Enhancement of the Nonresonant Streaming Instability by Particle Collisions.

Streaming cosmic rays can power the exponential growth of a seed magnetic field by exciting a nonresonant instability that feeds on their bulk kinetic energy. By generating the necessary turbulent magnetic field, it is thought to play a key role in the confinement and acceleration of cosmic rays at shocks. In this Letter we present hybrid-particle-in-cell simulations of the nonresonant mode including Monte Carlo collisions, and investigate the interplay between the pressure anisotropies produced by the instability and particle collisions in the background plasma. Simulations of poorly ionized plasmas confirm the rapid damping of the instability by proton-neutral collisions predicted by linear fluid theory calculations. In contrast we find that Coulomb collisions in fully ionized plasmas do not oppose the growth of the magnetic field, but under certain conditions suppress the pressure anisotropies and actually enhance the magnetic field amplification.

Effect of soil temperature on optical frequency transfer through unidirectional dense-wavelength-division-multiplexing fiber-optic links.

Results of optical frequency transfer over a carrier-grade dense-wavelength-division-multiplexing (DWDM) optical fiber network are presented. The relation between soil temperature changes on a buried optical fiber and frequency changes of an optical carrier through the fiber is modeled. Soil temperatures, measured at various depths by the Royal Netherlands Meteorology Institute (KNMI) are compared with observed frequency variations through this model. A comparison of a nine-day record of optical frequency measurements through the 2×298 km fiber link with soil temperature data shows qualitative agreement. A soil temperature model is used to predict the link stability over longer periods (days-months-years). We show that optical frequency dissemination is sufficiently stable to distribute and compare, e.g., rubidium frequency standards over standard DWDM optical fiber networks using unidirectional fibers.

Retinal layer location of increased retinal thickness in eyes with subclinical and clinical macular edema in diabetes type 2.

PURPOSE: To identify the retinal layer predominantly affected in eyes with subclinical and clinical macular edema in diabetes type 2. METHODS: A cohort of 194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20/35) were examined with Cirrus spectral-domain optical coherence tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers of the eyes with subclinical and clinical macular edema was compared with a sample of 31 eyes from diabetic patients with normal OCT and an age-matched control group of 58 healthy eyes. RESULTS: From the 194 eyes in the study, 62 had subclinical macular edema and 12 had clinical macular edema. The highest increases in retinal thickness (RT) were found in the inner nuclear layer (INL; 33.6% in subclinical macular edema and 81.8% in clinical macular edema). Increases were also found in the neighboring layers. Thinning of the retina was registered in the retinal nerve fiber, ganglion cells and inner plexiform layers in the diabetic eyes without macular edema. CONCLUSIONS: The increase in RT occurring in diabetic eyes with macular edema is predominantly located in the INL but extends to neighboring retinal layers indicating that it may be due to extracellular fluid accumulation.

p38 inhibition and not MK2 inhibition enhances the secretion of chemokines from TNF-α activated rheumatoid arthritis fibroblast-like synoviocytes.

OBJECTIVES: For many years the p38 MAP kinase (MAPK) has been a major anti-inflammatory target for the development of an oral therapy for rheumatoid arthritis (RA). However, disappointing results from Phase II clinical studies suggest that adaptations may occur, which allow escape from blockade of the p38 pathway. In this study we investigated whether p38 inhibition mediated JNK activation represents such an escape mechanism. METHODS: Interaction between the JNK and p38 pathways was studied in TNF-α stimulated THP-1 monocytes, primary macrophages and fibroblast-like synoviocytes from OA and RA patients using pharmacological inhibitors and siRNAs. RESULTS: TNF-α induced phosphorylation of JNK and c-Jun was sustained by p38 inhibitors in monocytes, primary macrophages and FLS. Upregulation of Mip1α, Mip1ß and IL-8 mRNAs and protein were observed upon p38 inhibition. More importantly, inhibition of MK2, the substrate of p38 did not sustain JNK activation upon TNF-α activation and did not elevate Mip1α, Mip1ß and IL-8 chemokines as compared to TNF-α alone. In this study, TNF-α or IL-1ß induced JNK activation is sustained by p38 inhibition, resulting in enhanced chemokine secretion. CONCLUSIONS: Based on the suggested role of these chemokines in RA pathogenesis, the upregulation of these chemokines may provide an explanation for the lack of efficacy of p38 inhibitors in Phase II. The absence of any effect of MK2 inhibition in our models on this mechanism, while coming with similar efficacy on blocking p38, provides support for further investigations to reveal the potential of MK2 inhibition as a novel treatment of RA.

