Ontario Ministry of Natural Resources South-Central Region Bobwhite Quail Rehabilitation Program

Archaeological and historical evidence on status of northern bobwhites (Colinus virginianus) in southern Ontario prior to European settlement is not clear. The bird was documented on the Essex and Kent County prairies at the time of European settlement in the early l700\u27s. Early farmsteading increased available habitat space for quail. That landscape, combined with mild winters in the l 840\u27s, enabled bobwhites to expand their ranges. By the mid-l 850\u27s, bobwhites ranged generally throughout Ontario\u27s tallgrass prairie and savannah communities extending from the Detroit River approximately 300 miles north into Simcoe County, the southeast limit of Georgian Bay, and 400 miles east to Kingston, the eastern limit of Lake Ontario. Bobwhites became a valued upland bird in pioneer Ontario for hunting, viewing and controlling farm garden weed seeds and insects. The detrimental impacts of harsh winters were a major contributor to quail declines from the late l 850\u27s to the l 980\u27s. Additionally, more subtle factors which also contributed detrimental stresses were loss of tallgrass prairie and savannah, intensive agriculture, continued deforestation, urbanization, pesticide use, the taking of wild stock for pen-rearing and the low survival rates of introduced cultured stocks into the wild. In summary, bobwhites in Ontario declined due to the destruction, impairment and fragmentation of wildlife habitat. The population stabilized at low numbers during the early l 980\u27s. Recreational harvesting of the species continued into the l 970\u27s. Gun harvests probably at no time exerted a controlling influence on the quail populations. The harvest diminished to non-existence in the 1980\u27s. The hunting seasons for wild populations were eliminated in the l 990\u27s. People continued to appreciate the bird for recreational viewing and dog training opportunities. In spite of agricultural trends towards less intensive land uses, new emphases on resource and environmental conservation and rehabilitation, as well as milder winters in the l 980\u27s and l 990\u27s, bobwhite numbers have not rebounded in southwest Ontario. Approximately 185 birds in 16 coveys throughout Elgin, Lambton and Middlesex counties were documented in 1990. Although large areas of suitable land are unoccupied by bobwhites, populations remain small, disjunct and isolated. Ontario Ministry of Natural Resources formed partnerships with a number of other governmental agencies, non-governmental organizations and landowners, to initiate the rehabilitation of bobwhite quail in southern Ontario. The Ontario Federation of Anglers and Hunters, their affiliate and individual members, are a key sponsor to this rehabilitation initiative. These groups have participated in an advisory committee, raised funds, and offered volunteer labor, predator control services adjacent to release sites, and professional services. The committee recommended the transfer of wild bobwhites from other North American populations as a means of rehabilitating Ontario populations. The program\u27s goal is to reestablish larger, sustainable populations of quail in southern Ontario to provide recreational viewing and hunting opportunities. It is anticipated that large numbers of urban and rural Ontarians will be pleased with the reestablishment of northern bobwhites and the recreational viewing and hunting benefits they provide. Restoration of quail hunting opportunities will generate economic benefits in Ontario and may be a suitable method for monitoring the grass-shrubland ecotone. Healthy quail populations also have the potential to function as natural control agents for some crop pests

CSF SerpinA1 in Creutzfeldt\u2013Jakob disease and frontotemporal lobar degeneration

Objective: SerpinA1 (alpha-1 antitrypsin) is an acute inflammatory protein, which seems to play a role in neurodegeneration and neuroinflammation. In Alzheimer\u2019s disease and synucleinopathies, SerpinA1 is overexpressed in the brain and the cerebrospinal fluid (CSF) showing abnormal patterns of its charge isoforms. To date, no comprehensive studies explored SerpinA1 CSF isoforms in Creutzfeldt\u2013Jakob disease (CJD) and frontotemporal lobar degeneration (FTLD). Methods: Using a capillary isoelectric focusing immunoassay, we analyzed CSF SerpinA1 isoforms in control cases (n = 31) and patients with a definite or probable diagnosis of CJD (n=77) or FTLD (n = 30), belonging to several disease subtypes. Results: The overall SerpinA1 signal was significantly higher than in controls in CJD subtypes linked to abnormal prion protein (PrPSc) type 1, such as sporadic CJD (sCJD) MM(V)1, and in FTLD-TDP. Moreover, CJD linked to PrPSc type 1 and FTLD-TAU groups showed a significant relative increase of acidic and basic isoforms in comparison with controls, thereby forming two distinct SerpinA1 isoform profiles. Interpretation: CJD linked to PrPSc type 1 and FTLD show a differential upregulation and post-translational modifications of CSF SerpinA1. Further studies are needed to clarify whether these findings may reflect a common, albeit disease-specific, pathogenetic mechanism related to neurodegeneration

