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This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer’s disease (AD) research sample.
The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models.
A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory.
The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition.
Cow’s milk allergy (CMA) is the most common food allergy in young children and it is often the first manifestation of atopic diseases. Accordingly, very early environmental factors, such as maternal diet during pregnancy, may play a role in the development of CMA, but the evidence is limited. The aim of this study was to investigate the association between maternal intake of antioxidant nutrients during pregnancy and the subsequent development of CMA in the offspring in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Maternal dietary information during pregnancy was collected with a detailed, validated food frequency questionnaire. The maternal dietary information and the information on putative confounding factors was available for 4403 children. Information on diagnosed CMA (n=448), was obtained from a medical registry and queried from the parents up to child’s age of 3 years. The Finnish food composition database was used to calculate the average daily intake of nutrients. Logistic regression was applied for statistical analyses, and the nutrient intakes were adjusted for energy intake. Odds ratios are presented per one standard deviation increment of the particular nutrient intake. Maternal total and dietary intake of beta-carotene was associated with an increased risk of CMA in the offspring when adjusted for the putative confounding factors (total: OR 1.10 95% CI 1.02-1.20, dietary: OR 1.10 95% CI 1.01-1.19). Using dietary supplements containing antioxidants in addition to a balanced diet may not confer any additional benefits.
Alexithymia is a personality construct characterized by difficulties in identifying and verbalizing feelings, a restricted imagination, and an externally oriented thinking style. As alexithymia shows marked overlap with depression, its independent nature as a personality construct is still being debated. The etiology of alexithymia is unknown, although childhood emotional neglect and attachment formation are thought to play important roles. In the FinnBrain Birth Cohort Study, experiences of early-life adversities (EA) and childhood maltreatment (CM) were studied in a sample of 2,604 men and women. The overlap and differences between depression and alexithymia were investigated by comparing their associations with EA types and adult attachment style. Alexithymia was specifically associated with childhood emotional neglect (odds ratio (OR) 3.8, p < .001), whereas depression was related to several types of EA. In depression co-occurring with alexithymia, there was a higher prevalence of emotional neglect (81.3% vs. 54.4%, p < .001), attachment anxiety (t = 2.38, p = .018), and attachment avoidance (t = 4.03, p < .001). Early-life adversities were markedly different in the alexithymia group compared to those suffering from depression, or healthy controls. Depression with concurrent alexithymia may represent a distinct subtype, specifically associated with childhood experiences of emotional neglect, and increased attachment insecurity compared to non-alexithymic depression.
Cluster analyses have become popular tools for data-driven classification in biological psychiatric research. However, these analyses are known to be sensitive to the chosen methods and/or modelling options, which may hamper generalizability and replicability of findings. To gain more insight into this problem, we used Specification-Curve Analysis (SCA) to investigate the influence of methodological variation on biomarker-based cluster-analysis results.
Proteomics data (31 biomarkers) were used from patients (n = 688) and healthy controls (n = 426) in the Netherlands Study of Depression and Anxiety. In SCAs, consistency of results was evaluated across 1200 k-means and hierarchical clustering analyses, each with a unique combination of the clustering algorithm, fit-index, and distance metric. Next, SCAs were run in simulated datasets with varying cluster numbers and noise/outlier levels to evaluate the effect of data properties on SCA outcomes.
The real data SCA showed no robust patterns of biological clustering in either the MDD or a combined MDD/healthy dataset. The simulation results showed that the correct number of clusters could be identified quite consistently across the 1200 model specifications, but that correct cluster identification became harder when the number of clusters and noise levels increased.
SCA can provide useful insights into the presence of clusters in biomarker data. However, SCA is likely to show inconsistent results in real-world biomarker datasets that are complex and contain considerable levels of noise. Here, the number and nature of the observed clusters may depend strongly on the chosen model-specification, precluding conclusions about the existence of biological clusters among psychiatric patients.
In methodical product development, numerous data are used and linked with each other, especially variant-related data. This paper presents a model-based solution for avoiding inconsistencies in the development of product families with many variants and extends it to modular lightweight design. In addition, the inconsistencies in methodical product development were classified and solution approaches were shown. Thus, inconsistencies can be avoided with the presented elaborated data model for an integrated product and process model based on the presented procedure.