Stickler syndrome: an underdiagnosed disease. Report of a family.

PURPOSE: To report a family diagnosed with Stickler syndrome. To emphasize that early recognition of patients with Stickler syndrome could improve the visual outcome. METHODS: Case report. RESULTS: A 14 year old girl of Mahgrebian origin presented with a longstanding subtotal RRD in the right eye. Subsequently 6 family members in 3 generations have been identified with the same COL2A1 mutation. 4 eyes lost perception of light and 1 eye was enucleated. Stickler syndrome is the commonest inherited cause of rhegmatogenous retinal detachment (RRD). These tend to be complex and to occur at young age, frequently affecting both eyes. Other ocular features consist of high myopia, optically empty vitreous cavity, posterior radial paravascular lattice-type degeneration, cataract and glaucoma. Non-ocular findings include midface hypoplasia, musculoskeletal changes and hearing loss. In severe cases the disorder will readily be suspected. In mildly affected patients, clinical diagnosis can be quite difficult. Therefore, all family members of a Stickler patient should be offered molecular genetic testing. Stickler patients benefit from a multidisciplinary approach, including audiologic examination. They should be informed about the symptoms associated with retinal tears and retinal detachment and have priviliged access to the ophthalmic care unit. In case of RRD, vitrectomy is the preferred surgery. Prophylaxis of RRD in Stickler syndrome patients consisting of a 360 degrees peripheral cryotherapy or photocoagulation has been proposed. Practical guidelines for follow up or thresholds for initiating treatment have not been formulated. CONCLUSIONS: Stickler syndrome remains under-diagnosed. Hightened awareness of Stickler syndrome could improve visual outcome in affected individuals and makes genetic counseling possible

Targeted next-generation sequencing using a multigene panel in myeloid neoplasms: Implementation in clinical diagnostics.

INTRODUCTION: Detection of mutations in patients with myeloid neoplasms (MNs) has shown great potential for diagnostic and prognostic purposes. Next-generation sequencing (NGS) is currently implemented for the diagnostic profiling of the four major MN subgroups. METHODS: First, we validated the targeted NGS approach using the TruSight Myeloid panel. Next, we screened 287 patients with a clinical suspicion of MN and 61 follow-up patients with documented MN. RESULTS: Validation of the NGS workflow resulted in maximal precision, accuracy, sensitivity, and specificity for gene variants with an allele frequency of at least 5% and a minimal read depth of 300. In our diagnostic screen, we identified at least one somatic mutation in 89% of patients with proven MN. Of the 155 newly diagnosed MN cases, 126 (81%) showed at least one mutation, confirming clonality. Moreover, the co-occurrence of mutated genes in the different MN subentities facilitates their classification and justifies the diagnostic use of a pan-myeloid panel. Furthermore, several of these mutations provide additional prognostic information independently of traditional prognostic scoring systems. CONCLUSION: Pan-myeloid targeted NGS fits elegantly in the routine diagnostic approach of MNs allowing for an improved diagnosis, subclassification, and prognosis.

Clinical and genetic significance of unilateral Lisch nodules.

