The aim of this paper is to review some of the models and solution techniques used in the simulation of high-power semiconductor lasers and to address open questions. We discuss some of the ...peculiarities in the description of the optical field of wide-aperture lasers. As an example, the role of the substrate as a competing waveguide in GaAs-based lasers is studied. The governing equations for the investigation of modal instabilities and filamentation effects are presented and the impact of the thermal-lensing effect on the spatiotemporal behavior of the optical field is demonstrated. We reveal the factors that limit the output power at very high injection currents based on a numerical solution of the thermodynamic based drift-diffusion equations and elucidate the role of longitudinal spatial hole burning.
Summary
The fragile X mental retardation 1 gene (Fmr1) is polymorphic for CGG trinucleotide repeat number in the 5′‐untranslated region, with repeat lengths <45 associated with typical development ...and repeat lengths >200 resulting in hypermethylation and transcriptional silencing of the gene and mental retardation in the fragile X Syndrome (FXS). Individuals with CGG repeat expansions between 55 and 200 are carriers of the fragile X premutation (PM). PM carriers show a phenotype that can include anxiety, depression, social phobia, and memory deficits. They are also at risk for developing fragile X–associated tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by tremor, ataxia, cognitive impairment, and neuropathologic features including intranuclear inclusions in neurons and astrocytes, loss of Purkinje cells, and white matter disease. However, very little is known about dendritic morphology in PM or in FXTAS. Therefore, we carried out a Golgi study of dendritic complexity and dendritic spine morphology in layer II/III pyramidal neurons in primary visual cortex in a knock‐in (KI) mouse model of the PM. These CGG KI mice carry an expanded CGG trinucleotide repeat on Fmr1, and model many features of the PM and FXTAS. Compared to wild‐type (WT) mice, CGG KI mice showed fewer dendritic branches proximal to the soma, reduced total dendritic length, and a higher frequency of longer dendritic spines. The distribution of morphologic spine types (e.g., stubby, mushroom, filopodial) did not differ between WT and KI mice. These findings demonstrate that synaptic circuitry is abnormal in visual cortex of mice used to model the PM, and suggest that such changes may underlie neurologic features found in individuals carrying the PM as well as in individuals with FXTAS.
The Kv2.1 delayed rectifier potassium channel exhibits high‐level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in ...hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity‐dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1−/−) mice lacking this channel. Kv2.1−/− mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1−/− mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1−/− mice appear unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1−/− animals. Field recordings from hippocampal slices of Kv2.1−/− mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1−/− mice, long‐term potentiation at the Schaffer collateral – CA1 synapse is decreased. Kv2.1−/− mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1−/− mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1−/− mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function.
Kv2.1 mutant mice are strikingly hyperactive, susceptible to convulsant‐induced seizures and defective in learning.
The fabrication and characterisation details of novel distributed Bragg reflector (DBR) diode lasers emitting around 1064 nm are presented here. The AlGaAs epitaxial layer stack used here allows the ...removal of the active quantum wells in passive sections where no current is injected. The DBR lasers fabricated with a two‐step epitaxial approach without an active layer in the grating sections show improved performance in terms of power, efficiency, and linewidth in comparison to its all‐active DBR counterparts.
Summary
Cortical dysplasia of various types, reflecting abnormalities of brain development, have been closely associated with epileptic activities. Yet, there remains considerable discussion about ...if/how these structural lesions give rise to seizure phenomenology. Animal models have been used to investigate the cause–effect relationships between aberrant cortical structure and epilepsy. In this article, we discuss three such models: (1) the Eker rat model of tuberous sclerosis, in which a gene mutation gives rise to cortical disorganization and cytologically abnormal cellular elements; (2) the p35 knockout mouse, in which the genetic dysfunction gives rise to compromised cortical organization and lamination, but in which the cellular elements appear normal; and (3) the methylazoxymethanol‐exposed rat, in which time‐specific chemical DNA disruption leads to abnormal patterns of cell formation and migration, resulting in heterotopic neuronal clusters. Integrating data from studies of these animal models with related clinical observations, we propose that the neuropathologic features of these cortical dysplastic lesions are insufficient to determine the seizure‐initiating process. Rather, it is their interaction with a more subtly disrupted cortical “surround” that constitutes the circuitry underlying epileptiform activities as well as seizure propensity and ictogenesis.
Summary
Purpose: Periventricular nodular heterotopia (PNH) is, in humans, often associated with difficult‐to‐control epilepsy. However, there is considerable controversy about the role of the PNH in ...seizure generation and spread. To study this issue, we have used a rat model in which injection of methylazoxymethanol (MAM) into pregnant rat dams produces offspring with nodular heterotopia‐like brain abnormalities.
Methods: Electrophysiologic methods were used to examine the activity of the MAM‐induced PNH relative to activity in the neighboring hippocampus and overlying neocortex. Recordings were obtained simultaneously from these three structures in slice preparations from MAM‐exposed rats and in intact animals. Bath application or systemic injection of bicuculline was used to induce epileptiform activity.
