Modeling additive and non-additive effects in a hybrid population using genome-wide genotyping: prediction accuracy implications.

Hybrids are broadly used in plant breeding and accurate estimation of variance components is crucial for optimizing genetic gain. Genome-wide information may be used to explore models designed to assess the extent of additive and non-additive variance and test their prediction accuracy for the genomic selection. Ten linear mixed models, involving pedigree- and marker-based relationship matrices among parents, were developed to estimate additive (A), dominance (D) and epistatic (AA, AD and DD) effects. Five complementary models, involving the gametic phase to estimate marker-based relationships among hybrid progenies, were developed to assess the same effects. The models were compared using tree height and 3303 single-nucleotide polymorphism markers from 1130 cloned individuals obtained via controlled crosses of 13 Eucalyptus urophylla females with 9 Eucalyptus grandis males. Akaike information criterion (AIC), variance ratios, asymptotic correlation matrices of estimates, goodness-of-fit, prediction accuracy and mean square error (MSE) were used for the comparisons. The variance components and variance ratios differed according to the model. Models with a parent marker-based relationship matrix performed better than those that were pedigree-based, that is, an absence of singularities, lower AIC, higher goodness-of-fit and accuracy and smaller MSE. However, AD and DD variances were estimated with high s.es. Using the same criteria, progeny gametic phase-based models performed better in fitting the observations and predicting genetic values. However, DD variance could not be separated from the dominance variance and null estimates were obtained for AA and AD effects. This study highlighted the advantages of progeny models using genome-wide information.

Survival of Coelaenomenodera lameensis (Coleoptera: Chrysomelidae) in Relation to the Physical Characteristics of Different Oil Palm (Elaeis sp.) Breeding Populations.

The edibility of different Elaeis sp. breeding populations present in Benin was tested for the leaf miner Coelaenomenodera lameensis Berti (Coleoptera: Chrysomelidae), a major oil palm pest in Africa. Experiments carried out in sleeves revealed the oviposition capacities of females and the mortality rates for the different developmental stages by comparing the populations found on two breeding populations of Elaeis oleifera (HBK) Cortes, four of Elaeis guineensis Jacquin and four (E. guineensis × E. oleifera) × E. guineensis backcrosses. Females laid their eggs similarly on all breeding populations, with a preference for the E. guineensis La Mé origin. The average hatching rate reached 80% for the La Mé origin as opposed to 28% for the Deli origin. The mortality rates for the larval instars were greater on E. oleifera, on certain backcrosses and on the Deli origin of E. guineensis. Development at the second- and third- larval instars was the most affected, with a mortality rate of three to five times greater than that seen on La Mé. Epidermis and cuticle measurements indicated which breeding populations were suitable or unsuitable for the development of C. lameensis. E. guineensis, with its thin epidermis (12 µm) and cuticle (2 µm), proved to be highly susceptible to C. lameensis attacks. On the other hand, E. oleifera, which is very resistant, exhibited a thicker epidermis (17 µm) and cuticle (4 µm). The breeding populations were thus classified according to the positive or negative influence they exerted on the insect's egg laying and feeding.

Improving palm oil quality through identification and mapping of the lipase gene causing oil deterioration.

The oil palm fruit mesocarp contains high lipase activity that increases free fatty acids and necessitates post-harvest inactivation by heat treatment of fruit bunches. Even before heat treatment the mesocarp lipase activity causes consequential oil losses and requires costly measures to limit free fatty acids quantities. Here we demonstrate that elite low-lipase lines yield oil with substantially less free fatty acids than standard genotypes, allowing more flexibility for post-harvest fruit processing and extended ripening for increased yields. We identify the lipase and its gene cosegregates with the low-/high-lipase trait, providing breeders a marker to rapidly identify potent elite genitors and introgress the trait into major cultivars. Overall, economic gains brought by wide adoption of this material could represent up to one billion dollars per year. Expected benefits concern all planters but are likely to be highest for African smallholders who would be more able to produce oil that meets international quality standards.

Rigorous analysis of highly tunable cylindrical transverse magnetic mode re-entrant cavities.

