Optimising seed processing techniques to improve germination and sowability of native grasses for ecological restoration.

Grasslands across the globe are undergoing expansive degradation due to human impacts and climate change. If restoration of degraded native grassland is to be achieved at the scale now required, cost-effective means for seed-based establishment of grass species is crucial. However, grass seeds present numerous challenges associated with handling and germination performance that must be overcome to improve the efficiency of seeding. Previous research has demonstrated that complete removal of the palea and lemma (husk) maximises germination performance, hence we investigated the effects of complete husk removal on seed handling and germination of four temperate Australian grass species. Three techniques were tested to remove the husk - manual cleaning, flaming or acid digestion (the latter two followed by a manual cleaning step); these techniques were refined and adapted to the selected species, and germination responses were compared. The complete removal of the husk improved seed handling and sowability for all species. Germination was improved in Microlaena stipoides by 19% and in Rytidosperma geniculatum by 11%. Of the husk removal methods tested, flaming was detrimental to seed germination and fatal for one species (R. geniculatum). Compared to manual cleaning, sulphuric acid improved the overall efficacy of the cleaning procedure and increased germination speed (T50) in Austrostipa scabra, Chloris truncata and M. stipoides, and improved final germination in R. geniculatum by 13%. The seed processing methods developed and tested in the present study can be applied to grass species that present similar handling and germination performance impediments. These and other technological developments (seed coating and precision sowing) will facilitate more efficient grassland restoration at large scale.

Evidence of iteroparity in the widely distributed diadromous fish inanga Galaxias maculatus and potential implications for reproductive output.

Gaps in understanding variability among populations of inanga Galaxias maculatus in the timing of reproduction were addressed in southern New Zealand (NZ), where G. maculatus constitutes a declining fishery. Reproductive activity was delayed by 1 month on the west coast compared with the east coast and the west coast spawning season was prolonged into winter. The evidence for post-spawning survival of some fish was unequivocal from histological studies. These older and larger fish contributed disproportionately to egg production. Estimates of fecundity were considerably lower than those previously calculated for NZ populations. The importance of quality habitats being available during critical life history periods are highlighted. It was apparent that some streams supported fish that were larger and in better condition and that this translated into greatly increased fecundity. Future research should focus on whether this is a legacy of these fish experiencing better pre-settlement marine habitat as larvae, or higher quality instream habitat enhancing the growth and development of adults.

Parental environment changes the dormancy state and karrikinolide response of Brassica tournefortii seeds.

BACKGROUND AND AIMS: The smoke-derived chemical karrikinolide (KAR(1)) shows potential as a tool to synchronize the germination of seeds for weed management and restoration. To assess its feasibility we need to understand why seeds from different populations of a species exhibit distinct responses to KAR(1). Environmental conditions during seed development, known as the parental environment, influence seed dormancy so we predicted that parental environment would also drive the KAR(1)-responses of seeds. Specifically, we hypothesized that (a) a common environment will unify the KAR(1)-responses of different populations, (b) a single population grown under different environmental conditions will exhibit different KAR(1)-responses, and (c) drought stress, as a particular feature of the parental environment, will make seeds less dormant and more responsive to KAR(1). METHODS: Seeds of the weed Brassica tournefortii were collected from four locations in Western Australia and were sown in common gardens at two field sites, to test whether their KAR(1)-responses could be unified by a common environment. To test the effects of drought on KAR(1)-response, plants were grown in a glasshouse and subjected to water stress. For each trial, the germination responses of the next generation of seeds were assessed. KEY RESULTS: The KAR(1)-responses of seeds differed among populations, but this variation was reduced when seeds developed in a common environment. The KAR(1)-responses of each population changed when seeds developed in different environments. Different parental environments affected germination responses of the populations differently, showing that parental environment interacts with genetics to determine KAR(1)-responses. Seeds from droughted plants were 5 % more responsive to KAR(1) and 5 % less dormant than seeds from well-watered plants, but KAR(1)-responses and dormancy state were not intrinsically linked in all experiments. CONCLUSIONS: The parental environment in which seeds develop is one of the key drivers of the KAR(1)-responses of seeds.

Familial Alzheimer's disease and inherited prion disease in the UK are poorly ascertained.

