The prognostic value of the presence of pelvic and/or para-aortic lymph node metastases in cervical cancer patients; the influence of the new FIGO classification (stage IIIC).

INTRODUCTION: One of the major changes in the revised (2018) FIGO-staging system is the addition of stage IIIC to the previously used 2009 system. We evaluated the prognostic value of positive pelvic and/or para-aortic lymph nodes in patients with cervical cancer. METHODS: A nationwide retrospective cohort study was performed by analyzing data from the Netherlands Cancer Registry. All patients newly diagnosed with stage IB-IVA between 2005 and 2018 were identified. Three-year, 5-year and 15-year overall survival (OS) rates were estimated with the Kaplan-Meier method. RESULTS: Of the included 6082 patients, 1740 patients (29%) had pelvic and/or para-aortic lymph node metastases. For patients with FIGO 2009 stage IB-IB1-IIA-IIA1 and stage IB2-IIA2-IIB with pelvic and/or para-aortic lymph node metastases the OS was significantly different (p < 0.001 and p = 0.009), with a 5-year OS of 77% and 67%, compared with 92% and 74% for women without lymph node metastases. For FIGO 2009 stage IIIA-IIIB-IVA with and without lymph node metastases, survival rates are not significantly different (p = 0.064). For FIGO 2018 stage IIIC the 3y-OS, 5y-OS and 15-year OS are 72%, 65% and 59% respectively. Survival rates of IIIC diagnosed based on imaging (IIICr) are significantly impaired compared to stage IIIC diagnosed based on pathology (IIICp) (p < 0.001). CONCLUSION: Patients with FIGO 2009 stage IB-IIB cervical cancer with pelvic and/or para-aortic lymph node metastases have significantly impaired survival compared to patients without metastases. Survival rates of patients with FIGO 2009 stage IIIA-IVA are not affected by lymph node metastases.

Antimicrobial resistance of Helicobacter pylori in Germany, 2015 to 2018.

OBJECTIVES: National and international guidelines recommend empiric first-line treatments of individuals infected with Helicobacter pylori without prior antimicrobial susceptibility testing. For this reason, knowledge of primary resistance to first-line antibiotics such as clarithromycin is essential. We assessed the primary resistance of H. pylori in Germany to key antibiotics by molecular genetic methods and evaluated risk factors for the development of resistance. METHODS: Gastric tissue samples of 1851 yet treatment-naïve H. pylori-positive patients were examined with real-time PCR or PCR and Sanger sequencing for mutations conferring resistance to clarithromycin, levofloxacin and tetracycline. Clinical and epidemiological data were documented and univariable and multivariable logistic regression analyses were conducted. RESULTS: Overall primary resistances were 11.3% (210/1851) to clarithromycin, and 13.4% (201/1497) to levofloxacin; resistance to tetracycline (2.5%, 38/1497) was as low as combined resistance to clarithromycin/levofloxacin (2.6%, 39/1497). Female sex and prior antimicrobial therapies owing to unrelated bacterial infections were risk factors for clarithromycin resistance (adjusted OR (aOR) 2.3, 95% CI 1.6-3.4; and 2.6, 95% CI 1.5-4.5, respectively); older age was associated with levofloxacin resistance (aOR for those ≥65 years compared with those 18-35 years: 6.6, 95% CI 3.1-14.2). CONCLUSIONS: Clarithromycin might still be recommended in first-line eradication therapies in yet untreated patients, but as nearly every tenth patient may carry clarithromycin-resistant H. pylori it may be advisable to rule out resistance ahead of treatment by carrying out susceptibility testing or prescribing an alternative therapy.

Astroglial-targeted expression of the fragile X CGG repeat premutation in mice yields RAN translation, motor deficits and possible evidence for cell-to-cell propagation of FXTAS pathology.