PURPOSE: Bilateral Lisch nodules are highly characteristic for neurofibromatosis type 1 (NF1). We wished to study the clinical and genetic implications of unilateral Lisch nodules. METHODS: Retrospective study of the clinical data of 59 patients who received genetic counselling for neurofibromatosis type 1 (NF1) or type 2 (NF2) and were examined at the department of ophthalmology. RESULTS: Unilateral Lisch nodules were observed in 4 cases: one child with NF1 initially presented unilateral Lisch nodules but developed bilateral Lisch nodules by the age of 9. In 2 cases segmental NF1 was the most probable diagnosis and in one case isolated Lisch nodules were observed. Of the 35 NF1 patients 28 ultimately developed bilateral Lisch nodules. Seven NF1 patients did not demonstrate the nodules. At follow-up no Lisch nodules were detected in 2 neurofibromatosis type 2 patients, in 4 patients in whom the diagnosis of NF1 remained doubtful and in 15 patients without NF1. CONCLUSION: Because isolated Lisch nodules are very rare, their presence warrants a thorough patient history and clinical examination to either confirm or exclude generalised or segmental neurofibromatosis type 1.

A low content in zeatin type cytokinins is not restrictive for the occurrence of G1/S transition in tobacco BY-2 cells.

Theories on the importance of cytokinins in G1/S transition control are manifold and contradictory. By establishing a double A(phi-PZ block, maximal synchronization of a BY-2 suspension culture was obtained to investigate the effect of cytokinin depletion on G1/S transition. Lovastatin was used as a specific inhibitor of cytokinin biosynthesis. Flow cytometry showed that the G1/S transition occurred regardless of the cytokinin drop. This observation indicates an extremely low dose requiry for that stage of the cell cycle. It is very likely that precisely the downregulation of zeatin type cytokinins matters for the G1/S transition to occur, since cytokinin addition at early G1 blocked the cycle at G1/S.

Benign intracranial hypertension as a cause of transient partial pituitary deficiency.

A male patient is reported with benign intracranial hypertension, who presented with three periods of partial pituitary deficiency, corresponding to episodes of headaches and papilledema. No radiological signs of the empty sella syndrome were observed. Since benign intracranial hypertension has been implicated in the development of the empty sella syndrome, it is postulated that the endocrine deficiency syndrome encountered in the empty sella syndrome can be provoked by chronic intracranial hypertension in itself and is not necessarily secondary to the anatomical changes occurring in the sellar region.

Apical dominance in Pssu-ipt-transformed tobacco.

In Pssu-ipt-transformed tobacco, apical dominance was released by defoliation of the upper nodes, while the apex remained intact. After defoliation, the concentration of cytokinins (CKs) increased whereas IAA remained constant, evoking an increase in the CK/IAA ratio in the buds. Moreover, defoliation resulted in a tremendous increase in the concentrations of aromatic amines (AAs): tyramine (TYR), phenethylamine (PEA) and an as yet unidentified compound. Although the total aliphatic monoamine and polyamine (PA) concentration remained constant, putrescine (PUT) and spermidine (SPD) concentrations in the axillary buds decreased, whereas the concentration of spermine (SPM) increased. Similar changes in PAs and AAs could be observed in the buds of untransformed SR1 plants after decapitation, whereas defoliation without removal of the apex had no effect. This is the first report on the possible involvement of PAs and AAs in apical dominance.

Sex steroids possess distinct stimulus properties in female and male mice.

Very few studies have investigated the aversive properties of sex steroids in animals. We studied these properties by testing oestradiol-3-benzoate, testosterone-propionate and progesterone in a conditioned taste aversion set-up, in intact female and male mice. Oestradiol-3-benzoate induced a taste aversion in both female and male mice; however, testosterone-propionate and progesterone had an effect only in females. These results show that sex steroids have intrinsic aversive properties. The different effects of the steroids in males and females cannot simply be explained by nausea induction or novelty.

Secondary closure of posterior continuous curvilinear capsulorhexis.