Cylindrical re-entrant cavities are unique three-dimensional structures that resonate with their electric and magnetic fields in separate parts of the cavity. To further understand these devices, we undertake rigorous analysis of the properties of the resonance using "in-house" developed Finite Element Method (FEM) software capable of dealing with small gap structures of extreme aspect ratio. Comparisons between the FEM method and experiments are consistent and we illustrate where predictions using established lumped element models work well and where they are limited. With the aid of the modeling we design a highly tunable cavity that can be tuned from 2 GHz to 22 GHz just by inserting a post into a fixed dimensioned cylindrical cavity. We show this is possible, as the mode structure transforms from a re-entrant mode during the tuning process to a standard cylindrical transverse magnetic mode.

Precise phase synchronization of a cryogenic microwave oscillator.

We developed a novel technique for accurate phase synchronization of microwave oscillators based on sapphire dielectric resonators cooled to liquid nitrogen temperature. The achieved quality of phase synchronization (a few milliradians) enables the accurate measurements of extremely weak phase fluctuations expected from the next generation of ultralow phase noise microwave oscillators.

Intramuscular interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) shares immunologic features with multiple sclerosis (MS). Because IM interferon beta-1a (IM IFNbeta-1a) is an effective and safe treatment for MS, we conducted a dose-ranging efficacy study of IFNbeta-1a in patients with CIDP. METHODS: Adults with IV immunoglobulin (IVIg)-dependent CIDP (n = 67) were enrolled in this 32-week double-blind trial and randomized to IM IFNbeta-1a. Patients received 30 microg once weekly plus placebo (n = 12), IM IFNbeta-1a 60 microg once weekly plus placebo (n = 11), IM IFNbeta-1a 30 microg twice weekly (n = 11), IM IFNbeta-1a 60 microg twice weekly (n = 11), or placebo twice weekly (n = 22). Participants were maintained on IVIg through week 16, when IVIg was discontinued. Patients who worsened were restarted on IVIg. The primary outcome was total IVIg dose (g/kg) administered from week 16 to 32. RESULTS: There was no difference in total IVIg dose administered after week 16 for patients treated with IFNbeta-1a (1.20 g/kg) compared with placebo (1.34 g/kg; p = 0.75). However, exploratory analyses suggested IFNbeta-1a significantly reduced total dose of IVIg compared with placebo for participants who required either high-dose IVIg (>0.95 g/kg per month) or had greater weakness at baseline (Medical Research Council sum score <51). Adverse events included flu-like symptoms, headache, and fatigue in the IFNbeta-1a groups. CONCLUSIONS: Interferon beta-1a (IFNbeta-1a) therapy did not provide significant benefit over IV immunoglobulin (IVIg) therapy alone for patients with chronic inflammatory demyelinating polyradiculoneuropathy. However, IFNbeta-1a might be beneficial for patients with more severe disability or those needing high doses of IVIg. LEVEL OF EVIDENCE: This study was designed to provide Class I evidence for the safety and efficacy of IM IFNbeta-1a in the treatment of CIDP but has been subsequently classified as Class II due to a >20% patient dropout rate. Thus, this randomized, controlled clinical trial provides Class II evidence of no effect on primary and secondary endpoints of 4 dosage regimens of IM IFNbeta-1a added to IVIg in persons with CIDP.

Long-term effects of intravenous immunoglobulin in CIDP.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired demyelinating disease of the peripheral nervous system characterized by muscle weakness, areflexia or hyporeflexia, and sensory disturbances. Although short-term efficacy of intravenous immunoglobulin (IVIg) has been demonstrated in randomized-controlled trials, the data pertaining to long-term outcome in CIDP are limited. Consequently, the aim of the present study was to assess the long-term effects of IVIg on neurophysiological parameters in CIDP. METHODS: Neurophysiological records from 11 CIDP patients, treated with IVIg for 12 months, were reviewed. Nerve conduction studies were assessed at baseline, 1-year, and last follow-up. RESULTS: There was a significant reduction in the frequency of conduction blocks (pre-treatment nerve segments affected 61%; last follow-up 39%, P<0.01) and a reduction in ongoing axonal loss (pre-treatment regions with spontaneous activity, 47%; post-treatment 29%, P<0.01) with IVIg treatment. Further, there was significant improvement in sensory nerve conduction studies with IVIg treatment (sensory amplitudes reduced pre-treatment, 90% nerves tested; post-treatment, 62%, P<0.01). CONCLUSIONS: The present study suggests that long-term IVIg maintenance therapy improves neurophysiological parameters in CIDP. However, CIDP patients remain IVIg dependent and new conduction blocks may develop. SIGNIFICANCE: The present study suggests that long-term IVIg maintenance therapy improves neurophysiological parameters in CIDP, possibly by reducing the immune response and thereby fostering nerve healing.