AIMS: To ascertain the frequency and geographical distribution of patients diagnosed with known genetic causes of Alzheimer's disease (AD) and inherited prion disease (IPD) in the UK 2001-2005. By comparison with frequencies predicted from published population studies, to estimate the proportion of patients with these conditions who are being accurately diagnosed. METHODS: All the positive diagnostic test results (from both genetic testing centres) were identified for mutations in presenilin-1 (PSEN1), presenilin-2 (PSEN2), amyloid precursor protein (APP) and prion protein genes (PRNP) for patients resident in the UK in a 5 year period. The variation in the incidence of mutation detection between UK regions was assessed with census population data. Published studies of the genetic epidemiology of familial early onset AD (EOAD) were reviewed to produce estimates of the number of patients in the UK that should be detected. RESULTS: The rate of detection of EOAD and IPD varied very significantly and consistently between regions of the UK with low rates of detection in Northern and Western Britain (72% less detection in these regions compared with Central and Southeast Britain). The estimates from population studies further suggest a greater number of patients with EOAD than are diagnosed by genetic testing throughout the UK. CONCLUSIONS: It is likely that patients with EOAD and IPD are not being recognised and referred for testing. With the prospect of meaningful disease modifying therapeutics for these diseases, this study highlights an issue of relevance to neurologists and those planning for provision of National Health Services.

Long-term trends in carpal tunnel syndrome.

OBJECTIVE: To assess temporal trends in carpal tunnel syndrome (CTS) incidence, surgical treatment, and work-related lost time. METHODS: Incident CTS and first-time carpal tunnel release among Olmsted County, Minnesota, residents were identified using the medical records linkage system of the Rochester Epidemiology Project; 80% of a sample were confirmed by medical record review. Work-related CTS was identified from the Minnesota Department of Labor and Industry. RESULTS: Altogether, 10,069 Olmsted County residents were initially diagnosed with CTS in 1981-2005. Overall incidence (adjusted to the 2000 US population) was 491 and 258 per 100,000 person-years for women vs men (p < 0.0001) and 376 per 100,000 for both sexes combined. Adjusted annual rates increased from 258 per 100,000 in 1981-1985 to 424 in 2000-2005 (p < 0.0001). The average annual incidence of carpal tunnel release surgery was 109 per 100,000, while that for work-related CTS was 11 per 100,000. An increase in young, working-age individuals seeking medical attention for symptoms of less severe CTS in the early to mid-1980s was followed in the 1990s by an increasing incidence in elderly people. CONCLUSIONS: The incidence of medically diagnosed carpal tunnel syndrome (CTS) accelerated in the 1980s. The cause of the increase is unclear, but it corresponds to an epidemic of CTS cases resulting in lost work days that began in the mid-1980s and lasted through the mid-1990s. The elderly present with more severe disease and are more likely to have carpal tunnel surgery, which may have significant health policy implications given the aging population.

Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

The clinical and radiologic impact of natalizumab (Tysabri) as therapy for multiple sclerosis (MS) is assessed. On the basis of Class I evidence, natalizumab has been demonstrated to reduce measures of disease activity and to improve measures of disease severity in patients with relapsing-remitting (RR) MS (Level A). The relative efficacy of natalizumab compared to current disease-modifying therapies cannot be defined accurately (Level U). Similarly, the value of natalizumab in the treatment of secondary progressive (SP) MS is unknown (Level U). The value of combination therapy using natalizumab and interferon in the treatment of RRMS is also unknown (Level U). There is an increased risk of developing progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients (Level A for combination therapy, Level C for monotherapy) and possibly an increased risk of other opportunistic infections (Level C). The PML risk in a pooled clinical trial cohort has been estimated to be 1 person for every 1,000 patients treated for an average of 17.9 months, although this figure could change in either direction with more experience with the drug.

Neutralizing antibodies to interferon beta: assessment of their clinical and radiographic impact: an evidence report: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

The clinical and radiologic impact of developing neutralizing antibodies (NAbs) to interferon beta (IFNbeta) while on this therapy for multiple sclerosis (MS) is assessed. On the basis of Class II and III evidence, it is concluded that treatment of patients with MS with IFNbeta (Avonex, Betaseron, or Rebif) is associated with the production of NAbs (Level A). NAbs in the serum are probably associated with a reduction in the radiographic and clinical effectiveness of IFNbeta treatment (Level B). In addition, the rate of NAb production is probably less with IFNbeta-1a treatment than with IFNbeta-1b treatment, although the magnitude and persistence of this difference is difficult to determine (Level B). Finally, it is probable that there is a difference in seroprevalence due to variability in the dose of IFNbeta injected or in the frequency or route of its administration (Level B). Regardless of the explanation, it seems clear that IFNbeta-1a (as it is currently formulated for IM injection) is less immunogenic than the current IFNbeta preparations (either IFNbeta-1a or IFNbeta-1b) given multiple times per week subcutaneously (Level A). However, because NAbs disappear in some patients even with continued IFNbeta treatment (especially in patients with low titers), the persistence of this difference is difficult to determine (Level B). Although the finding of sustained high-titer NAbs (>100 to 200 NU/mL) is associated with a reduction in the therapeutic effects of IFNbeta on radiographic and clinical measures of MS disease activity, there is insufficient information on the utilization of NAb testing to provide specific recommendations regarding when to test, which test to use, how many tests are necessary, or which cutoff titer to apply (Level U).