The fragile X premutation is a CGG trinucleotide repeat expansion between 55 and 200 repeats in the 5'-untranslated region of the fragile X mental retardation 1 (FMR1) gene. Human carriers of the premutation allele are at risk of developing the late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Characteristic neuropathology associated with FXTAS includes intranuclear inclusions in neurons and astroglia. Previous studies recapitulated these histopathological features in neurons in a knock-in mouse model, but without significant astroglial pathology. To determine the role of astroglia in FXTAS, we generated a transgenic mouse line (Gfa2-CGG99-eGFP) that selectively expresses a 99-CGG repeat expansion linked to an enhanced green fluorescent protein (eGFP) reporter in astroglia throughout the brain, including cerebellar Bergmann glia. Behaviorally these mice displayed impaired motor performance on the ladder-rung test, but paradoxically better performance on the rotarod. Immunocytochemical analysis revealed that CGG99-eGFP co-localized with GFAP and S-100ß, but not with NeuN, Iba1, or MBP, indicating that CGG99-eGFP expression is specific to astroglia. Ubiquitin-positive intranuclear inclusions were found in eGFP-expressing glia throughout the brain. In addition, intracytoplasmic ubiquitin-positive inclusions were found outside the nucleus in distal astrocyte processes. Intriguingly, intranuclear inclusions, in the absence of eGFP mRNA and eGFP fluorescence, were present in neurons of the hypothalamus and neocortex. Furthermore, intranuclear inclusions in both neurons and astrocytes displayed immunofluorescent labeling for the polyglycine peptide FMRpolyG, implicating FMRpolyG in the pathology found in Gfa2-CGG99 mice. Considered together, these results show that Gfa2-CGG99 expression in mice is sufficient to induce key features of FXTAS pathology, including formation of intranuclear inclusions, translation of FMRpolyG, and deficits in motor function.

High-power sampled-grating-based master oscillator power amplifier system with 23.5 nm wavelength tuning around 970 nm.

Tunable high-power diode lasers are key components in various established and emerging applications. In this work, we present a compact hybrid master oscillator power amplifier (MOPA) laser system. The system utilizes a tunable GaAs-based sampled-grating (SG) distributed Bragg reflector (DBR) laser as the master oscillator (MO), which emits around a wavelength of 970 nm in a single longitudinal mode with a spectral width below 20 pm. The SG-DBR laser consists of two SGs, each of which can be thermally tuned with microheaters. By tuning one of the two SGs, a discrete wavelength tuning of 21.1 nm can be obtained with a Vernier mode spacing of about 2.3 nm. By tuning both SGs, 23.5 nm of quasi-continuous tuning is obtained, with a mode spacing of about 115 pm. The coupling of the beam emitted by the MO into a tapered power amplifier provides an amplified output power in the watt range having a nearly diffraction-limited beam with a propagation factor of M1/e22=1.6. The combination of high power and wide wavelength tuning in a compact system makes this light source ideal for, among other things, nonlinear frequency conversion.

Psychological risk factors in back pain patients at an orthopaedic outpatient clinic.

BACKGROUND: Psychological risk factors have shown to be important prognostic indicators of back surgery outcome. Prevalence of these risk factors has rarely been examined in an outpatient clinic population. Furthermore, it is unclear to which extent they play a role, in absence of routinely used psychological screening tools, in treatment assignment. OBJECTIVE: First aim of this study was to examine the prevalence of psychological risk factors in back pain patients at an orthopaedic outpatient clinic. Second aim was to investigate the prognostic value of these identified risk factors in treatment assignment by the orthopaedic surgeons (conservative vs. surgery). METHODS: Sixty-six adult back pain patients were included. Psychological risk factor prevalence was determined with the Hospital Anxiety and Depression Scale, Tampa Scale of Kinesiophobia and Pain Catastrophizing Scale. Prognostic value of these risk factors in treatment assignment was examined using statistics. RESULTS: Respectively, 30 (45% HADS Anxiety), 27 (41%, HADS Depression), 19 (29%, PCS) and 37 (56%, TSK) patients scored above cut-off. No prognostic value of risk factors in treatment assignment, was found. CONCLUSIONS: The majority of patients in our study is at risk of poor surgical outcome due to presence of psychological risk factors. Future studies should target the development of screening tools for an early identification of those at risk.

[How Reliable are Meta-Analyses? An Appraisal Using the Example of Magnesium Tocolysis]. / Wie verlässlich sind Metaanalysen? Eine Überprüfung am Beispiel der Magnesiumtokolyse.