[Multifocal motor neuropathies with conduction block: long-term follow-up of ten patients treated with IVIg]. / Neuropathie motrice multifocale avec blocs de conduction: suivi à long terme de 10 patients traités par IgIV.

UNLABELLED: Multifocal motor neuropathy (MMN) with conduction block responds to high-dose i.v. polyvalent immunoglobulins (IVIg) over the short term, but several studies have demonstrated a long-term increase in the degree of axonal degeneration and the number of conduction blocks, factors indicating a poor prognosis. The objective of this study was to evaluate the long-term effect of IVIg on clinical and neurophysiological parameters. METHODS: We reviewed the records of ten patients who had initially responded well to IVIg and received regular, long-term treatment. The parameters studied were muscular strength, motor function status (modified Rankin scale), as well as the number and progression of conduction blocks and the degree of axonal degeneration. Patients were followed up for a mean of 7.25 years (range, 3.5-12). They were all initially treated with 2 g IgIV/kg in 5 days every 4 weeks for 3 months. Maintenance therapy was administered every 4 weeks with dose adjustment to prevent muscular strength deterioration. RESULTS: We noted a significant and persistent improvement in muscular strength and in the Rankin motor function score over the long term, with no escape phenomenon. The number of conduction blocks and the degree of axonal degeneration decreased markedly. CONCLUSION: IVIg treatment remains effective over the long term in MMN. These conclusions differ from those of other authors in earlier studies, but our patients were treated with significantly higher doses of IVIg. These results have important implications for long-term treatment of patients with MMN.

Facial onset sensory and motor neuronopathy (FOSMN syndrome): a novel syndrome in neurology.

A 'syringomyelia-like' syndrome has been infrequently reported in neurological disorders such as Tangiers disease and lepromatous leprosy. This study reports a novel 'syringomyelia-like' syndrome in four adult male patients, which we have termed facial onset sensory and motor neuronopathy, or FOSMN syndrome, that appears to have a neurodegenerative aetiology. Clinical, neurophysiological and pathological data of four patients were reviewed, including the autopsy in one patient. Four male patients (mean age at onset 43), initially developed paraesthesiae and numbness in a trigeminal nerve distribution, which slowly progressed to involve the scalp, neck, upper trunk and upper limbs in sequential order. Motor manifestations, including cramps, fasciculations, dysphagia, dysarthria, muscle weakness and atrophy developed later in the course of the illness. Neurophysiological findings revealed a generalized sensory motor neuronopathy of caudally decreasing severity in all four patients. Autopsy in one patient disclosed loss of motoneurons in the hypoglossal nucleus and cervical anterior horns, along with loss of sensory neurons in the main trigeminal sensory nucleus and dorsal root ganglia. FOSMN syndrome appears to be a slowly progressive neurodegenerative disorder, whose pathogenesis remains to be determined.

Thromboembolic complications of intravenous immunoglobulin treatment.

Intravenous immunoglobulin (IVIg) preparations are increasingly being used in the treatment of neuroautoimmune diseases. Although for most part this treatment is safe, serious side effects such as thromboembolic events have been reported. We report on 7 patients who suffered a thromboembolic event while being treated with IVIg. Four patients suffered a stroke or transient ischemic attack, 1 an inferior wall myocardial infarction, 1 a deep venous thrombosis, and 1 a retinal artery infarct. The age range of the patients was 57-81 and most had underlying risk factors, such as hypertension, hypercholesterolemia, atrial fibrillation, history of vascular disease and stroke, and deep venous thrombosis. Three patients received multiple IVIg infusions before suffering a thromboembolic complication. Therefore, the clinicians should be vigilant about the possibility of thromboembolic complications with each IVIg infusion and be especially judicious with the use of IVIg in patients with underlying risk factors.

Pure motor mononeuropathy with distal conduction block: an unusual presentation of multifocal motor neuropathy with conduction blocks.