OBJECTIVES/GOALS: Neuroblastoma (NB) is the most common extra-cranial solid tumor with outcomes varying from spontaneous regression to metastatic with high mortality rates. The tumor immune microenvironment (TIME) may play a significant role in this disease. In this study we analyze the TIME comparing high-risk (HR) and low-risk (LR) NBs using multiplex platforms. METHODS/STUDY POPULATION: Two tissue microarrays (TMAs) with 2mm cores were created from 41 patients treated at Columbia University Irving Medical Center. Five micron TMA slides were stained for Digital Spatial Profiling (DSP, nanoString) and multiplex immunofluorescence (mIF). For DSP, a 24-patient subset including 11 HR, 8 LR and 4 intermediate risk patients was analyzed for 34 proteins. Protein expression among risk groups was compared using Mann-Whitney t-test. For mIF, TMA FFPE slides were stained for DAPI, CD3, CD8, CD68, HLA-DR, PDL1 and Chromogranin A. Whole TMA cores were captured as 9 -20X multispectral images (MSIs) stitched into a 3x3 MSI using Vectra (Akoya). MSIs were processed with inForm and qualitative analysis performed comparing HR and LR tumors. RESULTS/ANTICIPATED RESULTS: With DSP, we find significantly more HLA-DR in HR compared to LR tumors (p = 0.016). When controlling for immune cells with CD45 we find HLA-DR/CD45 to be higher in HR than LR tumors (p = 0.026). We found increased PD1 and PDL1 expression in all groups without significant difference between LR and HR (p = 0.778 and p = 0.310, respectively). Preliminary analysis of mIF on 9 patients (4 HR and 5 LR) finds HR tumors appear to have more immune cells than LR tumors, specifically more CD3+CD8- T cells while total CD8+ cells may be similar. There may be less macrophages in the HR compared to LR tumors. Completion of image processing and quantitative analysis of mIF data is underway. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased expression of immune markers in NB TIME correlates with higher risk, which is unlike many other tumors. We compared TIME in HR and LR NB using multiplex platforms, DSP and mIF. We find that HLA-DR is more expressed in HR NB while PD1 and PDL1 expression is consistently high and not different between risk groups. Further analysis is underway. CONFLICT OF INTEREST DESCRIPTION: Robyn D. Gartrell-Corrado received grant support from nanoString for Digital Spatial Profiling and received honoraria and travel support from Northwest Biotherapeutics and PerkinElmer, respectively.
Biomagnetic field sensors based on AlN/FeCoSiB magnetoelectric (ME) composites desire a resonant frequency that can be precisely tuned to match the biomagnetic signal of interest. A tunable mechanical resonant frequency is achieved when ME composites are integrated onto shape memory alloy (SMA) thin films. Here, high-quality c-axis growth of AlN is obtained on (111) Pt seed layers on both amorphous and crystallized TiNiCu SMA thin films on Si substrates. These composites show large piezoelectric coefficients as high as d33,f= 6.4 pm/V ± 0.2 pm/V. Annealing the AlN/Pt/Ta/amorphous TiNiCu/Si composites to 700 °C to crystallize TiNiCu promoted interdiffusion of Ti into the Ta/Pt layers, leading to an enhanced conductivity in AlN. Depositing AlN onto already crystalline TiNiCu films with low surface roughness resulted in the best piezoelectric films and hence is found to be a more desirable processing route for ME composite applications.
This paper develops the idea that nosological reform is ultimately a matter of finding homogeneous groups of patients that are maximally distinct from each other. The focus lies on the statistical properties of patients, so that the problem of classification coincides with the problem of the reference class from the philosophy of science. It is argued that specific statistical methods – model selection and causal modeling – can assist in finding good classifications. An important advantage of these statistical methods is that they do not favor any particular explanatory level or vocabulary. Whether or not we should include some patient characteristic in our classification scheme is an empirical issue, to be settled entirely by its contribution to the performance of the scheme in predictions and intervention decisions. For this reason the paper adopts a so-called a-reductionist perspective: we do not need a principled discussion on reductionism.
Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression.
Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n ≈ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS).
Estimates of current and lifetime MDD prevalence were 6.7% and 18.1%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95% CI 1.15–1.32, R2 = 1.47%).
By assessing MDD status in the Netherlands using the LIDAS instrument, we were able to confirm previously reported MDD prevalence and heritability estimates, which suggests that this instrument can be used in epidemiological and genetic association studies of depression.