INTRODUCTION: Crowther et al. 3 analysed the effectivity of magnesium tocolysis in preventing preterm birth. They conclude that there is no evidence for protection. In its latest guidelines, based on this Cochrane analysis, the German Association of Gynaecology and Obstetrics (DGGG) does not recommend any more the use of magnesium for tocolysis. Magnesium tocolysis is said neither to delay nor to prevent preterm birth. Moreover, magnesium could be responsible for increased mortality in infants. These conclusions are mostly based on the research of Mittendorf et al. 4. In a Cochrane study from 2014, which in principal was identical to the study mentioned above 3, Crowther et al. 6 confirm the previous findings and conclusions. METHOD: Having successfully applied magnesium tocolysis for many years, these surprising conclusions led us to review the soundness of the publications mentioned above. Combining the practical experience of many years with the results of a comprehensive literature retrieval, we finally contrasted this knowledge with the findings of the aforementioned publications that caused the DGGG to withdraw the recommendation for magnesium. RESULTS: To draw binding consequences from a meta-analysis is possible only when stringent quality guidelines are observed. The studies that were included in the Cochrane review of Crowther et al. 3 are very heterogeneous and are not suitable for concluding on poor or even lacking effectiveness of magnesium tocolysis. Furthermore, the cases of infant deaths, as stated by Mittendorf et al. 4, are very unlikely caused by magnesium. CONCLUSION: When including studies in a meta-analysis special attention has to be given to the relevance and unbiased selection of studies. To prevent any misjudgment, a thorough knowledge of the included studies seems essentiell. There is not sufficient evidence to withdraw the recommendation for applying magnesium tocolysis as a preventive measure to prevent preterm birth. In the sense of evidence-based medicine, long-standing, scientifically proven therapeutic success should be incorporated into the meta-analysis as well.

Nodule excitability in an animal model of periventricular nodular heterotopia: c-fos activation in organotypic hippocampal slices.

OBJECTIVE: Aberrations in brain development may lead to dysplastic structures such as periventricular nodules. Although these abnormal collections of neurons are often associated with difficult-to-control seizure activity, there is little consensus regarding the epileptogenicity of the nodules themselves. Because one common treatment option is surgical resection of suspected epileptic nodules, it is important to determine whether these structures in fact give rise, or essentially contribute, to epileptic activities. METHODS: To study the excitability of aberrant nodules, we have examined c-fos activation in organotypic hippocampal slice cultures generated from an animal model of periventricular nodular heterotopia created by treating pregnant rats with methylazoxymethanol acetate. Using this preparation, we have also attempted to assess tissue excitability when the nodule is surgically removed from the culture. We then compared c-fos activation in this in vitro preparation to c-fos activation generated in an intact rat treated with kainic acid. RESULTS: Quantitative analysis of c-fos activation failed to show enhanced nodule excitability compared to neocortex or CA1 hippocampus. However, when we compared cultures with and without a nodule, presence of a nodule did affect the excitability of CA1 and cortex, at least as reflected in c-fos labeling. Surgical removal of the nodule did not result in a consistent decrease in excitability as reflected in the c-fos biomarker. SIGNIFICANCE: Our results from the organotypic culture were generally consistent with our observations on excitability in the intact rat-as seen not only with c-fos but also in previous electrophysiologic studies. At least in this model, the nodule does not appear to be responsible for enhanced excitability (or, presumably, seizure initiation). Excitability is different in tissue that contains a nodule, suggesting altered network function, perhaps reflecting the abnormal developmental pattern that gave rise to the nodule.

Generation of spectrally stable continuous-wave emission and ns pulses with a peak power of 4 W using a distributed Bragg reflector laser and a ridge-waveguide power amplifier.

We have developed a diode-laser based master oscillator power amplifier (MOPA) light source which emits high-power spectrally stabilized and nearly-diffraction limited optical pulses in the nanoseconds range as required by many applications. The MOPA consists of a distributed Bragg reflector (DBR) laser as master oscillator driven by a constant current and a ridge waveguide power amplifier (PA) which can be driven by a constant current (DC) or by rectangular current pulses with a width of 5 ns at a repetition frequency of 200 kHz. Under pulsed operation the amplifier acts as an optical gate, converting the CW input beam emitted by the DBR laser into a train of short amplified optical pulses. With this experimental MOPA arrangement no relaxation oscillations occur. A continuous wave power of 1 W under DC injection and a pulse power of 4 W under pulsed operation are reached. For both operational modes the optical spectrum of the emission of the amplifier exhibits a peak at a constant wavelength of 973.5 nm with a spectral width < 10 pm.

Frequency doubling of a passively mode-locked monolithic distributed Bragg reflector diode laser.

