Estimating cortical thickness trajectories in children across different scanners using transfer learning from normative models.

This work illustrates the use of normative models in a longitudinal neuroimaging study of children aged 6-17 years and demonstrates how such models can be used to make meaningful comparisons in longitudinal studies, even when individuals are scanned with different scanners across successive study waves. More specifically, we first estimated a large-scale reference normative model using Hierarchical Bayesian Regression from N = 42,993 individuals across the lifespan and from dozens of sites. We then transfer these models to a longitudinal developmental cohort (N = 6285) with three measurement waves acquired on two different scanners that were unseen during estimation of the reference models. We show that the use of normative models provides individual deviation scores that are independent of scanner effects and efficiently accommodate inter-site variations. Moreover, we provide empirical evidence to guide the optimization of sample size for the transfer of prior knowledge about the distribution of regional cortical thicknesses. We show that a transfer set containing as few as 25 samples per site can lead to good performance metrics on the test set. Finally, we demonstrate the clinical utility of this approach by showing that deviation scores obtained from the transferred normative models are able to detect and chart morphological heterogeneity in individuals born preterm.

The Boltzmann project.

The International Committee for Weights and Measures (CIPM), at its meeting in October 2017, followed the recommendation of the Consultative Committee for Units (CCU) on the redefinition of the kilogram, ampere, kelvin and mole. For the redefinition of the kelvin, the Boltzmann constant will be fixed with the numerical value 1.380 649 × 10-23 J K-1. The relative standard uncertainty to be transferred to the thermodynamic temperature value of the triple point of water will be 3.7 × 10-7, corresponding to an uncertainty in temperature of 0.10 mK, sufficiently low for all practical purposes. With the redefinition of the kelvin, the broad research activities of the temperature community on the determination of the Boltzmann constant have been very successfully completed. In the following, a review of the determinations of the Boltzmann constant k, important for the new definition of the kelvin and performed in the last decade, is given.

Coccidioidal antigen reactive CD4+ T-lymphocytes in the cerebrospinal fluid in coccidioides immitis meningitis.

CSF lymphocytes from patients with Coccidioides immitis meningitis exhibited a significant antigen-specific response to in vitro stimulation with C. immitis antigens. In some patients, lesser responses to control antigens (Candida and PPD) were also detected. Antigen-specific responses by CSF lymphocytes were seen early in the course of this disease as well as several years after patients had entered remission. When compared to CSF cells, the response of autologous peripheral blood mononuclear cells was similar but of a much smaller magnitude and at times undetectable. Fluorescence activated cell sorting revealed an increased percentage of CD3+ (T-cells), CD4+ (helper/inducer) and CD3+/HLA-DR+ (activated T-cell) cells in the CSF of C. immitis meningitis patients compared to their blood. Most of the antigen-specific proliferative response resided in the CD4+ lymphocyte subset. CSF T-cell proliferation assays may have a role in the diagnosis of C. immitis meningitis.

Fluorescence in situ hybridization with a chromosome 21-specific cosmid contig: 1-day detection of trisomy 21 in uncultured mesenchymal chorionic villus cells.

We present a modified, fast trisomy 21 detection assay using fluorescence in situ hybridization (FISH) on uncultured mesenchymal chorionic villus cells. The whole test takes about 24 h. We used a cosmid contig as a probe and modified an in situ sample preparation method first described by Klinger et al. (1992). The assays saves time and cost of culture in comparison with a previously described trisomy 21 detection FISH assay (Bryndorf et al., 1993). A small blind clinical study comparing the modified and the previously described FISH assays using mesenchymal chorionic villus cells showed comparable results and concordance with conventional cytogenetic analysis. The frequency of nuclei with three hybridization signals from samples disomic for chromosome 21 ranged from 0 to 8 per cent with both assays, while trisomic samples had 60-80 and 54-90 per cent of the mesenchymal nuclei with three signals in the modified and previously described assays, respectively. Normal (disomic) and trisomic mesenchymal chorionic villus samples can be distinguished clearly and rapidly without culture in the modified assay.

New rapid test for prenatal detection of trisomy 21 (Down's syndrome): preliminary report.