Several prospective studies have shown an association between cows’ milk consumption and the risk of islet autoimmunity and/or type 1 diabetes. We wanted to study whether processing of milk plays a role. A population-based birth cohort of 6081 children with HLA-DQB1-conferred risk to type 1 diabetes was followed until the age of 15 years. We included 5545 children in the analyses. Food records were completed at the ages of 3 and 6 months and 1, 2, 3, 4 and 6 years, and diabetes-associated autoantibodies were measured at 3–12-month intervals. For milk products in the food composition database, we used conventional and processing-based classifications. We analysed the data using a joint model for longitudinal and time-to-event data. By the age of 6 years, islet autoimmunity developed in 246 children. Consumption of all cows’ milk products together (energy-adjusted hazard ratio 1·06; 95 % CI 1·02, 1·11; P = 0·003), non-fermented milk products (1·06; 95 % CI 1·01, 1·10; P = 0·011) and fermented milk products (1·35; 95 % CI 1·10, 1·67; P = 0·005) was associated with an increased risk of islet autoimmunity. The early milk consumption was not associated with the risk beyond 6 years. We observed no clear differences based on milk homogenisation and heat treatment. Our results are consistent with the previous studies, which indicate that high milk consumption may cause islet autoimmunity in children at increased genetic risk. The study did not identify any specific type of milk processing that would clearly stand out as a sole risk factor apart from other milk products.
Some species of gut bacteria produce short-chain fatty acids (SCFAs) from dietary fiber—mainly acetate, propionate, and butyrate. The composition of human gut microbiota is dependent on dietary intake and health status. The aim of this study was to assess the effect of diet and anthropometric parameters on the potential of gut microbiota to metabolize dietary fiber and produce SCFA.
A group of 200 men and women aged 31 to 50 years old participated in the study. The diet was assessed using three-day dietary records and the dietary pattern was determined using score methods. The potential to utilize water-insoluble fiber was assessed by measuring the β-glucosidase enzymatic activity of dissolved feces. To estimate the potential to metabolize water-soluble dietary fiber, cultures containing feces and pectin were incubated under anaerobic conditions for 24 hours. The amounts of fiber, acetic acid, propionic acid, and butyric acid before and after incubation were measured.
Pectin utilization correlated positively with the amount of energy intake from fat (r = 0.19) and with the intake of nuts and seeds (r = 0.17) and was negatively correlated with the amount of energy from complex carbohydrates (r = -0.16) and its sources, such as refined grain products (r = -0.15). The dietary pattern did not affect the potential of the gut microbiota to metabolize pectin, but did influence the potential to digest insoluble dietary fiber, as the subjects following the western dietary pattern had lower potential than those following the rational pattern. β-glucosidase activity correlated positively with the intake of dietary fiber (r = 0.19) and intake of its sources, such as fruits (r = 0.18), vegetables (r = 0.21), and nuts and seeds (r = 0.18); it correlated negatively with nonalcoholic beverage intake (r = -0.15) and sugar and honey intake (r = -0.16). The potential to synthesize acetic acid correlated negatively with dietary indices and dietary fiber intake (r = -0.18). The potential to synthesize propionic acid correlated negatively with hip and waist circumference (r = -0.14, -0.15, respectively). The potentials to synthesize both propionic and butyric acid were affected by the intake of nuts and seeds (r = 0.18, 0.21, respectively).
Diet affects the potential of gut microbiota to utilize dietary fiber and to produce SCFAs. The impact of anthropometry parameters was only seen on the potential to synthesize propionic acid.
Stictococcus vayssierei is a major pest of root and tuber crops in central Africa. However, data on its ecology are lacking. Here we provide an updated estimate of its distribution with the aim of facilitating the sustainable control of its populations. Surveys conducted in nine countries encompassing 13 ecological regions around the Congo basin showed that African root and tuber scale was present in Cameroon, Central African Republic, Congo, Democratic Republic of Congo, Equatorial Guinea, Gabon and Uganda. It was not found on the sites surveyed in Chad and Nigeria. The pest occurred in the forest and the forest-savannah mosaic as well as in the savannah where it was never recorded before. However, prevalence was higher in the forest (43.1%) where cassava was the most infested crop, compared to the savannah (9.2%) where aroids (cocoyam and taro) were the most infested crops. In the forest habitat, the pest was prevalent in all but two ecological regions: the Congolian swamp forests and the Southern Congolian forest-savanna mosaic. In the savannah habitat, it was restricted to the moist savannah highlands and absent from dry savannahs. The scale was not observed below 277 m asl. Where present, the scale was frequently (87.1% of the sites) attended by the ant Anoplolepis tenella. High densities (>1000 scales per plant) were recorded along the Cameroon–Gabon border. Good regulatory measures within and between countries are required to control the exchange of plant materials and limit its spread. The study provides information for niche modeling and risk mapping.