PURPOSE: To examine the hypothesis that removing the center of the posterior capsule would prevent posterior capsular opacification (PCO). SETTING: Department of Ophthalmology, University Hospital Antwerp, Belgium. METHODS: A posterior continuous curvilinear capsulorhexis (CCC) was done before intraocular lens (IOL) implantation in eyes at risk for PCO (uveitic, young adult), retinal detachment after neodymium:YAG (Nd:YAG) laser capsulotomy (highly myopic) or for cystoid macular edema (uveitic, diabetic) and in eyes in which the posterior capsule was opaque intraoperatively. The 51 eyes of 40 patients had a follow-up ranging from 6 months to 2 years. RESULTS: Four eyes (8%) developed partial closure of the posterior CCC without vision impairment; 6 eyes (12%) had total closure, of which 2 (4%) had a loss of two or more Snellen lines necessitating an Nd:YAG laser capsulotomy. CONCLUSION: Young adult eyes and eyes with underlying diabetic retinopathy or uveitis are at risk for total closure of the posterior CCC. Only young adult eyes required Nd:YAG laser capsulotomy after the posterior CCC.

The involvement of glucocorticoids in the acquired immobility response is dependent on the water temperature.

The Porsolt swim test was used to study the role of glucocorticoids in a simple learning paradigm. Two experiments were performed. In the first experiment, the stressfulness of the situation was manipulated by testing control, sham-operated and adrenalectomized mice at different water temperatures (20 degrees C, 25 degrees C, 30 degrees C and 35 degrees C). In the second experiment, control mice were injected with the glucocorticoid antagonist RU38486 (3.2 mg/kg, 10 mg/kg, 32 mg/kg); adrenalectomized mice were injected with the glucocorticoid agonists corticosterone (0.46 mg/kg, 1.0 mg/kg, 2.2 mg/kg) and dexamethasone (0.005 mg/kg, 0.05 mg/kg, 0.1 mg/kg). The results show that water temperature is a very important factor in the Porsolt swim test. It influences the overall behaviour of the animals and changes the involvement of glucocorticoids. At a water temperature of 25 degrees C, glucocorticoids play an important role in the retention of the immobility response; ADX mice are impaired, and this impairment can be ameliorated by corticosterone and dexamethasone injection. Furthermore, the impairment can be induced in control mice by RU38486. The effects observed at 25 degrees C were, however, not observable at 20 degrees C, 30 degrees C and 35 degrees C, which suggests, contrary to previous reports, that glucocorticoids do not play a universal role in retention processes.

Hereditary otovestibular dysfunction and Ménière's disease in a large Belgian family is caused by a missense mutation in the COCH gene.

OBJECTIVE: To report the clinical, auditory, and vestibular characteristics of a nonsyndromic otovestibular dysfunction in a large Belgian family caused by a missense mutation of the DFNA9 gene: COCH. STUDY DESIGN: Retrospective study of the clinical, audiologic, and vestibular data of 60 genetically affected cases. SETTING: Tertiary referral center. PATIENTS: All members of a Belgian kindred who carry the genetic (P51S) defect linked to the inherited hearing and vestibular impairment. INTERVENTIONS: Diagnostic otologic, audiometric, and vestibular analysis and imaging. MAIN OUTCOME MEASURES: Pure tone audiometry, supraliminary audiometry. and vestibular investigation. RESULTS: The autosomal dominant inherited impairment was characterized by peripheral degeneration of the inner ear, leading to total deafness and bilateral vestibular areflexia. CONCLUSIONS: The genetically affected persons of a Belgian family shared a progressive sensorineural hearing loss starting between the third and sixth decade. Vestibular symptoms started at about the same age as the hearing loss. The vestibular symptoms consisted of instability in darkness, a tendency to fall sideways, light-headiness, a drunken feeling, and attacks of vertigo. Most of the patients reported tinnitus, and half of them reported pressure in the ears. Clinically, 9 of the 60 patients met the criteria for definite Ménière's disease, and another 13 and 17 patients met the criteria for probable or possible Ménière's disease, respectively. All 9 were older than the age of 35, but only 1 was older than 55 years, so more than 30% of the patients were between 35 and 55 years old. A specific pattern could be recognized in the evolution of the otovestibular impairment. Under the age of 35 years, almost all the affected family members had normal hearing, whereas above the age of 55 years, the hearing loss was at least moderate, and vestibular hypofunction occurred. In between, there was a transition period of two to three decades, when deterioration of the cochleovestibular function occurred, with a temporary audiometric and vestibular asymmetry.