In this work, frequency doubling of a passively mode-locked 3.5 mm long monolithic distributed Bragg reflector diode laser is investigated experimentally. At 1064 nm, optical pulses with a duration of 12.4 ps are generated at a repetition rate of 13 GHz and a peak power of 825 mW, resulting in an average power of 133 mW. Second-harmonic generation is carried out in a periodically poled MgO-doped LiNbO3 ridge waveguide at a normalized nonlinear conversion efficiency of 930%/W. A maximum average second-harmonic power of 40.9 mW, corresponding to a pulse energy of 3.15 pJ, is reached in the experiment at an opto-optical conversion efficiency of 30.8%. The normalized nonlinear conversion efficiency in mode-locked operation is more than 2 times larger compared to continuous-wave operation.

Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability.

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.

Future waste treatment and energy systems--examples of joint scenarios.

Development and use of scenarios for large interdisciplinary projects is a complicated task. This article provides practical examples of how it has been carried out in two projects addressing waste management and energy issues respectively. Based on experiences from the two projects, recommendations are made for an approach concerning development of scenarios in projects dealing with both waste management and energy issues. Recommendations are given to develop and use overall scenarios for the project and leave room for sub-scenarios in parts of the project. Combining different types of scenarios is recommended, too, in order to adapt to the methods and tools of different disciplines, such as developing predictive scenarios with general equilibrium tools and analysing explorative scenarios with energy system analysis tools. Furthermore, as marginals identified in differing future background systems determine the outcomes of consequential life cycle assessments (LCAs), it is considered advisable to develop and use explorative external scenarios based on possible marginals as a framework for consequential LCAs. This approach is illustrated using an on-going Danish research project.

Dynamics of a gain-switched distributed feedback ridge waveguide laser in nanoseconds time scale under very high current injection conditions.

We present detailed experimental investigations of the temporal, spectral and spatial behavior of a gain-switched distributed feedback (DFB) laser emitting at a wavelength of 1064 nm. Gain-switching is achieved by injecting nearly rectangular shaped current pulses having a length of 50 ns and a very high amplitude up to 2.5 A. The repetition frequency is 200 kHz. The laser has a ridge waveguide (RW) for lateral waveguiding with a ridge width of 3 µm and a cavity length of 1.5 mm. Time resolved investigations show, depending on the amplitude of the current pulses, that the optical power exhibits different types of oscillatory behavior during the pulses, accompanied by changes in the lateral near field intensity profiles and optical spectra. Three different types of instabilities can be distinguished: mode beating with frequencies between 25 GHz and 30 GHz, switching between different lateral intensity profiles with a frequency of 0.4 GHz and self-sustained oscillations with a frequency of 4 GHz. The investigations are of great relevance for the utilization of gain-switched DFB-RW lasers as seed lasers for fiber laser systems and in other applications, which require a high optical power.

Are developmental dysplastic lesions epileptogenic?

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.

Acute, but reversible, kainic acid-induced DNA damage in hippocampal CA1 pyramidal cells of p53-deficient mice.

p53 plays an essential role in mediating apoptotic responses to cellular stress, especially DNA damage. In a kainic acid (KA)-induced seizure model in mice, hippocampal CA1 pyramidal cells undergo delayed neuronal death at day 3-4 following systemic KA administration. We previously demonstrated that CA1 neurons in p53(-/-) animals are protected from such apoptotic neuronal loss. However, extensive morphological damage associated with DNA strand breaks in CA1 neurons was found in a fraction of p53(-/-) animals at earlier time points (8 h to 2 days). No comparable acute damage was observed in wild-type animals. Stereological counting confirmed that there was no significant loss of CA1 pyramidal cells in p53(-/-) animals at 7 days post-KA injection. These results suggest that seizure-induced DNA strand breaks are accumulated to a greater extent but do not lead to apoptosis in the absence of p53. In wild-type animals, therefore, p53 appears to stimulate DNA repair and also mediate apoptosis in CA1 neurons in this excitotoxicity model. These results also reflect remarkable plasticity of neurons in recovery from injury.

Abnormal dendrite and spine morphology in primary visual cortex in the CGG knock-in mouse model of the fragile X premutation.

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.

Inhibition and interneuron distribution in the dentate gyrus of p35 knockout mice.