The design of government portfolios – that is, the distribution of competencies among government ministries and office holders – has been largely ignored in the study of executive and coalition politics. This article argues that portfolio design is a substantively and theoretically relevant phenomenon that has major implications for the study of institutional design and coalition politics. The authors use comparative data on portfolio design reforms in nine Western European countries since the 1970s to demonstrate how the design of government portfolios changes over time. Specifically, they show that portfolios are changed frequently (on average about once a year) and that such shifts are more likely after changes in the prime ministership or the party composition of the government. These findings suggest a political logic behind these reforms based on the preferences and power of political parties and politicians. They have major implications for the study of institutional design and coalition politics.
Network models block reductionism about psychiatric disorders only if models are interpreted in a realist manner – that is, taken to represent “what psychiatric disorders really are.” A flexible and more instrumentalist view of models is needed to improve our understanding of the heterogeneity and multifactorial character of psychiatric disorders.
Legionella pneumophila genotyping is important for epidemiological investigation of nosocomial and community-acquired outbreaks of legionellosis. The prevalence of legionellosis in pneumonia patients in the West Bank was monitored for the first time, and the sequence types (STs) from respiratory samples were compared with STs of environmental samples from different wards of the hospital. Sputum (n = 121) and bronchoalveolar lavage (BAL) (n = 74) specimens were cultured for L. pneumophila; genomic DNA was tested by 16S rRNA polymerase chain reaction (PCR) amplification. Nested PCR sequence-based typing (NPSBT) was implemented on DNA of the respiratory and environmental PCR-positive samples. Only one respiratory specimen was positive for L. pneumophila by culture. BAL gave a higher percentage of L. pneumophila-positive samples, 35% (26/74) than sputum, 15% (18/121) by PCR. NPSBT revealed the following STs: ST 1 (29%, 7/24), ST 461 (21%, 5/24), ST 1037 (4%, 1/24) from respiratory samples, STs from environmental samples: ST 1 (28.5%, 4/14), ST 187 (21.4%, 3/14) and ST 2070, ST 461, ST 1482 (7.1%, 1/14) each. This study emphasises the advantage of PCR over culture for the detection of L. pneumophila in countries where antibiotics are indiscriminately used prior to hospital admission. ST 1 was the predominant ST in both respiratory and environmental samples.
Meteorological parameters and air pollen count have been associated with affective disorders and suicide. Regarding peripartum depression, the literature is restricted and inconclusive.
This cross-sectional study included women (pregnant, n = 3843; postpartum, n = 3757) who participated in the BASIC (Biology, Affect, Stress, Imaging, and Cognition) study 2010–2015 and the UPPSAT (Uppsala-Athens) study (postpartum, n = 1565) in 2006–2007. Cases were defined according to presence of depressive symptoms during pregnancy (gestational week 32) and 6 weeks postpartum, using the Edinburgh Postnatal Depression Scale (EPDS). Exposure of sunshine, temperature, precipitation, snow coverage, and air pollen counts of durations of 1, 7, and 42 days prior to the outcome were studied for associations with depressive symptoms, using negative binomial regression.
Prior to Bonferroni correction, the concentration of mugwort pollen, both one week and six weeks before the EPDS assessment at gestational week 32, was inversely associated with depressive symptoms in pregnancy, both before and after adjustment for season. No associations were found between the exposure to meteorological parameters and pollen and depressive symptoms, at the same day of depressive symptoms’ assessment, the previous week, or the six weeks prior to assessment, either during pregnancy or postpartum after Bonferroni correction.
There was no evidence that neither short-term nor long-term exposure to meteorological parameters or air pollen counts were associated with self-reported peripartum depressive symptoms in Uppsala, Sweden.
Improvement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.
We aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission.
We obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants. Primary outcome was week 6 response; secondary outcomes were week 6 remission and week 12 response and remission. We compared models that only included improvement in total score by week 2 (total improvement model) with models that also included improvement in individual symptoms.
For week 6 response, the area under the receiver operating characteristic curve and negative and positive predictive values of the total improvement model were 0.73, 0.67 and 0.74 compared with 0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased for week 12 outcomes. Of predicted non-responders, 29% actually did respond by week 6 and 43% by week 12, which was decreased from the baseline (overall) probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with continuous rather than dichotomous early improvement, including individual items did not enhance model performance.
Examining individual symptoms adds little to the predictive ability of early improvement. Additionally, early non-improvement does not rule out response or remission, particularly after 12 rather than 6 weeks. Therefore, our findings suggest that routinely adapting pharmacological treatment because of limited early improvement would often be premature.