[Value of nutritional indicators for the prognosis of intrahospital mortality in children in Kivu]. / Valeur des indicateurs nutritionnels pour le pronostic de la mortalité intra-hospitalière chez les enfants du Kivu.

From 1986 to 1988, 1,129 children were hospitalized in Lwiro (South-Kivu, Zaïre) 3/4 of which were severely malnourished. Anthropometric, clinical and biological indicators were measured at admission. Observed mortality rate was 17.4%. Survival curves differ significantly for each anthropometric parameter measured at inclusion. In multivariate analysis, weight for age calculated with local reference or arm circumference is significantly associated with survival. The addition of serum albumin concentration to the multivariate model, shows this variable to be important. However, the use of an anthropometric indicator, such as weight for age or arm circumference is still important because it maintains an independent and significant effect on survival.

Serum albumin concentration, arm circumference, and oedema and subsequent risk of dying in children in central Africa.

OBJECTIVE: To measure the prognostic value of clinical, anthropometric, and biological indicators of protein energy malnutrition in hospitalised children. DESIGN: Hospital based follow up study from admission to discharge or death of a cohort of children. SETTING-Paediatric hospital in Zaire. SUBJECTS: 1129 children consecutively admitted between August 1986 and October 1988. MAIN OUTCOME MEASURES: Height, weight, arm circumference, skinfold thicknesses, serum albumin concentration, and mortality. RESULTS: Mortality was higher in wasted children and in those with a mid-upper arm circumference < 125 mm, a serum albumin concentration < 16 g/l, and oedema. After multivariate analysis, serum albumin concentration was the best predictor of subsequent risk of dying. Mid-upper arm circumference and oedema, however, still contributed considerably to evaluation of mortality. CONCLUSIONS: In this specific environment of central Africa an isolated clinical sign such as oedema is not enough to detect children with a high risk of dying among those admitted to paediatric wards with severe protein energy malnutrition. Measurement of additional indicators such as arm circumference and serum albumin concentration seems to be of crucial importance.

Primary posterior capsulorhexis in phacoemulsification: short term results.

Twenty-eight eyes were followed for at least 6 months after phacoemulsification, posterior capsulorhexis and intracapsular lensimplantation. No case of clinical significant macular edema, retinal tear or retinal detachment was noted during this period.

Unusual combination of night blindness and optic neuropathy after biliopancreatic bypass.

Night blindness and optic neuropathy were the presenting symptoms of an iatrogenic malabsorption syndrome in a 64-year old female. This case illustrates the necessity of lifelong vitamin supplementation after biliopancreatic bypass for morbid obesity.

Central retinal artery occlusion after back surgery: a case report.

Central retinal artery occlusion can be caused by excessive extrinsic pressure on the eyeball during surgery. It is a well-known and severe complication after elective back surgery. The authors report a case of central retinal artery occlusion in an adult after posterior lumbar fusion in which a rectangular headrest was used.

Secondary closure of posterior continuous circular capsulorhexis.

We examined the hypothesis that removing the center of the posterior capsule would reduce the risk for posterior opacification (PCO). We considered the prevalence of post-operative complications after PCCC like retinal detachment and cystoid macular edema, as found after Nd-YAG laser capsulotomy.