led research in the Scottish Small Isles. We consider how photography, as a form of praxis, can generate new forms of knowledge surrounding extinction: its meanings, representations, and legacies, particularly through visual representation. We offer seven perspectives on contemporary image-making, from disciplines including philosophy, conservation biology, literature, sociology, geology, cultural anthropology, and palaeontology. Researchers gathered experiential, ethical, even biological meanings from considering what to include or exclude in images: from the micro to the macro, the visible to the invisible, the aesthetic to the ecological. We draw conclusions around meaning-making through the process of photography itself, and the tensions encountered through framing and decision-making in a time of mass ecological decline.
Studies show stimulant medications are effective for different ADHD presentations (predominantly inattentive [IA], predominantly hyperactive-impulsive [HI] or combined [C]); however, few studies have evaluated nonstimulant efficacy in different ADHD presentations. Viloxazine ER [VLX ER] is a nonstimulant, FDA-approved medication for pediatric (≥6 yrs) and adult ADHD. This post-hoc analysis of 4 double-blind (DB), Phase 3, clinical trials (2 in adolescents [NCT03247517 and NCT03247556], 2 in children [NCT03247530 and NCT03247543]), evaluates VLX ER efficacy by ADHD presentation as derived from ADHD Rating Scale, 5th Edition (ADHD-RS-5) assessments at Baseline.
Methods
Children and adolescents with ADHD and an ADHD-RS-5 Total score ≥ 28 were eligible for enrollment. ADHD presentation was defined as a rating of ≥2 on at least 6 of 9 ADHD-RS-5 inattention items, or hyperactive-impulsive items or both. For each ADHD presentation, the change from Baseline (CFB) in ADHD-RS-5 Total score (primary outcome in each study) was assessed using mixed models for repeated measures (MMRM). Responder rate (secondary outcome), ≥50% reduction from baseline in ADHD-RS-5 Total score, was analyzed using generalized estimating equations (GEE).
Results
Of 1354 subjects [placebo N = 452, VLX ER N = 902], ADHD presentation was assigned as 288 (21.3%) [IA], 1010 (74.5%) [C], 40 (3.0%) [HI], 16 (1.2%) [none of these]. Due to the small sample size of [HI], only the [IA] and [C] results are presented. At Week 6 (pooled data endpoint), ADHD-RS-5 Total scores were significantly improved for VLX ER relative to placebo for both the [IA] and [C] ADHD presentations. LS mean (SE) treatment differences, p-values were: [IA] -3.1 (1.35), p = 0.0219, and [C] 5.8 (0.97), p < 0.0001. Responder rates were also significantly higher for VLX ER: 43.0% [IA] and 42.7% [C] relative to placebo 29.5% [IA] and 25.5 % [C] (p=.0311 and p<.0001).
Conclusions
Viloxazine ER significantly reduced ADHD symptoms in individuals meeting criteria for ADHD [IA] or [C] presentations at Baseline. Limitations include post-hoc methodology, smaller sample sizes of [IA] and [HI] groups, and the ADHD-RS-5 ≥ 28 eligibility requirement, that may favor enrollment of individuals with ADHD [C] over ADHD [IA] or [HI] presentations. Consistency of response during long-term use should be evaluated.
Viloxazine ER (extended-release capsules; Qelbree®) is a nonstimulant medication, FDA-approved for ADHD in children (≥6 years) and adults. Efficacy and safety for children and adolescents were evaluated in one phase 2 [NCT02633527]and four phase 3 [NCT03247517, NCT03247556, NCT03247530, and NCT03247543], double-blind (DB), placebo-controlled trials that fed into a long-term, open-label extension (OLE) trial [NCT02736656]. Here we report the findings from this OLE trial.
Methods
Participants completing the DB trials were eligible for the OLE. Viloxazine ER was initiated at 100 mg/day (children) or 200 mg/day (adolescents) and adjusted (if needed) over a 12-week Dose-Optimization Period (up to 400 mg/day [children] or 600 mg/day [adolescents]). Maintenance treatment then continued up to 72 months. Safety assessments included adverse events (AEs), clinical laboratory tests, vital signs, ECG (12-lead), and the Columbia Suicide Severity Rating Scale (C-SSRS). Efficacy assessments included the ADHD Rating Scale, 4th (Phase 2) or 5th (Phase 3) Edition (ADHD-RS-IV/5), and the Clinical Global Impression-Improvement (CGI-I) scale. Efficacy was assessed relative to DB baseline at study visits ˜ 3 months apart. Two response measures, 50% improvement in ADHD-RS-IV/5 Total score and CGI-I score of 1-2, were also evaluated.
