Trait-like characteristics of the sleep EEG across adolescent development

Waking and sleep data in adults show high heritability and trait-like characteristics in EEG spectra. This phenomenon has not been examined in children and adolescents where brain development influences the EEG. The present study examines whether a trait-like sleep EEG pattern is detectable across adolescent development. Two consecutive nights of standard sleep recordings were performed in 19 9-10-year-old children and 26 15-16-year-old teens, and were repeated 1.5-3 years later. EEG spectra averaged across the night for non-rapid eye movement and rapid eye movement sleep separately were classified using hierarchical cluster analysis, which showed that all 4 nights of a participant clustered together for a majority of participants. Intraclass correlation coefficients were also very high (>0.7) across nights separated by several years, indicating a trait-like feature of the sleep EEG. In summary, our results, using two measures of stability, indicate that a "trait-like" aspect can be detected in the sleep EEG across adolescent development despite considerable neurodevelopmental changes. This finding indicates that the brain oscillators responsible for generating the sleep EEG signal remain relatively stable across adolescent development

Clinical case seminar - Hypogonadotropic hypogonadism as a presenting feature of late-onset X-linked adrenal hypoplasia congenita

Mutations in the orphan nuclear receptor DAX-1 cause X-linked adrenal hypoplasia congenita. Affected boys usually present with primary adrenal failure in early infancy or childhood. Impaired sexual development because of hypogonadotropic hypogonadism becomes apparent at the time of puberty. We report adult-onset adrenal hypoplasia congenita in a patient who presented with hypogonadism at 28 yr of age. Although he had no clinical evidence of adrenal dysfunction, compensated primary adrenal failure was diagnosed by biochemical testing. Semen analysis showed azoospermia, and he did not achieve fertility after 8 months of treatment with gonadotropins. A novel Y380D DAX-1 missense mutation, which causes partial loss of function in transient gene expression assays, was found in this patient. This case demonstrates that partial loss-of-function mutations in DAX1 can present with hypogonadotropic hypogonadism and covert adrenal failure in adulthood. Further, an important role for DAX-1 in spermatogenesis in humans is confirmed, supporting findings in the Dax1 (Ahch) knockout mouse

Multiexcitons confined within a sub-excitonic volume: Spectroscopic and dynamical signatures of neutral and charged biexcitons in ultrasmall semiconductor nanocrystals

The use of ultrafast gating techniques allows us to resolve both spectrally and temporally the emission from short-lived neutral and negatively charged biexcitons in ultrasmall (sub-10 nm) CdSe nanocrystals (nanocrystal quantum dots). Because of forced overlap of electronic wave functions and reduced dielectric screening, these states are characterized by giant interaction energies of tens (neutral biexcitons) to hundreds (charged biexcitons) of meV. Both types of biexcitons show extremely short lifetimes (from sub-100 picoseconds to sub-picosecond time scales) that rapidly shorten with decreasing nanocrystal size. These ultrafast relaxation dynamics are explained in terms of highly efficient nonradiative Auger recombination.Comment: 5 pages, 4 figures, to be published in Phys. Rev.

Factors associated with rifampin resistance in staphylococcal periprosthetic joint infections (PJI): a matched case-control study

Purpose: Rifampin combination therapy plays an important role in the management of staphylococcal periprosthetic joint infection (PJI). However, the emergence of rifampin resistance is a feared complication. We retrospectively analysed predetermined potential risk factors in patients with rifampin-resistant staphylococcal PJI in a multicentre case-control study. Methods: Cases (n=48) were defined as PJI caused by rifampin-resistant staphylococci. Rifampin-susceptible controls (n=48) were matched for microorganism and type of prosthetic joint. Uni- and multivariable conditional logistic regression analyses were performed to estimate odds ratios (OR) with 95% confidence intervals (95% CI). Results: Forty-eight cases (31 men; median age 67years; age range 39-88years) with hip- (n=29), knee- (n=13), elbow- (n=4), shoulder- (n=1) or ankle-PJI (n=1) were enrolled in the study. Staphylococcus aureus and coagulase-negative staphylococci were isolated in ten and 38 episodes, respectively. Most of the cases (n=44, 92%) had a previous PJI, and 93 % (n=41) of these had been treated with rifampin. There was an independent association of emergence of rifampin resistance with male sex (OR 3.6, 95% CI 1.2-11),≥3 previous surgical revisions (OR 4.7, 95% CI 1.6-14.2), PJI treatment with high initial bacterial load (inadequate surgical debridement, <2weeks of intravenous treatment of the combination medication; OR 4.9, 95% CI 1.6-15) and inadequate rifampin therapy (OR 5.4, 95% CI 1.2-25). Conclusions: Based on our results, extensive surgical debridement and adequate antibiotic therapy are needed to prevent the emergence of rifampin resistanc

Prolonged Outbreak of Mycobacterium chimaera Infection After Open-Chest Heart Surgery

A thorough epidemiological and microbiological investigation of this prolonged outbreak involving 6 open-chest heart surgery patients provided evidence for the airborne transmission of Mycobacterium chimaera, a slow-growing nontuberculous mycobacteria, from contaminated heater-cooler unit water tank

Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency

Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases. Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified. Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection. Setting: The study was conducted at secondary and tertiary referral centers. Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study. Interventions: There were no interventions. Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families. Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD

Spatio-temporal dynamics of quantum-well excitons

We investigate the lateral transport of excitons in ZnSe quantum wells by using time-resolved micro-photoluminescence enhanced by the introduction of a solid immersion lens. The spatial and temporal resolutions are 200 nm and 5 ps, respectively. Strong deviation from classical diffusion is observed up to 400 ps. This feature is attributed to the hot-exciton effects, consistent with previous experiments under cw excitation. The coupled transport-relaxation process of hot excitons is modelled by Monte Carlo simulation. We prove that two basic assumptions typically accepted in photoluminescence investigations on excitonic transport, namely (i) the classical diffusion model as well as (ii) the equivalence between the temporal and spatial evolution of the exciton population and of the measured photoluminescence, are not valid for low-temperature experiments.Comment: 8 pages, 6 figure

Photothermal Absorption Spectroscopy of Individual Semiconductor Nanocrystals

Photothermal heterodyne detection is used to record the first room-temperature absorption spectra of single CdSe/ZnS semiconductor nanocrystals. These spectra are recorded in the high cw excitation regime, and the observed bands are assigned to transitions involving biexciton and trion states. Comparison with the single nanocrystals photoluminescence spectra leads to the measurement of spectral Stokes shifts free from ensemble averaging