The p35 knockout (p35-/-) mouse is an animal model of temporal lobe epilepsy that recapitulates key neuroanatomic abnormalities-granule cell dispersion and mossy fiber sprouting-observed in the hippocampal formation of humans, as well as spontaneous seizure activity. It is a useful model in which to study the relationship between the abnormal neuronal structure and seizure activity to further our understanding of cortical dysplasia in epileptogenesis. Our previous work using this mouse model characterized the anatomic features of the dentate granule cells and the functional implications of these abnormalities on increased recurrent excitation. These data also suggested that there might be compromised inhibition in this animal model. We pursued this possibility, focusing our investigation on inhibitory circuitry. In preliminary investigations using neuroanatomic tools (immunocytochemistry, camera lucida reconstructions of individually labeled interneurons, and electron microscopy) combined with intracellular electrophysiology, we observed no significant reduction in the number of symmetric versus asymmetric synaptic contacts on dentate granule cell somata, and no statistically significant changes in evoked early or late inhibition. Although there were some abnormalities in the morphology/distribution of inhibitory interneurons (as well as a larger population of dentate granule cells) of the dentate gyrus, overall inhibition in the p35 knockout mouse appeared to be largely intact.

Initiation of epileptiform activity in a rat model of periventricular nodular heterotopia.

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.

Diabetes inpatients: a case of lose, lose, lose. Is it time to use a 'diabetes-attributable hospitalization cost' to assess the impact of diabetes?

AIMS: The UK National Health Service in England pays for inpatients using a formula ('tariff'). The appropriateness of the tariff for people with diabetes is unknown. We have compared the tariff paid and costs for inpatients with/without diabetes and tested the concept of a 'diabetes-attributable hospitalization cost'. METHODS: This was a cross-sectional, retrospective 12-month audit in a single teaching hospital assessing mortality, bed days per annum and 'diabetes-attributable hospitalization cost' (i.e. the proportion of costs for all patients with diabetes in excess of that paid for comparable patients without diabetes). RESULTS: There were 64 829 inpatient admissions, with 4864 of those coded as having diabetes; 12.9% was estimated to be the number of patients having diabetes but not coded. People with diabetes occupied 13.9% of all bed days and were 18.1% (1.3-37.8%) more likely to die (age adjusted). The mean bed days per annum were greatest among those with (vs. without) diabetes (men 10.9 ± 17.0 vs. 6.3 ± 12.8; women 11.4 ± 19.4 vs. 5.9 ± 11.6; P < 0.001). The greatest excess admission rates were among those aged 25-64 years. The annual mean tariff was greater for those with diabetes (5380 ± 8740) than those without diabetes (3706 ± 6221) (P < 0.001). The overall cost was even higher among those with diabetes: 5835 ± 11 246 vs. 3567 ± 7238 (P < 0.001). The diabetes-attributable hospitalization cost was 46.5% (9 125 085). An HbA(1c) > 10.0% (> 86 mmol/mol) was associated with excess hospitalization. CONCLUSIONS: Those with diabetes cost more and are more likely to die when inpatients. The tariff paid for diabetes is high, but in this centre less than the actual costs. Approaches known to reduce hospitalization are urgently required.

Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury?

Traumatic brain injury (TBI) frequently leads to epilepsy. The process of epileptogenesis - the development of that seizure state - is still poorly understood, and effective antiepileptogenic treatments have yet to be identified. The ketogenic diet (KD) has been shown to be effective as an antiepileptic therapy, but has not been extensively tested for its efficacy in preventing the development of the seizure state, and certainly not within the context of TBI-induced epileptogenesis. We have used a rat model of TBI - fluid percussion injury (FPI) - to test the hypothesis that KD treatment is antiepileptogenic and protects the brain from neuronal cell loss following TBI. Rats fed a KD had a higher seizure threshold (longer latency to flurothyl-induced seizure activity) than rats fed a standard diet (SD); this effect was seen when KD was in place at the time of seizure testing (3 and 6 weeks following FPI), but was absent when KD had been replaced by SD at time of testing. FPI caused significant hippocampal cell loss in both KD-fed and SD-fed rats; the degree of cell loss appeared to be reduced by KD treatment before FPI but not after FPI. These results are consistent with prior demonstrations that KD raises seizure threshold, but do not provide support for the hypothesis that KD administered for a limited time directly before or after FPI alters later seizure sensitivity; that is, within the limits of this model and protocol, there is no evidence for KD-induced antiepileptogenesis.

High-power distributed Bragg reflector ridge-waveguide diode laser with very small spectral linewidth.

We manufactured and investigated distributed Bragg reflector ridge-waveguide diode lasers having sixth-order surface gratings and an emission wavelength around 974 nm. The single-mode output power of the lasers with a total length of 4 mm exceeded 1 W. A very small spectral linewidth of 1.4 MHz (3 dB) consisting of a Lorentzian part of 146 kHz and a Gaussian part of 1308 MHz was measured using a self-delayed heterodyne measurement technique.