OBJECTIVE: To report an hitherto undescribed presentation of Motor Neuropathy with Multifocal Conduction Block (MMNCB). METHODS: Description of two patients presenting with complete paralysis of the 3 heads of the trapezius muscle (case one) and progressive weakness of finger extension (case 2). RESULTS: Nerve conduction studies (NCS) established that the corresponding nerves were distally inexcitable. In the affected muscles, no voluntary activity was elicited in both patients with spontaneous activity noted in patient 2. Systematic NCSs documented an asymptomatic, partial conduction block (CB) in a median nerve forearm segment in both patients. Neurophysiological follow-up after a dramatic response to intravenous immunoglobulins demonstrated recovery of the initially unobtainable motor responses. CONCLUSIONS: This indicates that a complete, distal CB of the motor fibers destined to the trapezius muscle in patient 1, and to the extensor indicis proprius in patient 2, had caused the heralding deficits. SIGNIFICANCE: These findings underscore the possibility of distal CB in this disorder and the need for extensive NCSs, including asymptomatic nerves, for an accurate diagnosis.

Interferon beta-1a as an investigational treatment for CIDP.

A prospective, multicenter, open-label study was conducted to determine the safety and efficacy of intramuscular (IM) interferon beta-1a (IFNbeta-1a) (Avonex) for treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eligible patients received IM IFNbeta-1a 30 microg once weekly for 6 months. Safety and tolerability were evaluated by reporting of adverse events, measurement of vital signs, and results of blood chemistry, hematology, and urinalysis. The primary efficacy end points were changed from baseline to month 6 on a quantitative Neurologic Disability Score (NDS), a clinical grading (CG) scale, and grip strength (GS) measures. Electrophysiologic measurements were performed at baseline and month 6. A total of 20 treatment-resistant patients with CIDP were enrolled in the study. The tolerability of IFNbeta-1a in patients with CIDP was similar to that seen with its use in MS. There were no serious adverse events, and no patients discontinued treatment due to adverse events. Seven patients (35%) showed clinical improvement, 10 (50%) had stable disease, and 3 (15%) continued to deteriorate. Significant improvements from baseline were observed in NDS in both the intent-to-treat and per protocol analyses (p=0.0005). For CG, significant improvement from baseline was observed in the per protocol analysis (p<0.05) but not in the intent-to-treat analysis. There was no significant effect of treatment on GS. Clinical improvement was not dependent on age, gender, clinical form of CIDP, or duration of symptoms. Electrophysiologic data showed improvements in mean median, ulnar, and tibial motor nerve potential areas. There was no correlation between clinical improvement and electrophysiologic data. The promising results of this study, especially given the refractory nature of the patient population, suggest that a larger placebo-controlled study should be performed to further evaluate the efficacy of IM IFNbeta-1a for the treatment of CIDP.

Multiple Symmetric Lipomatosis (Madelung's Disease) Caused by the MERRF (A8344G) Mutation: A Report of Two Cases and Review of the Literature.

Multiple symmetric lipomatosis (MSL) was first described by Brodie in 1846 and is characterized by accumulation of non-encapsulated lipomas in the cervical-cranial-thoracic region. Alcohol consumption is regarded as essential in lipoma development by some. Mitochondrial dysfunction was first reported in 1991. Since then, there has been controversy regarding etiology of MSL, with a number of studies supporting and some refuting the role of mitochondrial dysfunction. We report on 2 cases of MSL with pathologic (ragged-red fibers) and molecular (A8344G mutation) features of mitochondrial dysfunction. A literature review revealed that mitochondrial gene dysfunction was evident in 28% of MSL cases. Furthermore, the MERRF mutation (A8344G) was detected in 16% and mitochondrial gene deletions in 12% of MSL cases. Therefore, clinicians need to be vigilant of the fact that a significant proportion of the MSL phenotype results from mitochondrial gene mutations and/or deletions.

Using posturography to detect unsteadiness in 13 patients with peripheral neuropathy: a pilot study.

Our aims were to use posturography to see if sway pattern differed between patients with large-fiber peripheral neuropathy and normal control subjects and, if it did, to compare posturography with conventional electromyography (EMG) as screening tools for large-fiber peripheral neuropathy. Thirteen patients who came to our neurophysiology laboratory with a preliminary diagnosis of peripheral neuropathy (made by their referring physicians) were compared with 7 nonmatched control subjects. All subjects received a neurologic examination and underwent posturography and conventional EMG. Results of posturography and conventional EMG were compared. Posturography showed abnormal sway patterns only in patients who had EMG abnormalities consistent with large-fiber peripheral neuropathy. These sway patterns differed significantly from those of the control subjects. Posturography seems to be a useful and well-tolerated screening test for patients with a history suggestive of peripheral neuropathy, and results of posturography agree with those of conventional EMG. Moreover, posturography directly measures increased sway in these patients and may be used as a more direct screen for risk of falls in this population.