Key Findings: In the in vitro slice, epileptiform discharge was generally initiated in hippocampus. In some cases, independent PNH discharge occurred, but the PNH never “led” discharges in hippocampus or neocortex. Intracellular recordings from PNH neurons confirmed that these cells received synaptic drive from both hippocampus and neocortex, and sent axonal projections to these structures—consistent with anatomic observations of biocytin‐injected PNH cells. In intact animal preparations, bicuculline injection resulted in epileptiform discharge in all experiments, with a period of ictal‐like electrographic activity typically initiated within 2–3 min after drug injection. In almost all animals, the onset of ictus was seen synchronously across PNH, hippocampal, and neocortical electrodes; in a few cases, the PNH electrode (histologically confirmed) did not participate, but in no case was activity initiated in the PNH electrode. Interictal discharge was also synchronized across all three electrodes; again, the PNH never “led” the other two electrodes, and typically followed (onset several milliseconds after hippocampal/neocortical discharge onset).
Significance: These results do not support the hypothesis that the PNH lesion is the primary epileptogenic site, since it does not initiate or lead epileptiform activity that subsequently propagates to other brain regions.
A review of existing life cycle assessments (LCAs) on paper and cardboard waste has been undertaken. The objectives of the review were threefold. Firstly, to see whether a consistent message comes ...out of published LCA literature on optimum disposal or recycling solutions for this waste type. Such message has implications for current policy formulation on material recycling and disposal in the EU. Secondly, to identify key methodological issues of paper waste management LCAs, and enlighten the influence of such issues on the conclusions of the LCA studies. Thirdly, in light of the analysis made, to discuss whether it is at all valid to use the LCA methodology in its current development state to guide policy decisions on paper waste.
A total of nine LCA studies containing altogether 73 scenarios were selected from a thorough, international literature search. The selected studies are LCAs including comparisons of different management options for waste paper.
Despite claims of inconsistency, the LCAs reviewed illustrate the environmental benefits in recycling over incineration or landfill options, for paper and cardboard waste. This broad consensus was found despite differences in geographic location and definitions of the paper recycling/disposal systems studied. A systematic exploration of the LCA studies showed, however, important methodological pitfalls and sources of error, mainly concerning differences in the definition of the system boundaries. Fifteen key assumptions were identified that cover the three paper cycle system areas: raw materials and forestry, paper production, and disposal/recovery. It was found that the outcome of the individual LCA studies largely depended on the choices made in some of these assumptions, most specifically the ones concerning energy use and generation, and forestry.
Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caused by CGG trinucleotide repeat expansions in the fragile X mental retardation 1 ( FMR1 ) ...gene. The neuropathological hallmark of the disease is the presence of ubiquitin-positive intranuclear inclusions in neurons and in astrocytes. Ubiquitin-positive intranuclear inclusions have also been found in the neurons of transgenic mice model carrying an expanded CGG(98) trinucleotide repeat of human origin but have not previously been described in glial cells. Therefore, we used immunocytochemical methods to determine the pathological features of nuclear and/or cytoplasmic inclusions in astrocytes, Bergmann glia, and neurons, as well as relationships between inclusion patterns, age, and repeat length in CGG knock-in (KI) mice in comparison with wild-type mice. In CGG KI mice, ubiquitin-positive intranuclear inclusions were found in neurons (e.g., pyramidal cells, GABAergic neurons) throughout the brain in cortical and subcortical brain regions; these inclusions increased in number and size with advanced age. Ubiquitin-positive intranuclear inclusions were also present in protoplasmic astrocytes, including Bergmann glia in the cerebellum. The morphology of intranuclear inclusions in CGG KI mice was compared to that of typical inclusions in human neurons and astrocytes in postmortem FXTAS brain tissue. This new finding of previously unreported pathology in astrocytes of CGG KI mice now provides an important mouse model to study astrocyte pathology in human FXTAS.
Recently, the safety of laparoscopic radical hysterectomy (LRH) has been called into question in early-stage cervical cancer. This study aimed to evaluate overall survival (OS) and disease-free ...survival (DFS) in patients treated with abdominal radical hysterectomy (ARH) and LRH for early-stage cervical cancer and to provide a literature review.
Patients diagnosed between 2010 and 2017 with International Federation of Gynaecology and Obstetrics (2009) stage IA2 with lymphovascular space invasion, IB1 and IIA1, were identified from the Netherlands Cancer Registry. Cox regression with propensity score, based on inverse probability treatment weighting, was applied to examine the effect of surgical approach on 5-year survival and calculate hazard ratios (HR) and 95% confidence intervals (CIs). Literature review included observational studies with (i) analysis on tumours ≤4 cm (ii) median follow-up ≥30 months (iii) ≥5 events per predictor parameter in multivariable analysis or a propensity score.
Of the 1109 patients, LRH was performed in 33%. Higher mortality (9.4% vs. 4.6%) and recurrence (13.1% vs. 7.3%) were observed in ARH than LRH. However, adjusted analyses showed similar DFS (89.4% vs. 90.2%), HR 0.92 95% CI: 0.52–1.60) and OS (95.2% vs. 95.5%), HR 0.94 95% CI: 0.43–2.04). Analyses on tumour size (<2/≥2 cm) also gave similar survival rates. Review of nine studies showed no distinct advantage of ARH, especially in tumours <2 cm.
After adjustment, our retrospective study showed equal oncological outcomes between ARH and LRH for early-stage cervical cancer – also in tumours <2 cm. This is in correspondence with results from our literature review.
•Oncological outcome is equal after abdominal and laparoscopic radical hysterectomy.•Disease-free survival and overall survival are equal in tumours <2 cm.•The exact role of laparoscopy should be examined in prospective randomised trials.
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