Oral Levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial

Objective To evaluate the efficacy and safety of oral levosimendan in amyotrophic lateral sclerosis (ALS) patients. This phase 2, randomised, double-blind, placebo-controlled, crossover, 3-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60-90% of predicted from 11 sites in four countries. Methods Patients received levosimendan 1 mg daily, 1 mg bd or placebo during three 14-day crossover periods, and levosimendan 1-2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale (ALSFRS-R), tolerability and safety. Results Of 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being -3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg bd (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg bd (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events. Conclusions Levosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. A phase 3 study to evaluate the longer-term effects of oral levosimendan in ALS is ongoing

Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis

Objective biomarkers for the clinically heterogeneous adult-onset neurodegenerative disorder amyotrophic lateral sclerosis are crucial to facilitate assessing emerging therapeutics, and improve the diagnostic pathway in what is a clinically heterogeneous syndrome. With non-coding RNA transcripts including microRNA, piwi-RNA, and transfer RNA present in human biofluids, we sought to identify whether non-coding RNA in serum could be biomarkers for amyotrophic lateral sclerosis. Serum samples from our Oxford Study for Biomarkers in MND/ALS discovery cohort of amyotrophic lateral sclerosis patients (n=48), disease mimics (n=16), and age- and sex-matched healthy controls (n=24) were profiled for non-coding RNA expression using RNA-sequencing, which showed a wide range of non-coding RNA to be dysregulated. We confirmed significant alterations with reverse transcription-quantitative PCR in the expression of hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-92a-3p, hsa-piR-33151, TRV-AAC4-1.1, and TRA-AGC6-1.1. Furthermore, hsa-miR-206, a previously identified amyotrophic lateral sclerosis biomarker, showed a binary-like pattern of expression in our samples. Using the expression of these non-coding RNA, we were able to discriminate amyotrophic lateral sclerosis samples from healthy controls in our discovery cohort using a random forest analysis with 93.7% accuracy with promise in predicting progression rate of patients. Importantly, cross-validation of this novel signature using a new geographically distinct cohort of samples from the United Kingdom and Germany with both amyotrophic lateral sclerosis and control samples (n=156) yielded an accuracy of 73.9%. The high prediction accuracy of this non-coding RNA-based biomarker signature, even across heterogeneous cohorts, demonstrates the strength of our approach as a novel platform to identify and stratify amyotrophic lateral sclerosis patients

The use of P300-based BCIs in amyotrophic lateral sclerosis : from augmentative and alternative communication to cognitive assessment

The use of augmentative and alternative communication (AAC) tools in patients with amyotrophic lateral sclerosis (ALS), as effective means to compensate for the progressive loss of verbal and gestural communication, has been deeply investigated in the recent literature. The development of advanced AAC systems, such as eye-tracking (ET) and brain-computer interface (BCI) devices, allowed to bypass the important motor difficulties present in ALS patients. In particular, BCIs could be used in moderate to severe stages of the disease, since they do not require preserved ocular-motor ability, which is necessary for ET applications. Furthermore, some studies have proved the reliability of BCIs, regardless of the severity of the disease and the level of physical decline. However, the use of BCI in ALS patients still shows some limitations, related to both technical and neuropsychological issues. In particular, a range of cognitive deficits in most ALS patients have been observed. At the moment, no effective verbal-motor free measures are available for the evaluation of ALS patients\u2019 cognitive integrity; BCIs could offer a new possibility to administer cognitive tasks without the need of verbal or motor responses, as highlighted by preliminary studies in this field. In this review, we outline the essential features of BCIs systems, considering advantages and challenges of these tools with regard to ALS patients and the main applications developed in this field. We then outline the main findings with regard to cognitive deficits observed in ALS and some preliminary attempts to evaluate them by means of BCIs. The definition of specific cognitive profiles could help to draw flexible approaches tailored on patients\u2019 needs. It could improve BCIs efficacy and reduce patients\u2019 efforts. Finally, we handle the open question, represented by the use of BCIs with totally locked in patients, who seem unable to reliably learn to use such tool

Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALS

Despite major advances in deciphering the neuropathological hallmarks of amyotrophic lateral sclerosis (ALS), validated neurochemical biomarkers for monitoring disease activity, earlier diagnosis, defining prognosis and unlocking key pathophysiological pathways are lacking. Although several candidate biomarkers exist, translation into clinical application is hindered by small sample numbers, especially longitudinal, for independent verification. This review considers the potential routes to the discovery of neurochemical markers in ALS, and provides a consensus statement on standard operating procedures that will facilitate multicenter collaboration, validation and ultimately clinical translation

A cognitive forcing tool to mitigate cognitive bias:A randomised control trial

Abstract Background Cognitive bias is an important source of diagnostic error yet is a challenging area to understand and teach. Our aim was to determine whether a cognitive forcing tool can reduce the rates of error in clinical decision making. A secondary objective was to understand the process by which this effect might occur. Methods We hypothesised that using a cognitive forcing tool would reduce diagnostic error rates. To test this hypothesis, a novel online case-based approach was used to conduct a single blinded randomized clinical trial conducted from January 2017 to September 2018. In addition, a qualitative series of “think aloud” interviews were conducted with 20 doctors from a UK teaching hospital in 2018. The primary outcome was the diagnostic error rate when solving bias inducing clinical vignettes. A volunteer sample of medical professionals from across the UK, Republic of Ireland and North America. They ranged in seniority from medical student to Attending Physician. Results Seventy six participants were included in the study. The data showed doctors of all grades routinely made errors related to cognitive bias. There was no difference in error rates between groups (mean 2.8 cases correct in intervention vs 3.1 in control group, 95% CI -0.94 – 0.45 P = 0.49). The qualitative protocol revealed that the cognitive forcing strategy was well received and a produced a subjectively positive impact on doctors’ accuracy and thoughtfulness in clinical cases. Conclusions The quantitative data failed to show an improvement in accuracy despite a positive qualitative experience. There is insufficient evidence to recommend this tool in clinical practice, however the qualitative data suggests such an approach has some merit and face validity to users

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Relationship of serum beta-synuclein with blood biomarkers and brain atrophy

Background: Recent data support beta-synuclein as a blood biomarker to study synaptic degeneration in Alzheimer's disease (AD). Methods: We provide a detailed comparison of serum beta-synuclein immunoprecipitation - mass spectrometry (IP-MS) with the established blood markers phosphorylated tau 181 (p-tau181) (Simoa) and neurofilament light (NfL) (Ella) in the German FTLD consortium cohort (n = 374) and its relation to brain atrophy (magnetic resonance imaging) and cognitive scores. Results: Serum beta-synuclein was increased in AD but not in frontotemporal lobar degeneration (FTLD) syndromes. Beta-synuclein correlated with atrophy in temporal brain structures and was associated with cognitive impairment. Serum p-tau181 showed the most specific changes in AD but the lowest correlation with structural alterations. NfL was elevated in all diseases and correlated with frontal and temporal brain atrophy. Discussion: Serum beta-synuclein changes differ from those of NfL and p-tau181 and are strongly related to AD, most likely reflecting temporal synaptic degeneration. Beta-synuclein can complement the existing panel of blood markers, thereby providing information on synaptic alterations. Highlights: Blood beta-synuclein is increased in Alzheimer's disease (AD) but not in frontotemporal lobar degeneration (FTLD) syndromes. Blood beta-synuclein correlates with temporal brain atrophy in AD. Blood beta-synuclein correlates with cognitive impairment in AD. The pattern of blood beta-synuclein changes in the investigated diseases is different to phosphorylated tau 181 (p-tau181) and neurofilament light (NfL)