Results
1100 individuals (646 children; 454 adolescents; 66.5% male/33.5% female) received treatment. Median (range) exposure to viloxazine ER was 260 (1 to 1896) days. AEs were reported by 57.3% participants, most commonly (≥5%) nasopharyngitis (9.7%), somnolence (9.5%), headache (8.9%) decreased appetite (6.0%), and fatigue (5.7%). AEs were mostly mild or moderate in severity (3.9% reported any severe AE); AEs led to viloxazine ER discontinuation for 8.2%. The mean (SD) changes from DB baseline in ADHD-RS IV/5 Total score were -17.0 (14.18) (viloxazine ER) and -11.2 (13.19) (placebo) at the last DB study visit, 24.3 (11.96) at OLE Month 3, and 22.4 (13.62) at participants’ last OLE study visit. ADHD-RS-IV/5 and CGI-I responder rates each exceeded 65% at all OLE visits following Dose-Optimization.
Conclusions
The safety and efficacy of viloxazine ER were maintained with long-term use in children and adolescents with ADHD. No new safety concerns emerged, and efficacy results suggested potential for continued improvement over that seen during DB treatment.
This paper uses log-linear models with latent variables (Hagenaars, in Loglinear Models with Latent Variables, 1993) to define a family of cognitive diagnosis models. In doing so, the relationship between many common models is explicitly defined and discussed. In addition, because the log-linear model with latent variables is a general model for cognitive diagnosis, new alternatives to modeling the functional relationship between attribute mastery and the probability of a correct response are discussed.
We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.
This chapter provides a thorough, up-to-date review of the literature on the phonetics and phonology of early bilinguals. It pulls together studies from a range of bilingual settings, including bilingual societies and heritage language contexts. While the chapter mostly reviews evidence from adolescent and adult participants, it also makes reference to the child bilingualism literature, where appropriate. The chapter first reviews studies on the accents of early versus late bilinguals, followed by a discussion of the various explanatory accounts for the observed differences between these two groups. Subsequently, the critical significance of early linguistic experience on bilingual speech patterns is considered, with particular reference to the evidence from childhood overhearers and international adoptees. The following sections then review studies comparing simultaneous and early sequential bilinguals, and those exploring the role of language dominance, continued use, the language of the environment in bilinguals’ pronunciation patterns, and the role of sociolinguistic factors in early bilingual speech patterns. The chapter concludes with suggestions for future research.
Previous research in the evolutionary and psychological sciences has suggested that markers or tags of ethnic or group membership may help to solve cooperation and coordination problems. Cheating remains, however, a problem for these views, insofar as it is possible to fake the tag. While evolutionary psychologists have suggested that humans evolved the propensity to overcome this free rider problem, it is unclear how this module might manifest at the group level. In this study, we investigate the degree to which native and non-native speakers of accents – which are candidates for tags of group membership – spoken in the UK and Ireland can detect mimicry. We find that people are, overall, better than chance at detecting mimicry, and secondly we find substantial inter-group heterogeneity, suggesting that cultural evolutionary processes drive the manifestations of cheater detection. We discuss alternative explanations and suggest avenues of further inquiry.
The increased severity and frequency of bushfires accompanying human-induced global warming have dire implications for biodiversity conservation. Here we investigate the response of a cryptic, cool-climate elapid, the mustard-bellied snake Drysdalia rhodogaster, to the extensive Black Summer fires of 2019/2020 in south-eastern Australia. The species is categorized as Least Concern on the IUCN Red List (last assessed in 2017), but because a large part of its range was burnt during the Black Summer and little was known about its ecology, D. rhodogaster was identified as a priority species for post-fire impact assessment. We evaluated three lines of evidence to assess the impact of the Black Summer fires on D. rhodogaster. Habitat suitability modelling indicated that c. 46% of the predicted range of the species was affected by bushfire. Field surveys conducted 9–36 months post-fire and collation of records from public databases submitted 0–24 months post-fire indicated that D. rhodogaster persisted in burnt landscapes. Fire severity and proportion of the landscape that was burnt within a 1,000-m radius of survey sites were poor predictors of site occupancy by D. rhodogaster. Although conclusions regarding the effects of fire on D. rhodogaster are limited because of the lack of baseline data, it is evident that the species has persisted across the landscape in the wake of extensive bushfires. Our work highlights the need for baseline knowledge on cryptic species even when they are categorized as Least Concern, as otherwise assessments of the impacts of catastrophic events will be constrained.
Studies of extinction typically focus on unintended losses of biodiversity and culture. This study, however, examines an attempt to induce extinction of a parasite: human hookworm (Necator americanus and Ancylostoma duodenale). Our interdisciplinary approach integrates medical history and epidemiology using records created by the Jamaica Hookworm Commission of 1919–1936. We show that the attempt to induce the extinction of hookworms was driven by its perceived effects on labour productivity and consequent status as an ideological and economic threat. We use spatial epidemiology to describe the relationships between parasites, environments and the working conditions of plantation labourers. Using data from 330 locations across Jamaica in which 169,380 individuals were tested for hookworm infection we show that the prevalence of hookworm infection was higher in districts surrounding plantations. Prevalence decreased with the temperature of the coldest month, increased with the amount of rainfall in the driest month, and increased with vegetation quantity (normalised difference vegetation index). Worm burden (and thus pathology) varied greatly between individuals, even those living together; hookworm infection varied between environments, socioeconomic conditions and individuals. Nevertheless, the conditions of labour shaped the distribution of hookworms. Plantations both spread and problematised hookworms, driving efforts to bring it to extinction.
Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring.
Aims
To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK.
Method
We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment.
Results
We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally.
Conclusions
Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.
The focus on social determinants of health (SDOH) and their impact on health outcomes is evident in U.S. federal actions by Centers for Medicare & Medicaid Services and Office of National Coordinator for Health Information Technology. The disproportionate impact of COVID-19 on minorities and communities of color heightened awareness of health inequities and the need for more robust SDOH data collection. Four Clinical and Translational Science Award (CTSA) hubs comprising the Texas Regional CTSA Consortium (TRCC) undertook an inventory to understand what contextual-level SDOH datasets are offered centrally and which individual-level SDOH are collected in structured fields in each electronic health record (EHR) system potentially for all patients.
Methods:
Hub teams identified American Community Survey (ACS) datasets available via their enterprise data warehouses for research. Each hub’s EHR analyst team identified structured fields available in their EHR for SDOH using a collection instrument based on a 2021 PCORnet survey and conducted an SDOH field completion rate analysis.
Results:
One hub offered ACS datasets centrally. All hubs collected eleven SDOH elements in structured EHR fields. Two collected Homeless and Veteran statuses. Completeness at four hubs was 80%–98%: Ethnicity, Race; < 10%: Education, Financial Strain, Food Insecurity, Housing Security/Stability, Interpersonal Violence, Social Isolation, Stress, Transportation.
Conclusion:
Completeness levels for SDOH data in EHR at TRCC hubs varied and were low for most measures. Multiple system-level discussions may be necessary to increase standardized SDOH EHR-based data collection and harmonization to drive effective value-based care, health disparities research, translational interventions, and evidence-based policy.
Normal pressure hydrocephalus (NPH) is characterized by pathologically enlarged ventricles without elevated cerebrospinal fluid (CSF) pressure along with a triad of clinical symptoms including gait disturbances, urinary incontinence, and cognitive impairment. NPH is evaluated with lumbar drain trials (LDTs) where CSF is removed over several days to determine if patients would benefit from ventricular shunting. Candidate selection and success for these surgeries remains challenging because other diseases such as Alzheimer’s disease (AD) share common features with NPH in cognitive impairment and enlarged ventricles. Prior research has found that 20%-40% of presumed NPH cases have AD pathology as determined by brain biopsy or autopsy. CSF biomarkers of AD can be altered in NPH and are not always conclusive, complicating the interpretation of results when formulating diagnoses and prognoses. Studies to refine the analyses of AD CSF biomarkers in NPH are needed. We aimed to examine the frequency of CSF biomarker results among patients presenting for NPH evaluations with LDTs.
Participants and Methods:
62 patients presented for LDTs upon physician recommendations. CSF specimens were sent to Mayo Clinic Laboratories for Alzheimer Disease Evaluation (ADEVL) that utilizes Elecsys (Lenexa, KS) CSF electrochemiluminescence immunoassays (Roche Diagnostics, Basel, Switzerland) to measure levels of amyloid-beta 42 (Aβ42), total tau (t-tau), and phosphorylatedtau (p-tau), and p-tau:Aβ42 ratio. Results were classified based on interpretation through the Amyloid/Tau/Neurodegeneration (ATN) framework1: 1) AD - biomarker profile consistent with AD pathologic change, 2) non-AD profile - biomarker levels normal or inconsistent with AD pathologic change, or 3) indeterminate - biomarkers were incongruous with only one or two abnormal levels of Aβ42, t-tau, p-tau, or ptau: Aβ42. Indeterminate cases may represent altered protein levels due to CSF dynamics or AD-related pathologic change. In reviewing recent research on CSF dynamics and AD biomarkers in NPH2 a p-tau threshold of 15 pg/mL was derived and implemented such that cases with Aß42 <=1026 pg/mL and p-tau <15 pg/mL were designated as suspected non-AD, and those with Aß42 <=1026 pg/mL and p-tau >15 pg/mL were designated suspected AD.
Results:
Of the 62 LDT cases, 12 (19.35%) were classified as AD, 31 (50%) were indeterminate and 22 (35.48%) were non-AD. Of the 31 indeterminate cases, 21 (33.87% of the overall sample) were suspected non-AD and 7 (11.29% of the full sample) were categorized as suspected AD.
Conclusions:
Our findings show that 20%-30% of patients presenting for LDT showed evidence for AD-type pathologic change, consistent with prior reports of AD pathology in cases of possible NPH. Half of all LDT cases had indeterminate AD CSF biomarker results, the interpretations of which were confounded by the potential alterations of CSF biomarkers levels due to NPH independent of AD. Our findings emphasize the need to establish better approaches to interpreting CSF AD biomarkers in evaluating NPH. Future research should examine the discriminative utility of CSF AD biomarkers and the selected p-tau threshold in indeterminate cases for predicting response to LDT and shunting.