Analysis of the rutile-ring method of frequency-temperature compensating a high-Q whispering gallery sapphire resonator.

The rutile-ring method of dielectrically frequency-temperature compensating a high-Q whispering gallery (WG) sapphire resonator is presented. Two and three-dimensional finite element (FE) analysis has been implemented to design and analyze the performance of such resonators, with excellent agreement between theory and experiment. A high-Q factor of 30 million at 13 GHz and compensation temperature of 56 K was obtained. It is shown the frequency-temperature compensation can occur either because the rutile adds a small perturbation to the sapphire resonator or because of a mode interaction with a resonant mode in the rutile. The characteristics of both of these methods are described, and it is shown that for high frequency stability, it is best to compensate perturbatively.

Compact, high-Q, zero temperature coefficient, TE011 sapphire-rutile microwave distributed Bragg reflector resonators.

Some novel new resonator designs based on the distributed Bragg reflector are presented. The resonators implement a TE011 resonance in a cylindrical sapphire dielectric, which is confined by the addition of rutile and sapphire dielectric reflectors at the end faces. Finite element calculations are utilized to optimize the dimensions to obtain the highest Q-factors and zero frequency-temperature coefficient for a resonator operating near 0 degree C. We show that a Q-factor of 70,000 and 65,000 can be achieved with and without the condition of zero frequency-temperature coefficients, respectively.

Median neuropathy at the wrist: diagnostic utility of clinical findings and an automated electrodiagnostic device.

Clinical findings have limited value in predicting electrophysiologically confirmed median neuropathy at the wrist (MNW). To determine the value of clinical findings and an automated electrophysiologic neurodiagnostic device (AEND) in diagnosing MNW, we studied two groups of 75 consecutive patients (an initial group and a validation group, 150 total) referred to an academic electrophysiology laboratory for upper extremity complaints. The definitive standard for MNW was the neurologist's diagnosis after formal clinical and electrodiagnostic evaluation. The neurologist was blinded to the results of the AEND (NC-Stat, NeuroMetrix, Inc). In the validation group, the AEND yielded a distal motor latency (DML) in 97% of hands with a conventional motor response, and the correlation of the AEND DML with the conventional DML was 0.94 (P < 0.001). Of 248 symptomatic hands, the neurologist diagnosed 117 (47%) with MNW. At 90% specificity, the AEND DML had a sensitivity of 86% for MNW. Age, body mass index, sensory symptoms in digits 1 to 3, and nocturnal awakening were independent clinical predictors of MNW. Each 1-msec increase in the adjusted AEND DML was independently associated with an OR of 298 (95% confidence interval, 40 to 2233) for MNW. Each 1-msec increase in the F-wave latency was independently associated with an OR of 2.6 (95% confidence interval, 1.3 to 4.9) for MNW. Compared with a model based solely on clinical variables, an algorithm including symptom variables plus the AEND DML had an odds ratio for correct diagnostic classification of 6.3 (95% confidence interval, 3.8 to 12.3). The sensitivity at 90% specificity improved from 40% for the clinical model to 86% for the model with DML. A practical method for integrating clinical and electrophysiologic findings to assess the risk of MNW was proposed. This method correctly stratified 79% of control and MNW patients into very low- and high-risk groups, respectively. We concluded that MNW diagnosis is significantly improved with an AEND.

High-Q whispering gallery traveling wave resonators for oscillator frequency stabilization.

Usually a frequency-stabilized standing wave resonator-oscillator incorporating a resonator as a frequency discriminator requires a circulator to separate the injected and reflected wave, A ferrite circulator is a noisy device and can limit the phase noise or frequency stability. Moreover, we show that the noise in a circulator varies, and detailed low noise measurements are necessary to choose an appropriate quiet circulator. Thus, by realizing a configuration that does not require a circulator, an improvement in performance and reliability can be obtained. A solution to this problem is to design a high-Q whispering gallery traveling wave (WGTW) resonator. This device naturally separates the injected and reflected wave in the same way as a ring cavity at optical frequencies, without degrading the frequency discrimination. Q-factor measurements of a WGTW sapphire resonator are presented, along with a derivation of critical parameters to maximize the frequency discrimination. New measurements of noise in ferrite circulators and isolators have also been made, which is followed with a discussion on oscillator design.