OBJECTIVE: To devise and evaluate a rapid screening method for detecting trisomy 21 (Down's syndrome) in samples of uncultured amniotic fluid cells. DESIGN: Non-radioactive in situ hybridisation with HY128, a 500,000 base pair yeast artificial chromosome probe specific for chromosome 21. Blinded study of 12 karyotypically normal amniotic fluid samples and eight samples trisomic for chromosome 21. SETTING: Cytogenetic and obstetric services at a tertiary referral centre, Copenhagen. MAIN OUTCOME MEASURES: Time necessary to complete the test. Proportion of cell nuclei containing two and three hybridisation signals in karyotypically normal and abnormal amniotic fluid samples. RESULTS: The test could be completed within three to four days after amniocentesis. In the normal samples a mean of 73% (range 61-82%) of the amniotic cell nuclei showed two hybridisation signals and 6% (0-18%) showed three signals. By contrast, among the trisomic samples 29% (19-38%) of the nuclei exhibited two signals and 48% (31-60%) showed three signals. CONCLUSION: The technique clearly distinguished between normal and trisomic samples. Prenatal diagnosis with in situ hybridisation with chromosome specific probes was fast and may make it possible to screen for selected, aneuploidies. However, the technique is still at a preliminary stage and needs further evaluation and refinement.

Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment.

Identification of genes determining narcolepsy susceptibility is important not only for understanding that disorder but also for possible clues to general sleep-control mechanisms. Studies in humans reveal at least one such gene related to the major histocompatibility complex and in dog an as-yet-unmapped single, autosomal recessive gene canarc-1. Gene markers for canarc-1 were therefore sought by DNA restriction fragment length polymorphisms in our colony of narcoleptic dogs. A human mu-switch immunoglobulin probe and the enzyme Hae III identified a gene cosegregating with canarc-1 in backcrossed animals (logarithm of odds scores: m = 24, Z max = 7.2 at theta = 0%). canarc-1 was also shown not to be tightly linked with the dog major histocompatibility complex (m = 40, Z less than -2 at theta less than 4.8%). These results represent the mapping of a non-major histocompatibility complex narcolepsy gene and strongly suggest involvement of the immune system in the pathophysiology of that disease.

Polymorphic markers of human T-cell receptor alpha and beta genes. Family studies and comparison of frequencies in healthy individuals and patients with multiple sclerosis and myasthenia gravis.

Polymorphic markers for the human T-cell receptor (TcR) genes are described. With a TcR beta-chain probe, polymorphic allelic fragments of 5.4 and 1.8 kb were detected in KpnI digests, and fragments of 12.5 and 11.5 kb were seen in the BglII digests. Polymorphism in alpha chain genes was observed in TaqI-digested DNA samples with bands at 10.2 and 6.2-2.1 kb. Mendelian codominant inheritance for all three polymorphisms was confirmed in family studies. The gene frequencies for these alleles were determined in a sample of 70 normal unrelated Caucasian individuals, and were shown to be in Hardy-Weinberg equilibrium. There were no significant differences in the frequency of these polymorphic alpha and beta alleles between patients with multiple sclerosis and patients with myasthenia gravis as compared to a panel of control healthy individuals.

Susceptibility to multiple sclerosis associated with an immunoglobulin gamma 3 restriction fragment length polymorphism.

Susceptibility to multiple sclerosis (MS) has been linked to the immunoglobulin G (Gm) markers as well as HLA-DR genes. We have used a genomic Ig gamma 1 probe which detects polymorphisms in the gamma 1, gamma 2, gamma 3 and pseudogamma genes to identify restriction fragment length polymorphisms associated with MS. A negative association was found between a 5.9-kilobase (kb) Bst EII gamma 3 fragment and MS. Southern blot analysis of genomic DNA revealed the presence of this fragment in 84 of 140 (60.0%) controls, but in only 17 of 59 (28.8%) MS patients. The frequency of the fragment in 47 myasthenia gravis and 16 Graves' disease patients was similar to that in controls, 60.0 and 62.5%, respectively.

Supporting lactation when mothers and infants are separated: a clinical guideline for perinatal nurses.

It has been our intention to describe the vital role a nurse may play in assisting a woman to establish lactation successfully. Stitt indicates that the two most common reasons why women decline to breast-feed are (1) embarassment about their lack of knowledge of techniques and (2) fear of failure. Nurses are in a unique position to intervene constructively in both instances. It is essential for nurses to explore their own feelings about breast-feeding and sexuality and to help each other recognize how attitudes and values affect care. Only through understanding ourselves can we become sensitive to the desires of those who need our care.