Syncope associated with pain as the presenting feature of neck malignancy: failure of cardiac pacemaker to prevent attacks in two cases.

Two patients are described in whom syncope was the presenting clinical feature of an undiagnosed neck malignancy. Both patients also had attacks associated with paroxysms of severe neck pain. Neither patient responded to cardiac pacing.

Optic chiasm enhancement associated with giant aneurysm and yttrium treated pituitary adenoma.

A patient with a history of pituitary tumour treated with yttrium 29 years before presented with an asymmetrical chiasmal neuropathy. Magnetic resonance imaging showed a partially thrombosed giant aneurysm of the right internal carotid artery, with enhancement of the chiasm and right optic tract adjacent to the aneurysm. It was thought that, in addition to the effects of compression, a peri-aneurysmal inflammatory reaction had developed, causing breakdown of the blood-brain barrier and consequent inflammatory changes in the optic chiasm. High dose steroid treatment led to significant improvement in vision within two weeks. Steroids may have a role in the acute preservation of vision in similar cases, as well as in cases of deterioration following coiling or embolisation of aneurysms where thrombosis within the aneurysm has been induced.

Monitoring hydrate formation and dissociation in sandstone and bulk with magnetic resonance imaging.

Magnetic resonance imaging (MRI) has been shown to be a very effective tool for monitoring the formation and dissociation of hydrates because of the large intensity contrast between the images of the liquid components and the solid hydrate. Tetrahydrofuran/water hydrate was used because the two liquid components are miscible and form hydrate at ambient pressure. These properties made this feasibility study proceed much faster than using methane/water, which requires high pressure to form the hydrate. The formation and dissociation was monitored first in a THF/water-saturated Berea sandstone plug and second in the bulk. In both cases it appeared that nucleation was needed to begin the formation process, i.e., the presence of surfaces in the sandstone and shaking of the bulk solution. Dissociation appeared to be dominated by the rate of thermal energy transfer. The dissociation temperature of hydrate formed in the sandstone plug was not significantly different from the dissociation temperature in bulk.

Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To provide an evidence-based statement to guide physicians in the management of Guillain-Barré syndrome (GBS). METHODS: Literature search and derivation of evidence-based statements concerning the use of immunotherapy were performed. RESULTS: Treatment with plasma exchange (PE) or IV immunoglobulin (IVIg) hastens recovery from GBS. Combining the two treatments is not beneficial. Steroid treatment given alone is not beneficial. RECOMMENDATIONS: 1) PE is recommended for nonambulant adult patients with GBS who seek treatment within 4 weeks of the onset of neuropathic symptoms. PE should also be considered for ambulant patients examined within 2 weeks of the onset of neuropathic symptoms; 2) IVIg is recommended for nonambulant adult patients with GBS within 2 or possibly 4 weeks of the onset of neuropathic symptoms. The effects of PE and IVIg are equivalent; 3) Corticosteroids are not recommended for the management of GBS; 4) Sequential treatment with PE followed by IVIg, or immunoabsorption followed by IVIg is not recommended for patients with GBS; and 5) PE and IVIg are treatment options for children with severe GBS.

The frequency of carpal tunnel syndrome in computer users at a medical facility.

A survey was done of employees who were identified as frequent computer users. Although 29.6% of the employees reported hand paresthesias, only 27 employees (10.5%) met clinical criteria for carpal tunnel syndrome, and in 9 (3.5%) the syndrome was confirmed by nerve conduction studies. Affected and unaffected employees had similar occupations, years using a computer, and time using the computer during the day. The frequency of carpal tunnel syndrome in computer users is similar to that in the general population.

Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. BACKGROUND: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. METHODS: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? RECOMMENDATIONS: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke--AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). CONCLUSIONS: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.

Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. METHODS: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. RESULTS: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. RECOMMENDATIONS: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia.

Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To define and investigate key issues in the management of dementia and to make literature-based treatment recommendations. METHODS: The authors searched the literature for four clinical questions: 1) Does pharmacotherapy for cognitive symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for noncognitive symptoms improve outcomes in patients with dementia? 3) Do educational interventions improve outcomes in patients and/or caregivers? 4) Do other nonpharmacologic interventions improve outcomes in patients and/or caregivers? RESULTS: Cholinesterase inhibitors benefit patients with AD (Standard), although the average benefit appears small; vitamin E likely delays the time to clinical worsening (Guideline); selegiline, other antioxidants, anti-inflammatories, and estrogen require further study. Antipsychotics are effective for agitation or psychosis in patients with dementia where environmental manipulation fails (Standard), and antidepressants are effective in depressed patients with dementia (Guideline). Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to nursing home placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline).

Lack of correlation between in vitro inhibition of CYP3A-mediated metabolism by a PPAR-gamma agonist and its effect on the clinical pharmacokinetics of midazolam, an in vivo probe of CYP3A activity.

RG 12525 (2-[[4-[[2-(1H-tetrazole-5-ylmethyl)phenyl]methoxy]phenoxy]methyl] quinolone) is a novel peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist. In vitro microsomal inhibition assays indicated that RG 12525 is a potent inhibitor of CYP3A4, with a Ki value of 0.5 microM. With the conservative assumption that the total plasma concentration of drug was available to metabolic enzymes following RG 12525 oral administration, marked inhibition of CYP3A4 was expected to substantially reduce the systemic clearance of compounds metabolized by this enzyme. The possibility also existed for inhibition of intestinal and hepatic CYP3A4 by RG 12525 to reduce "first-pass" metabolism and increase absolute bioavailability of CYP3A4 substrates orally coadministered. Consequently, an in vivo drug-drug interaction study was performed to evaluate the effects of orally administered RG 12525 on in vivo CYP3A4 activity in healthy male subjects. The pharmacokinetics of oral midazolam, a probe for intestinal and hepatic CYP3A activity, was not influenced by either the low (100 mg qd for 4 days) or high (600 mg qd for4 days) RG 12525 dosing regimen despite the resulting total plasma concentrations of inhibitor that were well above in vitro Ki values. The point estimates and 90% confidence intervals for the ratios of mean midazolam AUC for subjects administered 100 mg RG 12525 (110.6; 98.7-124.1) and 600 mg RG 12525 (98.4; 84.4-114.7) versus midazolam alone were within 80% to 125%. To explain these results, factors that could limit the accuracy of in vitro models in predicting metabolic drug interactions, mainly the high degree of RG 12525 protein binding (> 99.9%), were considered. The lack of correlation between the in vitro inhibition of CYP3A4 by RG 12525 and the inconsequential effects of this compound on midazolam pharmacokinetics accentuate the need to recognize factors other than plasma drug concentrations and potency of in vitro enzyme inhibition when extrapolating in vitro data to predict in vivo drug-drug interactions.

Characterization of 2-[[4-[[2-(1H-tetrazol-5-ylmethyl)phenyl]methoxy]methyl]quinoline N-glucuronidation by in vitro and in vivo approaches.

RG 12525 is a new chemical entity recently evaluated for the treatment of type II diabetes. Clinical studies have previously identified the tetrazole N2-glucuronide conjugate of RG 12525 as the predominant metabolite in plasma following oral administration of RG 12525. Species differences in RG 12525 glucuronidation were first investigated with incubations of RG 12525 with rat, monkey, and human hepatocytes. The results showed the N2-glucuronide to be the major metabolite in human and monkey samples, with only low levels observed for the rat. The formation of this glucuronide by human liver microsomes was subsequently characterized. RG 12525 N2-glucuronidation was found to have a pH optimum of 7.0 to 7.5 and demonstrated a high affinity with a K(m) range of 16.6 to 21.1 microM RG 12525 (n = 3). The rate of N2-glucuronide formation ranged from 2.5 to 15.4 nmol of RG 12525 N2-glucuronide formed/min/mg of protein ( approximately 6-fold) in the 21 samples assayed. The reaction was inhibited by known substrates for glucuronidation, with imipramine (62%), naringenin (44%), and scopoletin (38%) producing the largest degree of inhibition at equimolar concentrations of substrate and inhibitor. Of the eight expressed UDP-glucuronosyltransferase (UGT) forms assayed, UGT1A1 and 1A3 displayed the highest rate of RG 12525 N2-glucuronidation (0.109 and 0.125 nmol/min/mg, respectively). Finally, low levels of N2-glucuronidation of RG 12525 by human jejunum microsomes were demonstrated, suggesting that presystemic clearance via glucuronidation may constitute a barrier to bioavailability.